CHAPTER

35

Clinical Reproductive Physiology of the Cow

JEFFREY S. STEVENSON

Reproduction drives the

production cycle in both beef and dairy enterprises and is of major economic consequence. Maximizing the reproductive potential in cattle requires the understanding and application of many principles basic to the various disciplines of animal and veterinary science, including genetics, nutrition,

physiology, and theriogenology, as well as management intervention. This chapter reviews the most current information on the major endocrine and physiologic events that are known to be associated with the onset of sexual maturation or puberty; the physiology of the estrous cycle, pregnancy, parturition, and periparturient period; and the

postpartum transition from anestrus to the onset of estrous cycles. Because of the extent of literature covering these topics, the reader is referred to several key articles and major reviews for further in-depth information.

ONSET OF SEXUAL MATURATION

Increasing reproductive efficiency in beef and dairy herds depends on the timely introduction of replacement

heifers into the breeding herd. Heifers should have their first calf by 2 years of age. Maximizing the proportion of Clinical Reproductive Physiology of the Cow 259 beef heifers that calve early in the calving season leads to heavier calf weaning weights, allows for timely rebreeding, and increases their herd longevity. To maximize lifetime

milk production in a dairy operation, replacements also must calve as 2-yearolds in order to recoup rearing costs. Achieving this goal in either type of production unit requires appropriate heifer development and timely onset of puberty and first conception. Puberty generally is defined as the onset of the first estrus associated with a potentially fertile ovulation that

is followed by a luteal phase of normal duration. Prepubertal heifers may have at least one anovulatory estrus that precedes their first normal cycle (13% to 22% of heifers at an average of 3 months before puberty), often called a nonpubertal estrus. Puberty represents only the onset of sexual maturation, which actually is not achieved until the female reaches the maturity characteristic

of her breed. This is recognized more easily in a litter-bearing species as the time when maximum ovulation rate or litter size is achieved.

Factors Influencing Onset of Puberty The onset of puberty, as well as of nonpubertal estrus, is influenced by several factors, including age, genotype, season, body weight, nutrition, and social rearing environment.1 Genotype

The breed composition of heifers alters age at puberty, because size at puberty is determined genetically. Numerous studies have demonstrated differences in age and weight at puberty among various breeds. In general, European (Bos taurus) dairy and beef breeds attain puberty earlier than do those of Zebu origin (Bos indicus). Breed of sire and dam alters age at puberty, and crossbreeding reduces age at puberty in heifers.

Although timing of puberty is altered by many factors, as discussed later, age at puberty is influenced by selection. Breeds selected for milk production as well as for size (dairy and beef breeds) reach puberty earlier than do breeds of similar mature size and retail product growth potential but not selected for milk yield. Inbreeding delays puberty in heifers by retarding rate of growth. Estimates of heritability for age at puberty range from

0.41 to 0.64, two- to threefold higher than the estimates of heritability of milk production. With such relatively high heritabilities, practices of selection for earlier puberty in genotypes with traditionally later sexual development could prove beneficial, particularly in some beef breeds in which puberty often is delayed. Heifers sired by

bulls with large scrotal circumferences reach puberty at younger ages and rebreed sooner after their first parturition than do heifers sired by bulls with small scrotal size. Studies also have demonstrated that heifers that are heavier at 6 months of age (before puberty) reach puberty at younger ages and also are heavier at calving. Although beef heifers that are heavier at weaning reach puberty at

younger ages, these same heifers experience longer intervals to estrus after their first parturition than do their lighter-weight contemporaries. Season Although cattle are not considered to be seasonal breeders, evidence indicates that season of birth may alter timing of puberty. When heifers were fed similarly in controlled environmental chambers, those born in the

autumn reached puberty earlier than those born in the spring.2 Heifers born late within a spring calving season, however, were younger and lighter at puberty, probably because of improved forage quality and its effects on milk availability from their dams and digestibility of forages obtained by their grazing. Body Weight and Nutrition Although age and weight are correlated somewhat with

the onset of sexual maturity, body weight is the major factor affecting age at puberty in cattle. Generally, the onset of puberty occurs when the heifer reaches approximately 40% to 50% of her mature weight. Unintended pregnancies may be initiated in heifers younger than 6 months of age when they are maintained in the presence of breeding bulls. Initiation of puberty normally occurs

in yearling heifers, but age at puberty may range from 4 months to more than 2 years. Puberty is delayed in heifers that are maintained on low planes of nutrition during the prepubertal growth phase. Onset of puberty is dictated by body weight for the breed. Although age at puberty is influenced by nutritional factors, body weight at puberty is unaffected by nutrition. Correlations between gain in

body weight and age at puberty indicate that increased growth rate of heifers results in younger age at puberty. In short, heifers on various planes of nutrition will reach puberty at different ages, but at similar relative stages of physical development. Furthermore, subsequent adequate weight gains are required once heifers reach puberty to ensure that they continue to have normal estrous cycles.

Underfeeding or overfeeding heifers has significant consequences on their development. Underfeeding of growing heifers may result in delayed puberty, subnormal conception rates, underdeveloped mammary glands, and greater incidence of calving problems.3 Overfeeding often results in weak expression of estrus, subnormal

conception rates, high embryonic mortality, decreased mammary gland development, and reduced milk production. 3 Dairy heifers fed 115% of all 1989 National Research Council nutrient requirements for heifers to gain 0.7 kg/day from 3 to 24 months of age were younger at puberty, were heavier at calving, had larger heart girth, were longer, were not excessively fat at calving, and

calved at younger ages. Nutrient requirements suggested by the National Research Council should serve as minimum guidelines. Social Rearing Environment In some feral mammalian species, the physical presence of the male decreases age at puberty in contemporary females. Presence of mature bulls and adult cycling cows has altered age at puberty of heifers in some but not all

studies. Increased proportions of prepubertal beef heifers treated oronasally with bull urine reached puberty earlier than water-treated controls.3 260 CHAPTER 35

Endocrine Mechanisms The events necessary to initiate the first pubertal estrus occur by an organized and interdependent cascade of changes in the central nervous system, hypothalamus,

pituitary, and ovaries during maturation.4 These events are summarized in Figure 35-1. As early as 4 months of age, the pituitary is capable of releasing luteinizing hormone (LH) in response to injections of gonadotropinreleasing hormone (GnRH). Likewise, the ovaries respond to exogenous and endogenous (GnRH-induced) gonadotropins by increasing the production of ovarian steroids.4

Early ovarian follicular development is evident. In fact, intrarectal ultrasonography shows that groups of follicles develop in regular repeating patterns (waves), beginning as early as 2 weeks of age, similar to what is observed in adult females during the estrous cycle and pregnancy4 (see discussion of follicular dynamics below). The largest follicle, or dominant follicle, within each follicular wave

of developing follicles progressively increases in maximal diameter from 2 to 34 weeks of age, parallel to increasing numbers of follicles detected in each follicular wave.4 The combined evidence of early established pituitary and ovarian competence suggests that hypothalamic inactivity (lack of GnRH pulses secreted into the hypophyseal

portal vessels) is responsible for maintaining the prepubertal status. The mechanism by which the hypothalamus remains relatively inactive has not been elucidated in cattle. Maturation of the GnRH pulse system (pulse generator) in the hypothalamus may necessitate other central nervous system involvement. Increased hypothalamic turnover and decreased sensitivity to various

neurotransmitters occur in rodents as puberty is imminent. Specifically, increased turnover of norepinephrine and dopamine normally accompanies pulses of LH in the rat. Endogenous opioids may be involved in inhibiting the requisite LH pulse frequency, because administering an opioid receptor antagonist (naloxone) to 4week-old

heifers induced LH pulses, with the response decreasing as heifers approached 32 weeks of age.4 Evidence in ewes and heifers suggests that the prepubertal GnRH pulse generator is highly sensitive to the negative feedback of ovarian estrogens, such that estradiol inhibits secretory pulses of LH and probably those of GnRH as well (see Fig. 351). This phenomenon was

described earlier in rats and is known as the gonadostat theory of puberty.4 This theory suggests that the threshold to the negative feedback of estrogen increases as puberty approaches, accounting for a decreased sensitivity of the hypothalamus to the negative feedback of estrogen. Thus, the inhibitory mechanism modulating pulsatile release of GnRH and LH decreases, resulting in

an increasing frequency of pulses, which normally are observed as puberty approaches (see Fig. 35-1). The pulse frequency of LH gradually increases between day 126 and day 14 before puberty, whereas concentrations of estradiol receptors within the hypothalamus decline. ____ Estradiol secretion Estradiol

feedback GnRH secretion LH secretion Follicle diameter Prepubertal Peripubertal Puberty Fig. 35-1 Conceptual model for endocrine changes responsible for the onset of puberty in heifers. The peripubertal period includes approximately the 50 days preceding puberty in heifers.

The sign within the arrows representing estradiol feedback indicates negative () or positive (+) feedback on secretion of luteinizing hormone (LH), and width of the arrows indicates relative degree of negative feedback. Secretion of gonadotropin-releasing hormone (GnRH) is highly sensitive to estradiol negative feedback during the prepubertal period. As the peripubertal period and the associated decline in estradiol negative

feedback begins, secretion of GnRH, and hence LH, increases resulting in increased growth and estradiol secretion by dominant ovarian follicles. As a result of the progressive decline in estradiol negative feedback and increase in LH pulse secretion during the peripubertal period, estradiol eventually attains concentrations sufficient to induce the pubertal preovulatory surge of LH. (From Day ML, Anderson LH: Current concepts

on the control of puberty of cattle. J Anim Sci 1998;76:1 Suppl3.) Clinical Reproductive Physiology of the Cow 261 Endogenous LH pulses occur at a frequency of one to four per 24 hours during the prepubertal period. As during the estrous cycle, the frequency of LH pulses sufficient to drive follicular maturation to ovulation must increase to approximately one pulse per hour. For 3 weeks

before puberty, blood concentrations of progesterone seldom rise above 0.5ng/ml (indicative of significant luteal tissue in the ovaries and little or no negative feedback of progesterone on LH secretion). Therefore, the frequency of LH pulses seems to be insufficient to support follicular maturation and ovulation during this period.4 The transition into puberty occurs for 2 to 4 weeks

before first ovulation. This transient stage is characterized by an increased frequency of LH pulses and ovulation, as determined by a significant increase in blood concentrations of progesterone. In most cases, heifers in this transitional period exhibit one or two short-lived (duration of 2 to 5 days) elevations in blood progesterone of lower magnitude than what is observed in the normal estrous

cycle. These transient increases in progesterone are preceded by LH pulses, the source of which may be luteinized ovarian follicles, and may be involved in preparing the uterus for the possibility of pregnancy and/or the establishment of normal patterns of GnRH and LH pulses characteristic of cycling females. The first major preovulatory LH surge occurs only after earlier prepubertal rises in

progesterone, with a behavioral estrus observed in some heifers at this time. Puberty has been induced by administering a progestin as an ear implant containing norgestomet for 9 days,3 in addition to an intramuscular injection containing both norgestomet and estradiol valerate, or as a progesterone-releasing intravaginal insert. Similar success has been reported when melengestrol

acetate was fed for 7 to 16 days.3 The effectiveness of these treatments depends on attainment of adequate body weight in heifers, characteristic of that necessary at normal puberty for their genotype.

PHYSIOLOGY OF THE ESTROUS CYCLE General Traits

Once puberty occurs, estrous cycles generally continue unabated unless pregnancy is established or nutritional

conditions are limited severely. Estrous cycles typically are 3 weeks in duration but normally may range from 17 to 25 days. The period of estrus may range from 2 to 50 hours in duration but averages 12 to 18 hours under most conditions. Ovulation occurs approximately 24 to 30 hours after the onset of estrus, with the first signs of estrus

usually coinciding with the beginning of the preovulatory surge of LH and folliclestimulating hormone (FSH). Durations of estrous cycles are often 1 to 2 days shorter in heifers than in cows. High seasonal temperatures do not seem to alter duration of cycles but may reduce the duration of estrus and decrease blood flow to the reproductive tract and may alter concentrations of various reproductive hormones.2

The estrous cycle is divided into two distinct phases follicular (day 19 until estrus occurs) and luteal (days 1 to 18)or into four stages estrus (day 0), metestrus (days 1 to 3), diestrus (days 4 to 18), and proestrus (day 19 until behavioral estrus occurs). Estrus is characterized by sexual receptivity of the female (standing behavior) to a bull or to mounting activity by other females, in addition to follicular growth in preparation for ovulation.

Metestrus is characterized by final follicular maturation and ovulation, formation of the early corpus luteum, and its subsequent ability to secrete progesterone. Once significant concentrations of progesterone are observed in peripheral blood, the luteal phase or period of diestrus begins and continues until the corpus luteum starts to regress at the onset of luteolysis. As concentrations of

progesterone in blood begin to decline rapidly with the demise of the corpus luteum, the follicular phase is initiated, leading to the selection and accelerated growth of another ovulatory follicle. Some important differences in these basic traits of estrus have been observed between Bos taurus and Bos indicus breeds. Specifically, Bos indicus females are reported to have periods of estrus of shorter duration, shorter intervals from the onset of estrus to ovulation,

reduced magnitude of the preovulatory concentration of the LH surge, smaller corpora lutea, and lower lutealphase concentrations of progesterone.1,3

Endocrine Patterns For purposes of describing the interactions of hormones secreted by the hypothalamus, pituitary, ovaries, and uterus that are involved in the orchestration of sexual

behavior and normal endocrinology of the estrous cycle, the cycle can be divided into three endocrine periods: (1) pregonadotropin surge, (2) postgonadotropin surge, and (3) luteal phase.5 Pregonadotropin Surge The period of the pregonadotropin surge begins with the demise of the corpus luteum and ends with the preovulatory surge of LH and FSH, which initiate ovulation of a

mature follicle 24 to 30 hours later (Fig. 35-2). Concentrations of progesterone rapidly decline as those of estradiol begin to increase concurrently with the accelerated growth of the preovulatory follicle. As progesterone declines, the baseline concentration of LH increases,5 the frequency of LH pulses increases from about one pulse

every 4 to 6 hours to one pulse every hour, but the amplitude of LH pulses declines5 (all because of reduced negative feedback by progesterone on the hypothalamus and pituitary). This change in LH secretion, which coincides with a parallel pulsing of estradiol secreted into the venous effluent of the ovary bearing the preovulatory follicle, can be monitored in jugular blood by frequently collected blood samples (see Fig. 352). Although follicular

growth may be stimulated by FSH alone, a combination of LH and FSH has been shown to induce maximal synthesis of estradiol in vitro.6 Thus, both gonadotropins influence follicular development and subsequent secretion of estradiol. Estradiol appears to exert inhibitory effects on FSH release, because when it is administered to ovariectomized heifers, FSH is reduced to precastration

concentrations. Furthermore, when titers of estradiol are 262 CHAPTER 35 at their peak just before the preovulatory surge, concentrations of FSH are lowest.5 A carefully orchestrated cascade of increasing LH pulses and elevated titers of estradiol eventually culminates in the onset of estrus, with estradiol triggering the initiation of both estrous behavior and the preovulatory

surge of LH (see Fig. 35-2). Estradiol apparently triggers more frequent pulsatile GnRH secretion by the hypothalamus and enhanced pituitary responsiveness to each priming GnRH pulse. Blocking the rise in estradiol by chemical or immunologic means can block the occurrence of the gonadotropin surge.5 Likewise, concentrations of progesterone must be low before estradiol can

induce the gonadotropin surge, because administering progesterone during the period before the surge can block it. The elevation of LH and FSH (surge) usually endures for 8 to 10 hours. Termination of the surge is due to refractoriness of the pituitary to GnRH (decreased concentration [down-regulation] of pituitary GnRH receptors) and depletion of the releasable pool of pituitary

gonadotropin. This hypothesis is substantiated by two observations: (1) When heifers are ovariectomized shortly after the onset of estrus and the preovulatory surge, a delay in the classic postcastration rise in LH is observed, and (2) injections of GnRH within 12 to 16 hours of the onset of the surge result in the release of only marginal amounts of gonadotropin. Postgonadotropin Surge

The postgonadotropin surge period is characterized by declining titers of estradiol in blood, after their peak at the onset of estrus, as follicular luteinization ensues (Fig. 35-3). The process of ovulation has been likened to mechanisms associated with an inflammatory reaction.7 The process of follicular rupture is regulated by a host of intrafollicular mediators. For example, ovulation can be blocked by intrafollicular administration of various

prostaglandin enzyme inhibitors or antiserum to various prostaglandins or their regulatory enzymes.5 Inter theca cell capillaries and the basement membrane of the follicle are disturbed at ovulation, accounting for some hemorrhage, and thus allowing both capillaries and theca cells to pervade the ruptured follicle. Follicular content of estradiol declines rapidly as progesterone content

begins to increase, because both theca and granulosa cells differentiate into luteal cells (luteinize) that form the corpus luteum. Theca cells appear to develop into smaller-diameter cells, known as small luteal cells, and the granulosa cells become large luteal cells as the corpus luteum develops.8 2 Hours 04 2

Hours 04 2 Hours 04 E2 LH E2 LH E2 LH Onset of estrus Onset of ovulation

E2 P4 LH 27 hr Estrus Fig. 35-2 Concentrations of progesterone (P4), estradiol (E2), and luteinizing hormone (LH) during the pre- and postgonadotropin surge period of the bovine estrous cycle. During diestrus (because of high concentrations of progesterone secreted by

the corpus luteum), the frequency of LH pulses in jugular blood is low (approximately one per every 4 to 6 hours) and pulse amplitude is high, similar to that of estradiol in the ovarian venous effluent. As the corpus luteum dies and progesterone declines to baseline concentrations, the pulse frequency of LH increases to approximately one per hour (decreased amplitude) followed by correlated secretion of estradiol.

The LH surge results from increased LH pulse frequency sufficient to sustain a peak (surge) of 8 to 12 hours induced by maximal titers of estradiol. These two events are coincident with the onset of estrus, which is followed by ovulation in approximately 27 hours. Clinical Reproductive Physiology of the Cow 263 The remainder of what is called metestrus (days 1 to 3) is characterized by low blood concentrations of LH,

estradiol, and progesterone (see Fig. 35-3). A secondary rise in FSH of lower magnitude than that observed during the surge often is reported just before ovulation, or about 24 to 30 hours after the onset of the preovulatory surge. This secondary rise may be a consequence of the loss of follicle-derived inhibin production during the ovulatory process. This increase in FSH probably is critical

to the recruitment of the first wave of antral follicles that becomes visible by intrarectal ultrasonography during early metestrus11 (see Fig. 35-3; see also subsequent section on follicular dynamics). Luteal Phase The luteal phase (days 4 to 18) begins when the corpus luteum secretes significant concentrations of progesterone, which generally exceed 1 ng/ml by day 4 or 5 of

the cycle (see Fig. 35-3). As progesterone establishes itself again as the dominant negative feedback hormone of the luteal phase, patterns of LH secretion are modified once again to a lower frequency (one pulse every 4 to 6 hours) but with higher-amplitude pulses. Progesterone reaches maximal concentrations by days 8 to 10, which is nearly

coincident with the maximum weight of the developing corpus luteum. Both cell types of the corpus luteum secrete progesterone, but the small luteal cells seem to have nearly all of the LH receptors and are six times more responsive to LH in vitro than the large luteal cells in terms of progesterone secretion.8 The small luteal cells represent about 20% of the total luteal cell population

and contribute approximately 15% of the progesterone secreted by the corpus luteum, whereas the remainder is derived from the large luteal cells. The large cells, however, have nearly all of the receptors for prostaglandin E2 (PGE2) and prostaglandin F2 (PGF2). Concentrations and affinity of highly specific PGF2 receptors in the bovine corpus luteum are similar on days

2, 4, 6, and 10 of the estrous cycle, failing to explain the lack of luteolytic response of the corpus luteum to PGF2 before day 5 or 6 of the cycle. Large luteal cells also produce neurophysin and oxytocin, identical to those produced in the hypothalamus and stored in the posterior pituitary.8 Early in pregnancy, about 20 days after conception, the original large cells disappear, leaving

the small luteal cells, some of which expand into largerdiameter luteal cells in the corpus luteum of pregnancy.8 The major luteotropin in cattle is thought to be LH, because if antiserum to LH is administered during the luteal phase, regression of the corpus luteum ensues. Marked pulses of PGF2 secreted by the uterus, in absence of a viable embryo, cause regression or death of the corpus luteum, thereby ending the luteal phase (see

Fig. 35-3). After about 14 days under the influence of progesterone secretion, the endometrium secretes pulses of PGF2, each lasting about 6 hours, for a total of approximately 36 hours. Prostaglandin F2 causes an immediate decline of progesterone and oxytocin to basal concentrations within 6 to 10 hours in the peripheral circulation and in the content of the corpus luteum. Uterine involvement

in the process of luteolysis is supported by the prolonged maintenance of the corpus luteum when the uterus is removed during the luteal phase. Furthermore, cattle with a congenitally absent uterine horn that is ipsilateral to the ovary bearing the corpus luteum have prolonged cycles with an extended luteal lifespan. Such observations, as well as surgical preparations in sheep,

have provided evidence of a local utero-ovarian control of luteal lifespan. Current observations suggest that PGF2 produced by the uterine horn adjacent to the ovary bearing the corpus luteum is transferred from the uterine venous effluent into the ovarian artery via a countercurrent transfer mechanism. Some controversy remains concerning the mechanism by which PGF2 induces luteolysis. Luteolytic effects of

PGF2 are thought to occur in part through its direct interPGF2_ E2 0 5 10 15 21 Days of the bovine estrous cycle Ovulation Ovulation Metestrus Estrus Estrus Diestrus Proestrus FSH LH

Fig. 35-3 Diameters of two dominant follicles and their respective subordinate follicles from each of two cohorts of follicular waves during the bovine estrous cycle. Peak concentrations of folliclestimulating hormone (FSH) are detected 1 to 2 days before the recruitment of each follicular wave. The first peak is nearly coincident with ovulation during metestrus. During diestrus,

when elevated concentrations of progesterone (P4) are secreted by the corpus luteum, pulses of luteinizing hormone (LH) are sufficient to allow selection of dominant follicles but insufficient to allow maturation of a dominant follicle until progesterone returns to basal concentrations after spontaneous luteolysis (increased uterinesecreted prostaglandin F2 [PGF2]) or in

response to exogenous injections of PGF2. After luteolysis, during proestrus, LH pulse frequency and estradiol (E2) increase sufficiently to induce behavioral estrus and the LH surge. (Adapted from Thatcher WW: Fundamentals of dairy reproduction. The 100-day contract: Fundamentals for achieving reproductive efficiency CD-ROM. Pharmacia Animal Health, Kalamazoo, MI.)

264 CHAPTER 35 vention with luteal cells and, indirectly, via a reduction in luteal blood flow. Although PGF2 has vasoconstrictive properties, it has not been determined whether the marked decrease in ovarian and luteal blood flow that occurs in spontaneous or PGF2-induced luteolysis is a cause or consequence of luteolysis. Recent evidence indicates that luteal oxytocin is involved in luteolysis, probably

through its ability to elaborate more secretion of PGF2 from the endometrium as the corpus luteum begins to regress and oxytocin is released during luteal demise. Oxytocin given exogenously on days 5 to 8 of the cycle causes regression of the corpus luteum only if the uterus is present.5 Estradiol produced by the dominant large follicle late in the cycle is thought to initiate the process of

luteolysis by inducing production of uterine PGF2. Estradiol induces uterine endometrial receptors for oxytocin, which, when occupied by oxytocin, activate phospholipase A2 and release arachidonic acid and the arachidonic acid cascade, leading to production of uterine PGF2 and eventual luteolysis. Administration of exogenous estrogens initiates luteolysis and can stimulate uterine production

of PGF2. Conversely, removal of ovarian follicles after day 10 of the cycle will extend luteal function for several days beyond the duration of a normal cycle. Therefore, the positive feedback cascade of oxytocin from the corpus luteum to the uterus and of PGF2 from the uterus to the corpus luteum probably serves as a fail-safe mechanism to ensure luteolysis. The process of luteolysis and actions of PGF2 can be monitored by measuring a

major blood serum-stable metabolite of PGF2, 15-keto13,14-dihydro-PGF2 (PGFM). Luteolytic pulses of PGF2 (peripheral PGFM) are observed with concurrently detectable increases in estradiol and declining concentrations of progesterone (see Fig. 353).

Follicular Dynamics Waves of follicular growth develop throughout the bovine estrous cycle. In each cycle, either two, three, or

four waves of follicular growth can occur, with two waves being most common in adult cows.6,9 An example of one cow with two follicular waves is illustrated in Figure 35-3. Each wave consists of a cohort of follicles that begin to increase in diameter from their original 1- to 2-mm size (recruitment), the largest of which becomes the dominant follicle by continuing to grow (selection), whereas others

degenerate and undergo atresia.9 Once dominant, the dominant follicle undergoes three phases of development: growth (increasing diameter); stasis (little change in diameter); and regression (decreasing diameter [atresia]). The first wave consistently begins around day 1 of the cycle. The second, third, and fourth waves begin at more variable times, with more waves occurring in

cows with longer estrous cycles. Any dominant follicle can mature and ovulate, if the corpus luteum is forced to regress by exogenous injections of PGF2 at the appropriate time. In other words, if PGF2 were given and the corpus luteum regressed during the growing or early static phase of the dominant follicle, it could proceed to ovulation. Otherwise, if the dominant follicle has begun to

become atretic, a new dominant follicle will develop from a new cohort of follicles, accounting for a longer follicular phase.9 In retrospect, atretic follicles can be identified histologically by the presence of pyknotic nuclei in the granulosa cell layer or by the decreased ratio of estrogen to progesterone in the follicular fluid. Emergence of each follicular wave is initiated by an

increase in FSH9 (see Fig. 35-3). The first wave is initiated by the secondary rise in FSH that follows its preovulatory surge. All other waves are initiated by detectable transient increases in FSH that precede the ultrasonographic appearance of each wave by 1 to 2 days. Increased estradiol in blood is observed shortly thereafter, as the largest follicle becomes dominant and estrogenic.9 The largest

follicle apparently dominates its subordinate cohort of follicles by producing various substances, including inhibin. Because of this orchestrated regular occurrence of follicular waves, at least one dominant follicle (codominance of two large follicles can occur) is always present in the pair of ovaries at any stage of the cycle. This phenomenon guarantees great difficulty in accurate prediction

of stage of the cycle or impending estrus by palpation of the ovaries alone, even when a palpable corpus luteum is identified. Accurate diagnosis of a functional corpus luteum by palpation per rectum is difficult. Studies in which the presence or absence of functional luteal tissue was validated by concurrent measurement of progesterone

in serum indicated that when a corpus luteum was identified by palpation, only 82% of the time was its presence validated by high concentrations of progesterone. When a corpus luteum was not palpated, progesterone concentrations were low 70% of the time, indicating that a corpus luteum was present but missed in 30% of the cases. Follicular maturation follows coordinated actions of

LH and FSH through receptors in theca and granulosa cells, respectively (Fig. 354). LH binds to theca cells and stimulates production of androgens, which subsequently diffuse through the basement membrane and into granulosa cells. Binding of FSH to granulosa cells increases aromatase activity, which converts androgens to estradiol.

Increasing concentrations of estradiol and FSH also up-regulate receptors for LH in granulosa cells in maturing preovulatory follicles (<10mm in diameter). Binding of LH and FSH by granulosa cells is necessary for regulating final follicular maturation and eventual ovulation in response to these hormones.6 These two cell types

and the associated gonadotropins are regulated by finely tuned mechanisms because estradiol also can inhibit the production of progesterone in both theca and granulosa cells, thus ensuring that androgens are produced via a parallel enzymatic pathway in both cell types (see Fig. 35-4). This system of regulation of theca and granulosa cells by LH and FSH often is referred to as the two-cell, two-gonadotropin model.6,8

PREGNANCY
Pregnancy is defined as the period from fertilization until parturition. Gestation in cattle is approximately 280 days in duration, with a normal range of 270 to 292 days. Variability in the duration of pregnancy is influenced by fetal sex; number of fetuses; breed; genotype of the sire, dam, or fetus; plane of nutrition; and environmental factors.1

Clinical Reproductive Physiology of the Cow 265 Male fetuses are carried longer than female fetuses, whereas presence of twin fetuses results in shortened periods of gestation. Undernutrition and heat stress can shorten gestation, retard fetal growth, and result in weak calves. If conception occurs at a given estrus, blood or milk

concentrations of progesterone rise within 3 to 4 days, as in the normal cycle. Instead of declining at about day 17 or 18, however, they remain elevated for the duration of pregnancy (Fig. 35-5). The functionality of the corpus luteum must be spared (i.e., luteolysis must be prevented) to allow pregnancy to continue. Progesterone stimulates the glandular epithelium of the endometrium to proliferate

and become secretory (histotroph or uterine milk), providing the only source of nutrients for the growing conceptus before placentation occurs and a minor portion even afterward. In addition, progesterone decreases uterine tone and myometrial contractility by increasing the threshold of sensitivity to various myometrial stimulants, thus allowing free expansion of the conceptus and placenta without expulsion from the uterus.

Maternal Recognition of Pregnancy At about day 16 or 17, the conceptus appears to signal its presence to its dam, an event known as maternal recognition of pregnancy.10 The timing of this recognition was determined by an experiment in which embryos were transferred into the uterus at various times; it was (_)

(_) (_) (_ (_) ) Theca cell Granulosa cell Estradiol-17_ (blood) Estradiol-17_ (follicular fluid) Follicle basement membrane Cholesterol Cholesterol Pregnenolone Pregnenolone Progesterone Androstenedione Estradiol-17_

Testosterone Progesterone LH FSH LH Fig. 35-4 Suggested twocell, two-gonadotropin model for regulation of estradiol by preovulatory follicles. Theca cells provide androgen precursors in response to luteinizing hormone (LH) stimulation of cholesterol (derived mostly from lowdensity lipoprotein [LDL]cholesterol) conversion

to pregnenolone and androstenedione. Androstenedione crosses the basement membrane into the granulosa cells and is converted to testosterone in response to folliclestimulating hormone (FSH) in small follicles and in dominant follicles in response to LH. Increased supply of testosterone leads to synthesis of estradiol, which is transferred into the follicular fluid or back across the basement membrane to increase blood

concentrations of estradiol. Concentrations of estradiol inhibit the conversion of pregnenolone to progesterone in both follicle cell types. _10 _5 0 5 10 Days from parturition 10 Weeks of gestation 0 20 30 40 PRL E2 E1 PGFM Relaxin

P4 Fig. 35-5 Upper panel, Concentrations of progesterone (P4) and estradiol (E2) during gestation in the bovine. Lower panel, Relative acute changes in various hormones during late gestation before parturition are illustrated: P4, E2, estrone (E1), relaxin, prolactin (PRL), and 15-keto13,14-dihydro-PGF2 (PGFM). 266 CHAPTER 35

observed a viable embryo must be present in the uterus by day 16 or 17 to prevent luteal demise. If the embryo dies before day 16, then the cow will recycle in 18 to 24 days, as if conception never occurred. If the embryo dies after the demise of the corpus luteum is prevented, then the cow may have a delayed return to estrus (prolonged cycle). Up until this time, the hormones of the estrous

cycle and pregnancy are effectively similar (see progesterone [P4] and estradiol [E2] in Figs. 35-3 and 35-4), and changes in the oviductal and uterine environments occur regardless of pregnancy status. Beyond this point, a viable conceptus in the uterus plays an active role in securing its survival there. Consequently, luteal maintenance,

which is characteristic of pregnancy, reflects responses of the uterus and ovary to physiologic conditions initiated by one or more signals from the conceptus and its products. Several hypotheses have been presented to explain the mechanism by which the embryo signals its presence and prevents luteolysis.10 The embryo actively secretes a host

of steroids, prostaglandins, and proteins into the lumen of the uterus beginning on day 13. Between then and day 16 or 17, noticeable conceptus-altered maternal physiology is not observed, but during this critical period, the normal cycle of events associated with luteal regression is modified to accommodate the existing pregnancy. Embryos may produce an antiluteolytic substance that

prevents luteolysis either directly or indirectly by inducing a uterine luteotropic substance. Prostaglandin E (PGE), when infused directly into the uterus beginning in the late luteal phase of the estrous cycle, has delayed luteolysis in some experiments. Furthermore, administering homogenates of day 10 to 12 bovine embryos into the uterine lumen also has delayed luteolysis.10 Experiments

have demonstrated that bovine blastocysts (obtained at days 13 to 19) produce progesterone, testosterone, estradiol, PGE, and PGF2. A bovine-produced conceptus protein known as interferontau may signal changes in endometrial production of various prostaglandins in the presence of the embryo, thereby preventing luteolysis and maintaining the corpus luteum.10 Therefore, the embryo probably produces a luteotropin that prolongs

luteal life span. Around days 10 to 12 of the cycle or pregnancy, blood flow to the ovary bearing the corpus luteum increases markedly and remains elevated throughout pregnancy.5,8 Presence of the ovary bearing the corpus luteum is essential to maintain pregnancy in the cow until about day 200 of gestation. In one study, nearly all pregnant cows that were subjected to bilateral ovariectomy maintained

their pregnancy, so long as their adrenal glands remained intact. Elevated concentrations of progesterone and placental estrogens during pregnancy inhibit pituitary LH secretion sufficiently to prevent a preovulatory surge of LH and ovulation (see Fig. 35-5). Continuing patterns of follicular waves into pregnancy have been reported, however.9

Hormonal Patterns

The fetoplacental unit secretes estrone (E1) (see Fig. 35-5), which becomes sulfated and increases throughout pregnancy in conjunction with fetoplacental growth and development. Estrone and estradiol produced by the fetoplacental unit are conjugated immediately by the placentomes to prevent excessive estrogenic effects on

maternal tissues. The conjugated estrogens (estrone sulfate) are pooled in the fluids of the chorioallantois and amnion of the placenta and in maternal circulation. A gradual increase in conjugated and free estrogens (1% to 10% of conjugated forms) occurs during pregnancy, beginning by day 60 of gestation. In addition, during the last 2 months of pregnancy, the placenta may be capable

of maintaining pregnancy by its de novo synthesis of progesterone and estrogen.1 Concentrations of estrogen increase markedly during the last 1 to 4 weeks of gestation (see Fig. 35-5). Other steroids also appear to be synthesized in the placenta but are depleted immediately after birth of the calf and expulsion of the placenta. During the latter few weeks of gestation, various

changes in ovarian and placental secretions occur (see Fig. 35-5). In addition to the changes in ovarian and placental steroids discussed above, concentrations of relaxin are increased by secretions of either the corpus luteum or the placenta to prepare the cervix, uterus, and pelvic ligaments for fetal expulsion. Similar changes in maternal concentrations of PGFM and prolactin (PRL). The peak in

PRL occurs just before parturition, to initiate lactogenesis. If this peak is blocked by various drugs, milk yield after calving is suppressed severely.

PARTURITION
Pregnancy is terminated by the fetus once it is capable of surviving outside the uterus. The specific mechanisms differ slightly between species, but in general, the hormonal changes associated with parturition are those

involved with final maturation of the fetus, termination of pregnancy, expansion of the birth canal, initiation of uterine contraction, maternal behavior, synthesis of milk, and the ability to eject milk. The signal to initiate parturition appears to reside in the hypothalamic-pituitary axis of the fetus (Fig. 356).11 Thus, surgical removal of the fetal pituitary or adrenal

glands prolongs gestation. Adrenocorticotropic hormone (ACTH) administration to fetuses causes premature birth, as does injection of cortisol or its synthetic analogues to the dam. Increased cortical growth in fetal adrenal glands during late pregnancy occurs in the absence of noticeable elevations in fetal ACTH. Recent work indicates that production of prostanoids within the fetal brain influences

fetal ACTH secretion and that induction of prostanoid biosynthesis near the end of gestation may be important in the process of parturition.11 Fetal ACTH becomes elevated 1 to 2 days before birth, coincident with increases in corticosteroids, however.11 The target for the fetal cortisol, which results from ACTH release or uteroplacental transfer of cortisol given

to the dam, is the placenta. The rise in fetal corticosteroids during the last month of gestation is responsible for activation of enzymes in cotyledons that increase the conversion of progesterone to estrogens or their precursors. 11 Such an increase in placental steroidal activity is evidenced by the dramatic rise in prepartum concentraClinical Reproductive Physiology of the Cow 267

tions of estrogens, estrone sulfate, and other estrogen precursors (see Fig. 35-5). Estrogen and androgens secreted by the placenta augment activity of the fetal hypothalamicpituitary-adrenal axis by increasing fetal ACTH secretion and by decreasing negative feedback sensitivity to cortisol.11 In sheep, cortisol can stimulate the ratelimiting enzyme 17-hydroxylase, causing the placenta

to secrete predominantly estrogen, rather than progesterone.11 Progesterone in maternal blood declines gradually during the last week, before falling rapidly to baseline concentrations at parturition (see Fig. 35-5). The gradual decline in progesterone may be due partly to increased placental metabolism of progesterone to estrogens or their precursors. Estrogen, in turn, stimulates release of maternal PGF2 from the uterine endometrium (see Fig.

35-5), resulting in the regression of the corpus luteum of pregnancy. Estrogen also induces receptors for oxytocin, thus preparing the uterus for parturition by oxytocininduced contractions. Prostaglandin F2 induces release of oxytocin from the posterior pituitary, and both hormones act as smooth muscle simulators to elaborate contraction

of the myometrium and expel the fetus.1,11 Furthermore, PGF2, estrogen, and relaxin cause softening of the cervix and relaxation of the pelvic ligaments to facilitate birth. Although much of the foregoing discussion has been proved experimentally, some details remain elusive at present and need to be documented.

PUERPERIUM AND POSTPARTUM PERIOD

After parturition, the cow enters a variable period of sexual quiescence or lactational anestrus before cyclic ovarian activity resumes. Although numerous factors probably interact to affect the duration of the postpartum anestrus, including breed and age of cow, milk yield, nutritional status, body condition, season, and presence of bulls, the presence (in beef cows) or absence (in dairy

cows) of suckling seems to be the key inhibitor of estrous cycles.

Puerperium Involution of the previously gravid uterus is another critical event that must occur during the early postpartum period.12 The rate of involution is somewhat remarkable, because by 20 days after calving, tissue sloughing and hemorrhage have ceased, and the size of the uterus has

been reduced by more than 80%. By 40 days, the uterus has completely involuted except for isolated pockets of Hypothalamus Hypothalamus Posterior pituitary gland Anterior pituitary gland Fetal adrenal cortex Gravid

uterus Myometrium (contraction and delivery) Cervix (softening) Relaxin CRF ACTH PGF2_ (_) Glucocorticoids Placenta Progesterone (_) FETAL

MATERNAL Estrogens (_) Oxytocin (_) Fig. 35-6 A suggested sequence of fetal and maternal events leading to and associated with parturition in cattle. The time of parturition is controlled by maturation of the hypothalamicpituitaryadrenal axis in the bovine fetus. Fetal corticotropinreleasing factor (CRF) is secreted from the hypothalamus and increases fetal

adrenocorticotropic hormone (ACTH) from the anterior pituitary, which stimulates fetal glucocorticoid (cortisol) production by the adrenal cortex. In response to these events, (1) placenta production of progesterone declines (removal of progesterone block) and estrogen increases; (2) production of estrogen increases uterine secretion of prostaglandin F2 (PGF2), myometrial receptors for oxytocin, and placental or ovarian secretion

of relaxin, which softens the cervix and relaxes pelvic ligaments to accommodate fetal expulsion; and (3) increased PGF2 production stimulates maternal release of oxytocin from the posterior pituitary, which further stimulates PGF2 production by the uterus and contractions of the myometrium with eventual delivery. (From Geisert RD: Learning reproduction in farm animals CD-ROM. Oklahoma State University, Stillwater.)

268 CHAPTER 35 leukocytes. Involution, first estrus, and first ovulation are delayed in cows with periparturient problems such as dystocia, twinning, uterine infections, ovarian cysts, injury, or metabolic diseases such as ketosis, displaced abomasum, and milk fever.13 Furthermore, all measures of reproductive efficiency are reduced in cows with periparturient

problems compared with normal cows. Infertility or reproductive failure often is difficult to resolve because of its multiple causes.

Postpartum Period Anestrus Initiating early reestablishment of normal estrous cycles after calving is essential to allow adequate time for cows to be inseminated and maintain a 12- to 13-month calving interval. Numerous studies in dairy cows, based

on observed estrous activity, ovulations, and resulting estrous cycles documented by repeated samples of milk or blood progesterone, indicated that nearly 95% resume cyclic ovarian activity by approximately 4 weeks after calving.13 Recent studies have indicated that in wellmanaged dairy herds, the proportion of cows not cycling by the end of the volunteer waiting period (i.e., 60 days post partum) is approximately 20% to 25%.

Milking Approximately 50% of dairy cows in one study14 expressed estrus before this first ovulation (according to daily video recordings during the first 80 days after calving), whereas the herdsman observed estrous behavior in only 20%. Second ovulations (at about day 44 post partum) were preceded by estrous behavior in 95% of the

dairy cows, whereas the herdsman observed such behavior in only 44%. By the third ovulation (at about day 64 post partum), 100% of the dairy cows were detected in estrus by video recordings, whereas the herdsman detected only 64%. Suckling In the beef cow, suckling prolongs anestrus, but its duration is shortened if calves are weaned at birth or suckling is limited.13 Suckled beef cows that calve in the spring

may not begin estrous cycles for 40 to 60 days. Early weaning of calves, however, usually initiates estrous cycles in most situations, regardless of body condition or nutritional status. Suckling per se (suckling and concurrent milk removal) is not essential to prolong anestrus, because cows maintained with their calves that were fitted with nose plates or muzzles so that they could

not suckle had periods of anestrus equal to cows maintained with their normally suckling calves. An intact udder is not essential, so long as the calf is maintained with its dam and attempts to suckle after bottle feeding.13 Suckling-induced hormones, such as prolactin, cortisol, and oxytocin, are increased in mastectomized cows when their own calves attempted to suckle, analogous

to those of udder-intact cows at the time of suckling by their own calves. In either case, concentrations of LH are low and pulses of LH are inhibited by suckling or attempted suckling events, so that anestrus is maintained.13 Partitioning of Available Nutrients and Body Condition Combined effects of various metabolic changes and nutrient repartitioning, essential for lactogenesis and galactopoiesis

in cattle, compete for nutrients that are essential to reinitiate estrous cycles after parturition. Nutrient intake, adequate availability of nutrients, diet composition, acute changes in body weight or body condition before or after calving, variously related metabolites, metabolic hormones, and overall energy balance are factors that correlate with the reestablishment of estrous

cycles and may be indicators of intervals to first postpartum ovulation. Metabolic functions are regulated in mammals to achieve two major purposes: self-survival and perpetuation of their species. Homeostatic mechanisms achieve the first purpose because they regulate the internal biochemical environment. Homeorhetic regulations achieve

the second purpose by altering metabolic support to sustain growth, pregnancy, or lactation. The concept of homeorhesis accounts for how various hormonal mechanisms orchestrate coordinated changes in metabolic pathways in specific body tissues necessary to support an existing physiologic function such as lactation or pregnancy at the expense of other, less vital bodily functions.

For example, when lactation begins, various priorities for nutrient utilization to support lactation are established. These priorities involve redirecting homeorhetic mechanisms that may be mediated by prolactin, somatotropin, insulin, insulin-like growth factor I (IGF-I), estradiol-17, glucocorticoids, and other hormones. The approximate ranking priority for use of available

energy in ruminants is as follows: (1) basal metabolism; (2) activity; (3) growth; (4) energy reserves; (5) pregnancy; (6) lactation; (7) additional energy reserves; (8) estrous cycles and initiation of pregnancy; and (9) excess reserves.13 In accordance with this prioritized use of available dietary nutrients, reinitiation of the estrous cycle and all of its associated components (i.e., gonadotropin

secretion, ovarian follicular development, and ovulation) occurs only after greaterpriority needs are met (i.e., maintenance, growth, lactation, and minimal energy reserves). Nutrient repartitioning for milk production and reproduction is the result of complex interactions among diet quantity and quality, nutrient reserves (body condition), and the demand for growth and metabolism.

Differences in management of milked and suckled cattle of various genotypes account for some of the differences in postpartum reproductive recrudescence, but as previously discussed, their lactational management is the major determinant. In general, if adequately fed, cows nursing a calf rarely experience a significant negative energy balance or extensive loss in body weight that

occurs in full-fed, milked cows producing up to five times more milk. The effect of nutrition in suckled cows depends somewhat on whether nutrition is adequate before or after parturition. In general, prepartum nutrient status, as estimated by body condition at parturition, is more important than that after calving. The relationship between body condition at calving and the interval to

first postpartum estrus in suckled beef cows is nonlinear. That is, the effects of poor body condition are greatest at Clinical Reproductive Physiology of the Cow 269 very low body condition scores (<4 on a 10-point body condition scoring system) and become less significant as body condition increases to a value of 7 or greater. When

nutrition is adequate in suckled cows, milk yield has little effect on postpartum anestrus, but when nutrition is limiting, particularly for cows having genotypes for high milk production, increased milk yield delays first ovulation and estrus. In milked cows, such a relationship of interval to first estrus and body condition has not been established. The magnitude of nutrient deficit (negative

energy balance), however, seems to be an important factor that inhibits first ovulation and has some relationship to the number of days to first ovulation. Postpartum changes in energy balance generally are predictive of when first ovulation will occur in milked cows. In milked cows, the nadir of energy balance occurs during the first or second week after calving and recovers

at a variable rate, with first ovulation occurring approximately 10 to 15 days after the nadir. Days to first ovulation are correlated positively (r = 0.76) with days to nadir of energy balance. Furthermore, because milk fat percentage is high near the nadir of energy balance, it may be a good indicator of the severity of nutrient deficit. During the enormous metabolic demands of high milk

production in early lactation, major amounts of nutrients are required for mammary synthesis of lactose, proteins, and triglycerides in the mammary gland that cannot be met by dietary intake. Nevertheless, milked cows with greater dry matter intake, despite having a negative energy balance, produce more milk, lose less body weight,

and ovulate earlier post partum than those with lower intakes. Cows with greater intakes also reach the nadir of energy balance earlier and experience a more severe, but shorter, period of negative energy balance, suggesting that when cows are more efficient in partitioning dietary and stored nutrients toward milk synthesis, they also are better able to recover ovarian cyclicity.

Hormonal and Follicular Changes Blood FSH concentrations increase from prepartum concentrations in suckled and milked cows within 5 days and peak before the appearance of each follicular wave after calving. The first or second dominant follicle generally ovulates in milk dairy cows after LH pulse frequency increases. Concentrations of LH in plasma or serum increase gradually from low, nearly nondetectable levels

at calving until about day 10, when some dairy cows are observed to begin pulsatile secretion of LH.1,13 The frequency of the LH pulses (determined by the pulse frequency of GnRH) increases over a period of days (to about one pulse per hour) until ovulation occurs. An hourly pulse frequency may be necessary for initiation of sufficient LH release, so that final follicular growth can occur

before first ovulation. An increase in IGF-I is coincident with increases in LH pulse frequency and earlier first postpartum ovulation. After ovulation, the frequency of GnRH and LH pulses decreases to one every 4 to 6 hours. Onset of these episodic patterns is delayed in suckled cows, particularly in those intensively suckled by several calves or suckled by one calf, but in poor body condition or in negative

energy balance.13 As a result, many follicular waves occur, each with its dominant follicle, but without ovulation until LH pulse frequency increases sufficiently. Studies have demonstrated that pulses of GnRH every 1 to 2 hours, and hence small pulses of resulting LH, will induce estrous cycles in suckled and milked cows.13 Part of this mechanism whereby LH pulses induce ovulation is

related to the ability of the hypothalamic-pituitary axis to respond to estradiol that is elaborated from developing antral follicles. In the early postpartum period, milked cows respond earlier than suckled cows to this positive feedback effect of estradiol on LH secretion.1,13 Not only does a temporal delay occur in the LH response to exogenous estradiol, but the magnitude of LH release in response to the same dose of estradiol increases as the

postpartum period progresses. Most current evidence suggests that the temporary inhibition of estrous cycles during the postpartum period is due to a block at the hypothalamic-pituitary level. Factors that influence the release of GnRH seem to be mediated within the brain or central nervous system by other hormones or endogenous opioid peptides.13 The latter belongs to a family of endogenous hormones that

mimic actions of the opiates, such as morphine or opium. Infusions of either of the opioid receptor antagonists naloxone and naltrexone increase concentrations of LH in milked and suckled cows, suggesting that endogenous opioid peptides limit LH secretion during the early postpartum period, when endogenous pulse frequencies of GnRH and LH are infrequent. The pulse frequency of LH increases gradually until a

preovulatory LH surge occurs to ovulate a mature graafian follicle. The first preovulatory surge of gonadotropins is followed, as expected, by a rise in progesterone in 3 to 4 days. In approximately 20% to 50% of dairy cows, however, this luteal phase is of short duration (<10 days), whereas in suckled cows weaned at about 30 to 40 days post partum or after their first ovulation, 90% will display

a shortened estrous cycle (<12 days). This short cycle appears to be due to a premature release of uterine PGF2, increased sensitivity of the luteal tissue to early luteolysis, and a higher concentration of uterine oxytocin receptors.1 Other Factors Exposing cows suckled post partum to bulls decreases the period of anestrus. Season influences the length of

anestrus in suckled cows. Although season may be modified by other factors such as suckling, nutrition, and genotype, truly seasonal effects are related to day length. Some evidence indicates that fall-calving primiparous (not multiparous) cows may have delayed intervals to first ovulation and estrus, unless supplemental lighting is given to provide 16 to 18 hours of total light per day.2

The relationship of day length and prolactin suggested that the high concentrations of prolactin associated with milking and suckling may inhibit the onset of ovarian cycles. Evidence against this mechanism, however, includes the following findings: (1) Treatment with pharmacologic agents to reduce prolactin concentrations does not hasten the onset of ovarian cycles; (2)

infusion of prolactin into cows fails to alter prolactin concentrations; and (3) concentrations of prolactin have 270 CHAPTER 36 not been shown to be higher in suckled than in milked cows.

References

1. Garverick HA, Smith MF: Female reproductive physiology and endocrinology of cattle. Vet Clin North Am Food Anim Pract 1993;9:223.

2. Hansen PJ: Seasonal modulation of puberty and the postpartum anestrus in cattle: A review. Livestock Prod Sci 1985; 12:309. 3. Patterson DJ, Perry RC, Kiracofe GH, et al: Management considerations in heifer development and puberty. J Anim Sci 1992;70:4018. 4. Day ML, Anderson LH: Current concepts on the control of puberty of cattle. J Anim Sci 1998;76:1 Suppl 3.

5. Hansel W, Convey EM: Physiology of the estrous cycle. J Anim Sci 1983;57:404 Suppl 2. 6. Fortune JE: Ovarian follicular growth and development in mammals. Biol Reprod 1994;50:225. 7. Espey LL: Current status of the hypothesis that mammalian ovulation is comparable to an inflammatory reaction. Biol Reprod 1994;50:233.

8. Niswender GD, Juengel JL, Silva PJ, et al: Mechanisms controlling the function and life span of the corpus luteum. Physiol Rev 2000;80:1. 9. Lucy ML, Savio JD, Badinga L, et al: Factors that affect ovarian follicular dynamics in cattle. J Anim Sci 1992;70: 3615. 10. Thatcher WW, Meyer MD, Danet-Desnoyers G: Maternal recognition of pregnancy. J Reprod Fertil Suppl 1995;49:15. 11. Wood CE: Control of parturition in ruminants. J Reprod Fertil

Suppl 1999;54:115. 12. Kiracofe GH: Uterine involution: Its role in regulating postpartum intervals. J Anim Sci 1980;51:16 Suppl 2. 13. Stevenson JS, Lamb GC, Hoffman DP et al: Interrelationships of lactation and postpartum anovulation in suckled and