Female Reproductive Biology

Oleh : dr. Ahmad Fakhrozi Helmi

Pembimbing : dr. Etriyel Myh, Sp. U

Female Reproductive Biology

EMBRYONIC DEVELOPMENT
THE NEONATAL OVARY
PUBERTY
THE OVARIAN CYCLE
PREGNANCY
LABOR AND DELIVERY
MENOPAUSE

EMBRYONIC DEVELOPMENT
The Ovary
Genetic sex is determined at the time of
conception when a spermatozoa fuses with
the oocyte.
The fetal gonad thickening along the
urogenital ridge overlying the mesonephros
consisting of coelomic epithelial cells and
underlying mesenchyme.
The primordial germ cells begin development
in the yolk sac at 4 weeks' gestation
migrate and differential growth to urogenital
ridge

The numbers of cells

exponentially increasing by
mitosis, and meiosis where
they arrest in prophase of the
first meiotic division
The primordial germ cells
become surrounded by a
single layer of mesenchimnal
cells from the urogenital ridge
and form a primordial follicle.
At 16 weeks' gestational age,
the process of atresia begins
to affect germ cell

 The Uterus
The uterus two longitudinal infoldings of the
coelomic epithelium just lateral to the
mesonephros the mullerian ducts uterine
body.
The distal ends of the mullerian ducts remain
unfused to form the fallopian tubes

 The undifferentiated human embryo at 5 to

6 weeks' gestational age has both
mesonephric ducts and muellerian ducts.
the muellerian ducts continue
development into fallopian tubes, uterine
body, and the upper part of the vagina
the mesonephric ducts undergo
regression

 External Genitalia
The external genitalia of male and female
embryos is undifferentiated at 5 to 6 weeks,
depending on the hormonal milieu.
The female fetus androgen levels ,
1. The genital tubercle forming the clitoris;
2. The folds of the urogenital sinus forming the labia minora;
3. The urogenital sinus contributing to formation of the lower
vagina
4. the labioscrotal folds forming the labia
majora

THE NEONATAL OVARY

The total endowment of germ cells has been
reduced from 20 million to 1 to 2 million by birth.
This decrease in maternal steroids negative
feedback on the fetal pituitary gonadotrope
release of gonadotropins, follicle stimulating
hormone (FSH), and luteinizing hormone (LH)
Gonadotropin levels remain elevated for 12 to 24
months before reaching a nadir in early
childhood which lasts until puberty.

PUBERTY
Time of transition
from immaturity to a
sexually mature adult.
Puberty is heralded
by activation and
maturation of the
hypothalamic pituitary
gonadal axis, which
culminates in sexual
maturity.

 the reduction of negative feedback of estrogen on the

hlpothalamic pituitary axis gonadotropin and estrogen
levels onset of secondary sexual characteristics.
The development of estrogen-induced positive feedback
on the hypothalamic pituitary axis is a late manifestation
of puberty and correlates with ovulation.
Positive feedback the mature pituitary is exposed to
elevated levels of estrogen for a prolonged time. A surge
of gonadotropins occurs, known as the LH surge, and is
responsible for inducing ovulation.

 The onset of menses is usually followed by irregular

cycles for a few years consistent with oligo-ovulatory
cycles.
The menses do not become regular until maturation of
the positive feedback mechanism and onset of regular,
ovulatory cycles.
The onset of positive feedback in the hypothalamic
pituitary gonadal axis heralds the onset of regular,
ovulatory cycles with the resultant potential for
pregnancy

 Precocious Puberty
Defined as pubertal changes before the age
of 8 years and demands a thorough systemic
evaluation.
The causes of precocious puberty can be
divided into
GnRH dependent
GnRH independent

 The workup should focus on defining the

etiology and eliminating the possibility of
serious illness.
The initial evaluation Thorough history
and physical examination (detailed historic
evaluation of growth and the development
of secondary sexual characteristics)
Evidence of heterologous sexual development
A thorough neurologic, abdominal, and pelvic
examination

 Laboratory evaluation of patients should

include
serum gonadotropins and steroid levels
GnRH test

 Important radiologic tests include

Bone age
CT-Scan (Head, Adrenals)
Pelvic ultrasonography
MRI

 Pubertal Delay
Lack of sexual development may also be a
sign of serious illness.
signs of potentially serious pathology and
demand a rapid, thorough evaluation:
lack of onset of menses by age 14 with no signs of
secondary sexual characteristics.
Iack of menses by age 16 regardless of secondary
sexual characteristics
prolonged duration of puberty (>4.5 years)

 The initial evaluation

signs of past poor health
evidence of excess exercise or abnormal
eating habits
chronologic height and weight records.

The physical examination

height and weight measurements
Tanner staging.
detailed neurologic examination

 The laboratory evaluation

thyroid function tests, prolactin,
gonadotropins, steroid levels (both gonadal
and adrenal)

bone age and skull imaging

cytogenetic testing

 Treatment of subjects with delayed

puberty is determined by the etiology
Hormone replacement therapy to
stimulate development of secondary
sexual characteristics.

THE OVARIAN CYCLE

The ovary serves important roles in
production of gametes and ovarian
steroids.
The human menstrual cycle is divided into
follicular, luteal, menstrual
The menstrual cycle is a continuum of
follicular development, ovulation, and
luteinization

 The follicular phase is characterized by a

series of events involving feedback
mechanisms which allow for the
sequential development of a follicle,
usually resulting in the release of a single
ovum at ovulation.

 Ovulation with the release of a mature oocyte occurs

after the LH surge. Ovulation occurs 10 to 12 hours after
the LH peak and 34 to 36 hours after the start of the LH
surge.
Resumption of meiosis and stimulation of a number of
proteolytic enzymes, which digest the walls of the follicle,
allow the oocyte to release; this occurs after the
gonadotropin surge.

 After ovulation corpus luteum

granulosa cells continue to enlarge and
develop a vacuolated appearance
accumulates a yellow pigment known as lutein
A rapid period of vascularization with in
growth of capillaries into the granulosa cells

 The corpus luteum produces ovarian

steroids, primarily progesterone and
estrogen. The secretion of sex steroids is
episodic during the luteal phase and
correlates with the pulsatile release of LH.
estrogen and progesterone the
endometrium into an environment which
will accept and nurture the developing
embryo.

 A normal menstrual cycle luteal phase is

approximately 14 days (range is 11-17 days).
The corpus luteum is programmed to undergo
involution in 9 to 11 days after the LH surge
unless rescued by human chorionic
gonadotropin (hCG)
hCG maintains the corpus luteum until the ninth
to 10th week of gestation.

PREGNANCY
Pregnancy is a unique situation in terms of
steroidogenesis
Progesterone is synthesized from
cholesterol from any source
(i) conversion of acetate to cholesterol
(ii) hydrolysis of stored cholesterol esters
(iii) low density lipoprotein (LDL)-cholesterol

 During pregnancy, progesterone is

produced initially by the corpus luteum (by
HCG from the syncytiotrophoblast).
7 to 10 weeks, both the placenta and
corpus luteum are producing
progesterone.
After 10 weeks, the placenta is the primary
source of production.

 Progesterone plays a number of important

roles in pregnancy
preparation and maintenance of the uterine
endometrium
supplies the fetus with precursors for the
production of glucocorticoids and
mineralocorticoids.

 Estrogen concentrations are elevated during pregnancy.

Estrogen synthesis depends on the production of
adequate precursor steroids by the developing fetus.
Estrogens depend primarily on the 19-carbon steroid
precursors, androgens, for their production. In early
pregnancy come from the mother, whereas later from the
fetal adrenal.

 The thin outer

definitive zone of the
fetal adrenal 7
weeks' gestation.
Fetal adrenal
develops under the
control of HCG,
ACTH, prolactin.
DHEAS is the primary
19-carbon precursor
secreted by the fetus

 The major protein

hormones of pregnancy
are produced by the
placenta.
The placenta releases a
number of hormones
similar to those produced
by the hipothalamus and
pituitary

 HCG is a glycoprotein hormone produced by the

syncytiotrophoblast of the placenta.
The concentration of HCG is 10 mIU/mL, double
every 2 to 3 days during the first weeks of a
normal gestation.(10 weeks' gestation
100,000 mIU/mL).
HCG plays a vital role
rescuing the corpus luteum from demise.
stimulation of the fetal testes to produce androgen
and stimulation of the fetal adrenal gland.

 Human placental lactogen (HPL) is also

secreted by the cyncytiotrophoblast and is
composed of a single polypeptide chain
with two disulfide bonds.
HPL functions by inducing insulin
resistance (carbohydrate intolerance)
along with increasing insulin-like growth
factor (IGF-I) levels.

 HPL maintains glucose levels for the

developing fetus.
glucose levels , free fatty acids are stored
as triglycerides.
glucose levels , HPL levels , resulting
mobilization of free fatty acids in the mother.

 -Fetoprotein is produced primarily by the

fetal liver and has no known fetal function.
-Fetoprotein is a glycoprotein that
resembles albumin and reaches high
levels in the fetal circulation.

 Prolactin secreted into

(i) the fetal blood stream
(ii) amniotic fluid
(iii) maternal blood stream.

Prolactin secreted from the respective

pituitary glands,maintains its regulatory
pathways, primarily under negative control
by dopamine.
Prolactin is also synthesized by decidua

 A number of polypeptide hormones are

produced by the placenta,
human chorionic growth hormone,
human chorionic thyrotropin,
human chorionic adrenocorticotropin.

LABOR AND DELIVERY

Labor occurs contractions sufficiently
coordinated cervical effacement and
dilatation.
Initiation of labor involves communication
between the fetal membranes and uterine
decidua.
Labor is characteized
oxytocin receptors in the myometrium,
increase in myometrial gap junctions,
cervical effacement and dilatation.

 Labor can be divided

(i) Stage I, which involves effacement and
dilatation of the cervix
(ii) Stage 2, which involves propulsion of the
fetus through the bony pelvis
(iii) Stage 3, which starts after delivery of the
fetus and ends with delivery of the placenta.
Some authors describe a fourth stage

MENOPAUSE
Menopause is a retrospective diagnosis
marked by the cessation of menses for 12
months due to follicular exhaustion.
Waning ovarian function and culminating
in hipogonadism.

 Vasomotor Symptoms
The hot flush a hot, flushing feeling in the face,
head, neck, and upper chest with a typical duration of
1 to 5 minute
Core temperature peripheral vasodilatation
blood flow to the skin, a rise in temperature, and
sweating.
The loss of estrogen production has an important role
Estrogen replacement therapy is the most efficacious
therapy

 Urogenital Atrophy
Loss of estrogen can also result in urogenital
atrophy.
Recurrent vaginitis, painful intercourse,
pruritus, vaginal stenosis, dysuria, recurrent
urinary tract infections, urinary incontinence.
The treatment for urogenital atrophy is the
local delivery of estrogen or the use of
lubricants.

 Bone Loss
Estrogen loss at menopause results in an accelerated
osteoclast mediated breakdown of bone without an
increase in calcium deposition.
The prevention and treatment including dietary
intervention by increasing calcium, adequate vitamin
D, weight bearing exercise, discontinuing smoking
and excess caffeine.
pharmacologic Estrogen replacement,
bisphosphonates and calcitonin.

 Cardiovascular System
There are a number of cardiovascular risk
factors that increase with advancing age and
the hipogonadal state of the menopausal
woman.

 Hormone Therapy
Individualized with the lowest dose of
estrogen used for the shortest duration to
control menopausal symptoms.
This treatment should only be initiated after a
thorough discussion of risks and benefits'

Thank You