Sc21L03 Physiology of Ovarian &

Menstrual Cycle
Ovarian Function
Hormone Production female phenotype
(oestrogen dominates)
Oocyte Release menstruation + reproduction
Process of Oogenesis
Max no. of eggs present before birth 7
million eggs
At birth 2 million egg; First Period 0.5
million eggs
Gradual LOSS of eggs as women age
Menopause essentially no eggs
The Ovarian Cycle THREE phases
Figure 1 Development of Ovarian Follicle oocyte released it
1. Follicular Phase: Days 1-10
is around 14-18mm (ovulation)
Hormones -> 10-20 follicle to grow in
ovaries
Oestrogen matures ONE oocyte
Uterine lining renews
2. Ovulatory Phase: Days 11-14

Cell division of oocyte

Follicle wall thins + ruptures oocyye

released

Oocyte enters abdominal cavity near

fimbrae of fallopian tube

Uterine lining thickens

3. Luteal Phase: Days 14-28

oestrogen

egg travels to fallopian tubes uterus

remaining cells of follicle develop into

corpus luteum

lining continues to thicken

The Menstrual Cycle
Menstrual Phase (D1-5)
Functional layer of endometrium becomes detached
from uterine wall
Bleeding (menses)
Proliferative Phase (D6-14)
GnRH FSH+LH Follicular Development Oestrogen
Endometrium proliferates + thickens
Tubular glands + spiral arteries form
Stimulation of progesterone receptor
synthesis in endometrial cells
Late Proliferative Phase (Ovulation D13-14)
Glands long due to active growth
Stroma gradually become oedematous
Secretory Phase (D15-22)
Rising levels of progesterone (from corpus
luteum)
Enlargement of glands secrete mucus +
glycogen (prep for implantation of ovum)
Increased fluid in stroma
Late Secretory (D23-28)
Fertilisation does NOT occur corpus luteum degens.
Progesterone endometrium degenerates
Spiral arteries contract stroma capillary beds seep blood into endometrium menses
Cycle starts again with first day of menstrual flow

Regulation of Hypothalamic-Pituitary-Ovarian Axis

Steroid Feedback
At hypothalamus: (-) GnRH release
At pituitary: sensitise/desensitise to GnRH by
changing receptor nos
E2 LOW: negative feedback
E2 HIGH: positive feedback
Progesterone: negative feedback
Gonadal Dysfunction problem with:
Hypothalamus
Pituitary
Functional units (follicles)
Receiver (absent, insensitive, obstructed)
Ovarian Reserve (OR) no. and quality of follicles left in ovary at
given time
Antral follicular count (AFC) correlates well with ovarian
response, done early follicular phase
Usually each follicule: 2-10mm
Age-related Ovulation Dysfunction declining fertility with age
Germ cells in female NOT replenished during life
Attrition + utilisation of follicles decline in no. of oocytes from
birth to menopause
Quality of existing ooctyes with age remaining follicles less
capable of fertilisation
Inhibin B production by small follicles DECREASED with age,
inhibin suppression of FSH secretion decreases, pituitary gland
secretion of FSH increases.
Elevated day-3 FSH in women with menses identify women with
depleted ovarian follicular pool
Summary
Ovaries embryologically separate from uterus
Ovaries: finite no. of eggs Max: in utero, Min: menopause
No. of oocyte can be small from outset or made so by insult to ovaries
Regular cycles: do NOT have ovulation problem
Women with reduced egg reserve can still ovulate normally
Ovaries need: FSH + LH in order to effecr ovulation
Without LH surge ovulation cannot occur spontaneously
Age related decline in fecundity = reduction in egg quantity + quality
Ultrasound scan measure of intactness/egg reserve
Polycystic Ovary Syndrome (PCOS) most common cause of anovulation
Pituitary gland adenoma secretes prolactin anovulation
FSH receptor malfunction ovarian dysfunction
X chromosome ovarian function
XY women have NO ovaries gonads are testes
Absent or fragile X chromosome are associated with impaired ovarian function
Combined oral contraceptive pills work by preventing ovulation

Sc21L05 - Histology of Male + Female Reproductive Systems

Organisation of:
Ovary female gametes (ova)
Small oval bodies
Attached to broad ligament of uterus by
mesovarium (short perioneal fold)
vessels leave + enter
Covered: germinal epithelium (E) +
Tunica Albiginea (TA) fibrous collagen
layer (merge with ovarian stroma)
Outer Cortex:
Follicles (F) 40m-1cm dia. in stoma
containing fibroblast-like cells
Inner Medulla:
RICH blood supply (very vascular)
Coiled helicine arteries (H) from mesovarium,
drained by large, tortuous, medullary vein
Endocrine function of ovary prod. hormones
Follicle Maturation
Primary Follicles: formed before Puberty some
Primordial Follicles spontaneously active
Flattened follicular cells become cuboidal
proliferate Zona Granulosa (stratified
epithelium)
1 oocyte ~ surrounded by Zona Pelucida
(ZP) prominent glycoproteins coat
Theca Folliculi (TF) proliferation of stromal
fibroblast-like cells. Differentiates into TWO
zones:
a. Theca Interna (TI) highly
vascularised synthesise steroid hormone
b. Theca Externa (TE) sheath of fibroblast like cells
Oocyte MAX size = 120
Fluid filled cavity (antrum) forms zona granulosa secondary follicle (still containing 1 oocyte)
Further growth of
follicle requires FSH
Start of Monthly
FSH produced
to develop further
LH starts: Theca
osterogen by
levels of
secretion
Only most advanced
FSH rest undergo
Dominant follicles
Mid-cycle LH surge
2 oocyte (arrests @
Polar Body (thrown
OVULATION oocyte into
uterine tube
After Ovulation

Cycle
triggers 20 pre-antral follicles
Interna secretes androgens ->
granulosa cells
oestrogen suppress FSH
(dominant) follicles survive falling
atresia
1.5-2.5cm Graafian Follicle
1 oocyte complete meiosis I
metaphase of meiosis II) + 1st
away)
Follicle ruptures discharge 2
peritoneal cavity near entrance of

Follicle collapses
Granulosa cells re-organise forming Corpus Luteum; granulosa lutein cells (G)
Granulosa Lutein Cells (G) secrete progesterone under influence of LH
Theca Interna cells resume secretion of androgens oestrogen by granulosa cells
levels of Progesterone suppress LH secretion
levels of LH, corpus luteum degenerates 10-14 days after ovulation Corpus Alcicans (dominant
feature of human ovary)
No Oestrogen + Progesterone FSH + LH secretion from pituitary resumes another cycle begins
IF fertilisation occurs developing placenta provides substitute for LH (chorionic gonadotrophin) to
maintain the corpus luteum

Uterine tube
Ovulation egg released into peritoneal cavity +
picked up by infundibulum of uterine tube
Fertilisation occurs most commonly in Ampulla
Movement of egg to uterus gentle peristalsis by
ciliated epithelial lining
Highly convoluted mucosa
Inner: circular, Outer: Longitudinal, smooth
muscles (M)
Simple columnar epithelium ciliated +
secretory peg cells
Uterus
Endometrium glandular mucosa

Height varies with menstrual cycle

Stratum basalis (B) persists throughout

cycles (below s.fun.)

Stratum functionalis (F) grows back during cycle lost during menstruation
Myometrium thick smooth muscle wall
a. Proliferative after menstruation

Oestrogen production resumes

Rapid proliferation restore stratum functionalis

Endometrial glands (straight) more coiled

b. Early Secretory Phase - after ovulation progesterone
predominates

(-) proliferation

(+) glandular epithelial cells to start forming glycogenrich secretion basally located vacuoles
c. Late Secretory Phase
Glands appear more saw-tooth like filled with glycogen-rich
secretion
Stroma most vascular + fluid accumulates between stromal
cells
d. Menstruation
Follows degeneration of corpus luteum
Loss of progesterone spasmodic constriction of spiral arteries
supplying S. functionalis
Leads to Ischaemia degeneration + loss of S. functionalis

Cervix
Endocervical Canal (EC) abrupt transition:
Simple Columbar Epithelium (uterus) Stratified
Squamous Epithelium of vagina (V)
Transformation zone: site of cervical carcinoma
Screen for early neoplastic changes, cells from
transformation zone + stained by Papanicolaou
method (Pap test)

Organisation of:
Testis
Divided into 250 lobules incomplete septa
(originate from tunica albuginea (TA))
Each lobule: 1-4 Seminferous Tubules
Spermatozoa produced in seminiferous tubules
drain into Rete Testis (RT)
Then to Epididymis via 15-20 Ductuli Efferentes

Seminferous
Tubues
Rete Testis (RT)

Seminferous Tubules
Epididymis
Site of production of male gametes
Lined by complex, Stratified Germinal Epithelium
Spermatogenesis
Progenitor cells: Spermatogonia Type A (dark) (SA) basal layer of epithelium
multiply by MITOSIS. Give rise to:
Spermatogonia Type A (pale) limited no. of mitoses generate clone of
descendants, culminates as:
Spermatogonia Type B (more-dispersed chromatin
SB) complete mitosis + enter meiosis as Primary
Spermatocytes (S1)
Nuclear divisions complete, but cytoplasmic division is
NOT clones remain connected by cytoplasmic
bridges (syncytium) persist until final stages of
spermatogenesis
Primary Spermatocytes, after normal S phase, enter
prophase of 1st meiotic division crossing over occurs
leave basal later of epithelium (takes 3 weeks)
Complete 1st meiotic division- two daughter cells:
2ndary Spermatocytes rapidly enter second
meiotic division (only lasts few hours)
2ndary Spermatocytes complete 2nd meiotic division yield Haploid Spermatids (S3 + S4)
Spermiogenesis morphological maturation of spermatids to spematoza 6 weeks in man
Condensation of Nucleus
Formation of Acrosome

Formation of Flagellum
Shedding of Unwanted cytoplasm ingested by Sertoli Cells

Sertoli Cells (St)

Tall cells span entire thickness of germinal epithelium
Oval nucleus prominent nucleolus
Extensive, lateral processes - connected by junctional complexes
Tight junctions create basal + luminal compartment make
blood-testis barrier (BTB)

Basal compartment = spematogonia

Luminal compartment = 1 spermatocytes, spermatids

+ developing spermatozoa
Provide mechanical + nutrition support
Generate BTB protect spermatozoa from immune system
Ingest unwanted cytoplasm during spermiogenesis
Produce testicular fluid
Secrete androgen binding protein (ABP) concentrate
testosterone
Leidig (Interstitial) Cells (L)
Between seminiferous tubules
Produce testosterone in response to LH
Pale + Frothy
Epididymis (E)
Spermatozoa passively flushes from
seminiferous tubules by testicular fluid
Pass epididymis via Rete testis + Ductuli
efferentes
Highly convoluted - 4-6m long
Tall, pseudostratified epithelium with
Stereocilia (giant microvilli)
Reabsorbs 90% testicular fluid concentrates sperm (distal part)
Ensheathed by coat of smooth muscle (contracts @ prox. end to
propel sperm, thick distally depends on sympathetic
stimulation, contracts violently at ejaculation, propel sperm into
vas deferens)
Vas Deferens
Continuation of epididymis larger lumen
Pseudostratified epithelium with stereocilia
Thick smooth muscles coat, inner + outer longitudinal layer,
circular later in between
Contract powerfully during ejaculation response to
sympathetic stimuli, propel sperm from urethra
Prostate
Ejaculatory ducts union of vas deferens + ducts of seminal
vesicles enter urethra within prostate
Walnut sized - below bladder surrounding first part of urethra
Secretes thin, milky fluid citrate + hydrolystic enzymes 2530% volume of semen
Microstructure
Branched tubule-acinar glands embedded in
fibromuscular stoma
FOUR zones:
1. Transition zone (TZ) around prostatic urethra, 5%
2. Central zone (CZ) around ejaculatory ducts, 20%
3. Peripheral zone (PZ) 70%
4. Anterior fibromuscular stroma contains no
glandular tissue
Arranged in THREE concentric groups:

Innermost peripheral mucosal glands open directly into urethra

Submucosal glands larger group open into urethra

by small ducts

Main prostatic glands 30-50, occupy peripheral zone,

open into urethra via long ducts
Tubuloalveolar glands lined by columnar secretory cells
Epithelial lining complex papillary folds
Stroma abundant smooth muscles cells
With age, spherical bodies Corpora amylacea (CA)
accumulate multiple lamellae of condenses glycoprotein
progressively calcified

Benign Prostatic Hyperplasia

Most men >50 years old
Compresses urethra urinary problems
Usually occurs in Transition zone
Prostate Cancer
Most common cancer in men
Second most common cause of death from cancer
Risk increases very steeply with age
Primarily affects peripheral zone, can occur without compression
of urethra so sometimes no symptoms

Sc21L06 Control of Testicular Function

Hypothalamic-Pituitary axis
Testicular Function
1. Production of sperm
2. Secretion of androgens
Seminiferous Tubules
Spermatogonial stem cells: sperm (gamete)
production
Sertoli cells; support, nutrition, protection,
secretory/exceretory
Spermatogenesis
Starts at puberty under influence of GnRH

Spermatogen
esis

Spermiogenes
is: repackaging

Spermiogenes
is

Mature Sperm

Maintains species
Mitosis followed by Meiosis
120 mil. sperm/ day
Cycle: 72 days

Sertoli Cells
Provide structural support
Porivde nutrients for mature sperm
Eliminate degenerate germ cells - ;residual bodies
Secretes Inhibin, ABP, AMH + growth factors
Leidig Cells
Secrete androgens (C19) mainly testosterone
Actions of testosterone
Male hormone anabolic ( bone + muscles mass)
Primary + Secondary sexual characters
Libido + Sexual behaviour
Stimulates Sertoli cells +
spermatogenesis

Sperm Transport
1.

Ejaculation: deposition of sperm in vagina (acidic)

2. Cervix: mucous barrier + crypts act as sperm reservoirs
3. Uterus + Tubes: mild contraction to propel sperm towards egg
4. Ampullary portion of Tube: fertilisation

Sperm Capacitation
Switching on of sperm HYPERACTIVE
takes 4 hours after ejaculation
Cholesterol loss + Ca2+ influx (ATP production)
Acrosome Reaction
Triggered by contact with oocyte
Interaction with ZP3 protein on oocyte membrane
Leads to exposure of hyaluronidase + acrosin enzymes
Facilitates oocyte penetration
Oocyte Activation
Release of cortical granules clock polyspermic penetration
Resumes meiosis II
Formation of male + female pro-nuclei (fertilisation)
Factors affecting Sperm Production
Recreational anabolic abuse
Increase muscle + bone mass
Stops sperm production
Non-hormonal e.g. Vasectomy, disruption of BTB