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03 September 2016

Lecture #12: THE GONADS: FEMALE REPRODUCTIVE ORGAN

THE FEMALE REPRODUCTIVE ORGAN

Function of the female reproductive system

1.      The function of the female reproductive system is to produce offspring and
thereby ensure continuity of the genetic code.
 2.          It produces eggs or female gametes, which each may unite with a male
gamete to form the first cell of any offspring.

3.          It also can provide nutrition and protection to the offspring for up to
several years after conception.

Structural plan of the female reproductive system

1.      Essential organs – gonads are the paired ovaries; gametes are ova produced
by the ovaries – the ovaries are also internal genitals.

2.      Accessory organs

a.      Internal genitals – uterine tubes, uterus and vagina – ducts or duct
structures that extend from the ovaries to the exterior

b.      External  genitals – the vulva

The Uterus
1.      Structure of the uterus

a.      Size and shape of the uterus

(1)   The uterus is pear–shaped and has two main parts – the cervix and the
body.

b.      The wall of the uterus is composed of three layers

(1)   The inner endometrium

(2)   Middle myometrium
(3)   Outer incomplete layer of parietal peritoneum
 c.       Cavities of the uterus – the cavities are small because of the thickness of
the uterine walls

(1)   The body cavity’s apex constitutes the internal os and opens into the
cervical canal, which is constricted at its lower end and forms the
external os that opens into the vagina.

d.     The blood to the uterus is supplied by uterine arteries

2.      Location of the uterus

a.          The uterus is located in the pelvic cavity between the urinary bladder
and the rectum.

b.      The position of the uterus is altered by age, pregnancy and distension of
related pelvic viscera

c.            The uterus descends, between birth and puberty, from the lower
abdomen to the true pelvis.

d.     The uterus begins to decrease in size at menopause.

3.      Function of the uterus

a.      The uterus is part of the reproductive tract and permits sperm to ascend
toward the uterine tubes.

b.      If conception occurs, the offspring develops in the uterus

(1)    The embryo is supplied with nutrients by endometrial glands until

production of the placenta

(2)    The placenta is an organ that permits the exchange of materials

between the mother’s blood and the fetal blood but keeps the two
circulations separate.

(3)    Myometrial contractions occur during labor and help push the
offspring out of the mother’s body.

c.            If conception does not occur, outer layers of endometrium are shed
during menstruation
 (1)   Menstruation is a cyclical event that allows the endometrium to renew
itself.

The Uterine tubes

1.      Uterine tubes are also called Fallopian tubes or oviducts

2.          Uterine tubes are attached to the uterus at its upper outer angles and
extend upward and outward toward the sides of the pelvis

3.      Structure of the uterine tubes

a.      Uterine tubes consist of mucous, smooth muscle and serous lining

b.          Mucosal lining is directly continuous with the peritoneum lining the
pelvic cavity

(1)   Tubal mucosa is continuous with that of the vagina and uterus, which
means it, may become infected with organisms introduced into the
vagina.

c.       Each uterine tube has three divisions

(1)   Isthmus
(2)   Ampulla
(3)   Infundibulum

4.      Function of the uterine tubes

a.          Uterine tubes serve as transport channels for ova and as the site of
fertilization

The Ovaries
1.      Location of the ovaries

a.          The ovaries are nodular glands located on each of side of the uterus,
below and behind the uterine tubes.

b.      Ectopic pregnancy – development of the fetus in a place other than the
uterus.
 2.      Microscopic structure of the ovaries

a.      The surface of the ovaries is covered by the germinal epithelium

b.      Ovarian follicles contain the developing female sex cells.
c.       Ovum – an oocyte released from the ovary

3.      Functions of the ovaries

a.      Ovaries produce ova – the female gametes

b.      Oogenesis – process that results in formation of a mature egg
c.       The ovaries are endocrine organs that secrete the female sex hormones
(estrogens and progesterone)

The Vagina
1.          The vagina is a tubular organ located between the rectum, urethra and
bladder.

2.      Structure of the vagina

a.          The vagina is a collapsible tube capable of distension, composed of

smooth muscle, and lined with mucous membrane arranged in rugae.

b.      The anterior wall is shorter than the posterior wall because the cervix
protrudes into its uppermost portion.

c.       Hymen – a mucous membrane that typically forms a border around the
vagina in young pre–menstrual girls.

3.      Functions of the vagina

a.      The lining of the vagina stimulates the penis during sexual intercourse
and acts as receptacle for semen.

b.      The vagina is the lower portion of the birth canal.

c.       The vagina is a transport for tissue shed during menstruation

The Vulva
1.      The vulva consists of the female external genitals; mons pubis, labia majora,
labia minora, clistoris, urinary meatus, vaginal orifice and greater vestibular
 glands.

2.      Functions of the vulva

a.      The mons pubis and labia protects the clitoris and vestibule.

b.          Vestibular glands produce lubrication to reduce friction during

intercourse.

c.            The clitoris contains sensory receptors that send information to the
sexual response is of the brain.

d.        The vaginal orifice is the boundary between the internal and external
genitals.

The Perineum
1.      The perineum is the skin–covered region between the vaginal orifice and
the rectum.

2.      This area may be torn during childbirth

Regulation of secretion of ovarian hormone

1.      Ovarian cycle – ovaries from birth contains oocytes in primary follicles in
which the meiotic process has been suspended. At the beginning of
menstruation each month, several of the oocytes resume meiosis. Meiosis will
stop again just before the cell is released during ovulation.

During the ovarian cycle, the uterus also undergoes cyclic changes (uterine
cycle). The endometrial layer responds to the changes of the ovarian
hormones and is the source of menstrual discharge if pregnancy does not
occur. If pregnancy does occur, the endometrium participates in the
formation of placenta.

2.      Endometrial cycle or menstrual cycle

a.          Menses – a periodic vaginal bleeding, resulting from shielding of the

endometrial lining of the uterus.

b.      Post–menstrual phase

 (1)    An early follicle called the primordial follicle is observed in the
peripheral area in the ovarian cortex. It is composed of a primary oocyte
that is surrounded by a single layer of follicular cells. Several primordial
follicles differentiate into primary follicle.

(2)   The layer of follicular cells proliferates and forms a layer of granulosa
cells that surrounds the primary oocyte.

(3)   Connective tissue surrounding the follicle then differentiates to form

thecal cells.

(4)   The follicle becomes enlarged because the granulosa cell secrete a fluid
that not only fills spaces between cells but also displaces the oocyte to
one side, thus producing a large cavity in the center of the follicle. This
follicle is known as secondary follicle.

(5)   The follicle further matures to become a Graafian follicle, and although
several follicles begin this process, only follicle reaches the final stage.
The rest degenerates.

(6)   The Graafian follicles produce a bulge in the outer surface of the ovary.
The time required for the development of this mature follicle is
approximately 14 days and this period is known as the follicular phase
of the menstrual cycle.

c.       Ovulation – Graafian follicles ruptures and the ovum is expelled from it.

d.     Pre–menstrual phase

The Graafian follicle remaining in the ovary undergoes change and become
known as a corpus luteum (yellow body). The thecal and granulosa cells
undergo changes and secrete progesterone.

3.      Myometrial phase

If fertilization of the ovum does not occur, the corpus luteum ceases to secrete
hormones and becomes non–functional and is known as the corpus albicans
(white body). The time required for this process is about 14 days after
ovulation and is known as the luteal phase of the menstrual cycle.

4.      Gonadotropic cycle

 a.          The hypothalamus releases Gn–RH, which maybe controlled by
dopamine (inhibitors) and norepinephrine (stimulator). The gonadotrope
cells of the anterior pituitary release FSH, which in turn causes the
proliferation of the granulosa cells in the ovary. FSH, therefore, is
responsible for the early growth of the primary follicle. It may also
influence the conversion of testosterone to estradiol, which takes place in
the thecal cells. This estradiol that is produced causes the granulosa cells to
form more FSH receptors, making them more sensitive to FSH. The rising
levels of estradiol that occur in the early to mid–follicular phase inhibit the
production of pituitary FSH. However, in the late follicular phase, rising
levels of estradiol cause the pituitary to release LH. This surge of LH causes
ovulation.

b.          The release of Gn–RH from the hypothalamus also causes the anterior
pituitary to release LH. LH acts on the thecal cells of the ovary to induce
the synthesis of androgens and ultimately estradiol. The estrogen produced
diffuses into the granulosa cells. LH is necessary for the final follicular
growth and ovulation and works synergistically with FSH. It influences the
change of the granulosa cells into lutein cells and thus the production of
progesterone. It has been postulated that progesterone may serve in the
negative feedback mechanism for the LH release from the anterior
pituitary.

The Cervical mucus

Cervical mucus is a complex secretion produced by the gland of the endocervix and
it has the following characteristics:

1.      It is composed of 92 – 98% water and approximately 1% inorganic salts, of

which NaCl is the main constituents

2.      The mucus also contains free simple sugars, polysaccharides, proteins and
glycoproteins.

3.      Its pH is usually alkaline and ranges from 6.5 to 9.0

4.      Spinnbarkeit – is the property that allows cervical mucus to be stretched or

drawn into a thread. Spinnbarkeit can be estimated by stretching a sample of
mucus between 2 glass slides and measuring the maximum length of the
thread before it breaks. At midcycle, spinnbarkeit usually extends 10cm.
 5.          Ferning or arborization refers to the characteristic microscopic pattern
cervical mucus forms when dried on a slide. Ferning results from the
crystallization of inorganic salts around small and optimal amount of organic
materials present in cervical mucus.

The Ovarian hormones

1.      Estrogens are synthesized by the thecal cells of the ovaries in female and
small amounts are produced by the adrenal cortex in male and female and by
the testes in male. The estrogen metabolites are

a.      Estradiol
b.      Estrone
c.       Estiol

2.          Progesterone is produced mainly by the granulosa (lutein) cells of the

corpus luteum in female. It is also produced by the placenta in pregnancy, and
small amount can be produced by the adrenal cortex. The main urinary
metabolite is pregnanediol.

3.      Dehydroepiandrosterone (DHEA) is an androgen primarily derived from

the adrenal gland. Its conjugation product DHEA–sulfate in plasma has
replaced the 17–ketosteroid.

4.      Relaxin is polypeptide that has been extracted from the ovary. In certain
animal species, it appears to play important at the time of parturition, causing
relaxation of the pelvic ligaments and softening of the uterine cervix. It is
found in ovary, blood and placenta. It also increases glycogen synthesis and
water uptake by the myometrium and decreases its contractility.

Laboratory evaluation of ovarian function

1.          Urine estrogens to monitor development of the unborn child during
pregnancy.

a.          Kober reaction involves heating a urine sample in a strong aqueous

sulfuric acid solution containing hydroquinone. After cooling and dilution,
the absorbance of the resulting reddish–brown color is measured and total
estrogen concentration determined.

b.      Assay interferences

 (1)   Falsely decreased: ampicillin, neomycin, hydrochlorothiazide

(2)   Falsely elevated: meprobamate, L–dopa, phenolphthalein

2.      Serum estradiol to monitor ovarian tumors. Decreased level may be found
in primary and secondary ovarian failure as well as in adrenal gland
malfunction.

Reference range:

a.      Female

Prepubertal                           4 – 12 pg/ml

Early follicular phase          30 – 100 pg/ml
Late follicular phase                        100 – 400 pg/ml
Luteal phase                         50 – 150 pg/ml
Post menopausal                 5 – 18 pg/ml

b.     Male

Prepubertal                           2 – 8 pg/ml
Adult                                      10 – 60 pg/ml

3.      Serum progesterone has been used primarily for the evaluation of fertility
in females, in particular for the detection of ovulation.

Reference range:

a.      Male                                 0.12 – 0.3 ng/ml

b.      Female    

Menstrual cycle

      Follicular phase       < 1 ng/ml

      Luteal phase             5 – 20 ng/ml

Pregnancy

      1st trimester               20 – 50 ng/ml

      2nd trimester              50 – 100 ng/ml
      3rd trimester               100 – 400 ng/ml
 4.      Serum DHEA – S is valuable for the assessment of adrenal cortical function.

Reference range:

a.      Adult males                    3.6 – 6.3 ng/ml (12.5 – 21.9 nmol/L)

b.      Females                           4.4 – 6.0 ng/ml (15.3 – 20.8 nmol/L)

Inhibitors of ovarian function

1.      Gn–RH – leuprolide, buserelin, nafarelin
2.      Tamoxifen
3.      Danazol
4.      Antiprogestins: Mifepristone, epostane
5.      Antiandrogens: Cyproterone, cyproterone acetate, ketoconazole

Clinical significance of Ovarian Function Test

1.      Female Infertility

a.          Uterine leimyonas, adenomas of smooth muscle cells, are the most
common tumors of the uterus. If present, they can interfere with the
implantation of a fertilized ovum

b.      Partial or total destruction of the endometrial lining of the uterus known
as Asherman’s syndrome, also makes implantation impossible.

c.       Tubal abnormalities usually result in decreased patency of the lumen of

the oviducts. This can be caused by chronic infections as well as
endometriosis.

d.     Ovarian abnormalities usually result in anovulation, which is the failure

to produce a mature ovum for fertilization. This condition may be caused
by infections, tumors or polycystic ovary disease (PCOD).

e.          At the pituitary level, hypersecretion of prolactin (PRL) due to an

adenoma may result in infertility. This condition is usually accompanied by
amenorrhea and galactorrhea. Hypersecretion of PRL may also be seen in
patients taking certain medications such as dopamine antagonists or in
some cases of hypothyroidism.
 f.        If the hypothalamus is not producing Gn–RH, ovulation will not occur.
Tumors of the hypothalamus are rare causes of disruption of Gn–RH. More
common causes include stress, weight loss, exercise and chronic illness.

2.      Hirsutism

Hirsutism in women is defined as excessive growth of hair in male

distribution. The face, chest, abdomen and sacral regions are commonly
affected. Hirsutism is associated with normal or moderately increased levels
of testosterone.

Virilizaton on the other hand, is an abnormal development of the secondary

male sex characteristics. These characteristics may include hirsutism but also
hoarse voice, acne, clitoral enlargement and changes in body mass
distribution. Virilization is caused by greatly increased levels of testosterone.

Causes of hirsutism

a.      Primary hyperandrogenemia

(1)    Congenital Adrenal Hyperplasia (CAH) is a genetic disorder

characterized by the deficiency or absence of enzymes involved in the
biosynthetic pathway for the production of cortisol. Since very little
cortisol is produced, the pituitary gland releases ACTH to compensate.
The adrenal gland is then stimulated and produces excessive amounts of
the steroid hormones above the enzymatic block. This usually results in
excessive androgen production.

(2)    Polycystic Ovary Disease (PCOD) linked to an abnormal release of

LH by the pituitary. The hypersecretion of LH causes thecal hyperplasia
in the ovary and thus increased androgen levels.

(3)    Tumors of the adrenal gland and ovary can produce massive
amounts of androgens.

b.      Secondary hyperandrogenemia

(1)   Pituitary adenomas, testicular feminization, hypothyroidism and Type

II Diabetes mellitus

(2)   Excessive secretion of ACTH, growth hormone and PRL from pituitary
 c.       Idiopathic hirsutism is a genetically determined increased sensitivity
of the hair follicle to androgens

3.      Amenorrhea

Amenorrhea is the absence of vaginal bleeding. Amenorrhea can be a

physiologic process, such as occurs with pregnancy, or it can be pathologic.
The pathologic causes of amenorrhea maybe either primary or secondary.

a.          Primary amenorrhea is defined as having no previous vaginal

bleeding. Among healthy females, 99% have begun to menstruate by the
age of 16. Signs of puberty, such as breast development and appearance of
pubic hair, develop before menarch. If a female reaches the age of 14
without showing any signs of puberty or having begun to menstruate, the
diagnosis of amenorrhea is made.

Causes of amenorrhea:

(1)    Chromosomal abnormalities like Turner’s syndrome (gonadal

dysgenesis)

(2)    Congenital structural malformation like Mullerian agenesis which is

the absence of uterus, fallopian tubes or vagina.

b.        Secondary amenorrhea is defined as the absence of menses for 6

months or for the equivalent three previous cycle intervals, whichever is
longer.

Causes of secondary amenorrhea:

(1)   Weight loss, strenuous exercise, drugs and stress

(2)   Asherman syndrome
(3)   Primary hypothyroidism