TISSUE

BIOCHEMISTRY
(BCH 408)
THE FEMALE
REPRODUCTIVE
SYSTEM

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REPRODUCTIVE SYSTEM
Human reproduction is a complex and fascinating process .The male and female reproductive system functioning
together produce a new life.
FEMALE REPRODUCTIVE SYSTEM
External Genitalia:
1. Vulva
The female external reproductive organs consist of the mons pubic, which is covered with pubic hair; two folds of
tissue, called the labia majora and labia minora, which surround a space called vestibule.
Mons Pubis
The mons pubis is formed at the upper margin of the symphysis pubis and is shaped like an inverted triangle. It is
located over the two pubic bones of the pelvic. This structure is composed of fatty tissue lying beneath the skin and
from puberty on, is covered with varying amount of hair. The mons pubis surrounds delicate tissue and protects it from
injury.
Labia Majora and Labia Minora
The labia majora : are two folds of fatty tissue that form the lateral boundaries of the vulva. They are covered with
coarse skin and pubic hair on the outer aspect and are smooth and moist on the inner aspect , where the openings of
numerous small glands are found.
The labia minora :are soft folds of skin that are rich in sebaceous glands. The labia minora are moist and are
composed of erectile tissue containing loose connective tissue , blood vessels, and involuntary muscles. The functions
of the labia minora are to lubricant and waterproof the vulvar skin and to provide bactericidal secretion that help
prevent infections.
Clitoris
The clitoris is a small, sensitive structure that, like the penis, is composed of erectile tissue, nerves, and blood vessels;
it is covered at the tip with very sensitive tissue. It exists primarily for female sexual enjoyment.
Vaginal Vestibule
The vaginal vestibule is a boat shaped depression enclosed by the labia minora and is visible when the labia minora are
separated. The vestibule contains the vaginal opening ( introitus ) , which is located between the external and internal
genitalia. The vestibule contains the openings of five structures that drain into it the ureteral meatus, skene’s ducts, and
the ducts from Bartholin;s glands that are located on each side of the vagina. The vestibule ends with the formation of
the fourchette.
2. Urethra
The opening to the urethra is just below the clitoris. Although it is not related to sex or reproduction, it is included in
the vulva. The urethra is actually used for the passage of urine. The urethra is connected to the bladder. In females the
urethra is 1.5 inches long, compared to males whose urethra is 8 inches long.

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3. Hymen
The hymen is a thin, elastic, mucous membrane that partially covers the vagina in young females. Does not seem to
have a specific physiological function or purpose. Many shapes are possible. Normal variations of the hymen range
from thin and stretchy to thick and somewhat rigid; or it may also be completely absent.

4. Perineum
The perineum is the short stretch of skin starting at the bottom of the vulva and extending to the anus. It is a diamond
shaped area between the symphysis pubis and the coccyx. This area forms the floor of the pelvis and contains the
external sex organs and the anal opening. The perineum in some women may tear during the birth of an infant and this
is apparently natural. Some physicians may cut the perineum preemptively on the grounds that the "tearing" may be
more harmful than a precise cut by a scalpel. If a physician decides the cut is necessary, they will perform it. The cut is
called an episiotomy.

Internal Reproductive Organs

1. Vagina
The vagina is a curved tube leading from the uterus to the external opening at the vestibule. It lies between the urinary
bladder and the rectum. Because it meets at a right angle with the cervix, the interior wall is about 2.5cm(1inch)
shorter than posterior wall, which varies from 7-10cm (approximately 2.8 to 4 inches). It consist of muscle and
connective tissue and is lined with epithelial tissue, which contains folds called rugae. These folds allow the vagina to
stretch considerably during childbirth. The epithelial cells lining the vagina show cyclic changes related to estrogens,
progestins, and androgens. Doderlein’s bacilli, which are normally present in the vagina, act on glycogen from the
epithelial cells to produce lactic acid. This maintains the acidity of the vagina and is the reason that the vagina is
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resistant to most infection. A change in the PH of the vagina, which can be caused by frequent douching ,
antimicrobial therapy, or deodorant tampons, can increase the vagina’s susceptibility to invading pathogens.
Purposes of the Vagina
• Receives a males erect penis and semen during sexual intercourse.
• Pathway through a woman's body for the baby to take during childbirth.
• Provides the route for the menstrual blood (menses) from the uterus, to leave the body.
• May hold forms of birth control, such as a diaphragm or female condom.
2. Cervix
The cervix consist of a cervical canal with an internal opening near the uterine corpus called the internal os and an
opening in to the vagina called external os the mucosal lining of the cervix has four functions:
1. Providing lubrication for the vagina
2. Acting as bacteriostatic agent
3. Providing an alkaline environment to shelter the sperm from the acidic vagina
4. Producing a mucous plug in the cervical canal during pregnancy
3. Uterus
The uterus (womb) is a hollow, pear-shaped, muscular organ. It is approximately 2.5 cm (1 inch) thick, 5cm (2inch)
wide, and 7.5cm (3inch) long. During pregnancy, the uterus can stretch and enlarge considerably. the weight of the
non-pregnant uterus is approximately 75g ; it increase to approximately 907 g during pregnancy, the uterus increase in
vascularity , which allows sufficient blood supply for its growth , and can stretch and enlarge to a considerable size .
After pregnancy, it returns almost entirely to its former weight, size, and shape. The uterus lies between the bladder
and the rectum. It is supported by two important pairs of ligaments, the round and broad ligaments. The uterus divided
into three parts : fundus (upper portion), the corpus (body), the cervix. The uterus have three layers (perimetrium,
myometrium, endometrium).
The following three functions of the uterus:
1. Menstruation: the uterus sloughs off of the endometrium or lining of the uterus.
2. Pregnancy: the uterus supports the fetus and allows fetus to grow.
3. Labor and birth: the uterine muscle contract and the cervix dilates during labor to expel the fetus

4. Fallopian Tube
The fallopian tubes extend laterally from the uterus, one to each ovary. They are small, narrow and approximately
10cm (4inch) long. The tubes carry the ovum from the ovary to the uterus by the contraction of the cilia: hair like

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projections found in the lining of the tubes. Extending from the ends of the fallopian tubes are small, fingerlike
projection called fimbriae. Their movement sweeps the ovum in to the tube, after which the ovum travels to the uterus.
It takes approximately 5 days for the ovum to travel the 10cm from the ovary to the uterus. Fertilization of the ovum
with sperm normally takes place in the outer third of the fallopian tube.
The four functions of the fallopian tube:
1. A passageway in which sperm meet the ovum
2. A site of fertilization
3. A safe nourishing environment for the ovum or zygote (fertilized ovum)
4. A means of transport ting the ovum or zygotes to the corpus of the uterus
5. Ovaries
The ovaries in the female and the testes in the male are similar in embryologic origin. The ovaries are two small,
almond shaped organs located on each gland. Approximately 2 million ova are present at birth. Many ova degenerate
until puberty, when a few thousand remain. During the course of a women’s reproductive life, only about 400 ova
mature enough to be fertilized. During each menstrual cycle one follicle matures into what is called a graafin follicle,
which contains the ovum that is released each month during ovulation. Estrogen released by the ovary stimulates the
development of secondary sexual characteristics such as the breasts. Progesterone is responsible for preparing and
maintaining the lining of the uterus for implantation of the ovum.
The ovaries have two functions:
1. The development and maturation of and later expulsion of the ovum (ovulation )
2. The secretion of hormones (estrogen & progesterone )
Breasts
The breast is composed of glandular, ductal, connective, and adipose tissue. Embedded in the fibrous tissue are fat and
lobules which make up the mammary glands, accessories to reproduction in women, but rudimentary and functionless
in men. In men, little fat is present in the breast, and the glandular system normally does not develop. In women, the
breasts are the most prominent superficial structure on the anterior thoracic wall, and the amount of fat in the glandular
tissue determines the size of the breasts. A small part of the mammary gland often extends into the axilla, forming the
axillary tail of Spence.

The mammary glands are modified sweat glands and are composed of 15-20 lobules, each drained by a lactiferous
duct. Each lactiferous duct independently drains on the nipple and is preceded by a small dilated portion known as the

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lactiferous sinus. It is in the sinus that milk collects during nursing and is "let down" by the suckling action of the
infant the process is called lactation the nipple in the center of breasts is surrounding by pigmented areola, which
darkens during pregnancy . Each breast consists of 10-20 lobes each lobe divided in to 20-40 lobules each lobule
divided into 20-80 alveoli.
During pregnancy high level of estrogen and progesterone produced by the placenta inhibit milk secretion after the
expulsion of the placenta there is abruptchange in estrogen and progesterone levels. This allows a hormone called
prolactin to be released from the interior pituitary gland when the infant sucks. Prolactin stimulate produce the milk
infant sucking also stimulate releasing oxytocin hormone from the posterior pituitary gland that causes eject the milk
from the alveoli in to the ductal system. The size of breast depends on the amount of fatty tissue in the breast.

FEMALE REPRODUCTIVE SYSTEM HORMONES

The reproductive system of a female, unlike men, shows regular cyclic changes that teleologically may be regarded as
periodic preparation for pregnancy and fertilization. In primates and humans, the cycle is a menstrual cycle, and its
most conspicuous feature is the periodic vaginal bleeding that occurs with the shedding of uterine mucose
(menstruation). The length of the cycle is notoriously variable, but an average figure is 28 days from the start of one
menstrual period to the start of the next. By common usage, the days of the cycle are identified by number starting
with the first day of menstruation. It begins at puberty, ranging from the ages
of 10 to 16, and ends at menopause at an average age of 51.[1][2][3]
FUNCTIONS
Hormones are secreted in a negative and positive feedback manner to control the menstrual cycle. Hormone secretion
begins in the hypothalamus where gonadotropin-releasing hormone (GnRH) is secreted in an increased, pulsatile
fashion once puberty starts. GnRH is then transported to the anterior pituitary, where it activates its 7-transmembrane
G-protein receptor. This provides a signal to the anterior pituitary to secrete stimulating follicle hormone (FSH) and
luteinizing hormone (LH). FSH and LH provide input to the ovaries. Within the ovarian follicle, there are 2 cell types
responsible for hormone production, theca cells, and granulosa cells. LH stimulates theca cells to produce
progesterone and androstenedione by activating the enzyme, cholesterol desmolase. Once androstenedione is secreted,
the hormone diffuses to the nearby granulosa cells. Here, FSH stimulates the granulosa cells to convert
androstenedione to testosterone then 17-beta-estradiol by activating the enzyme, aromatase. As levels of 17-beta-
estradiol or progesterone increase based on the phases of the menstrual cycle, there is negative feedback back to the
anterior pituitary to lower the levels of FSH and LH being produced and subsequently, the levels of 17-beta-estradiol
and progesterone produced. An exception to this is during ovulation. In this case, once a critical amount of 17-beta-
estradiol is produced, it provides positive feedback to the anterior pituitary to produce increased amounts of FSH and
LH. This feedback system is represented in figure 1. Additionally, within the feedback system, the granulosa cells
produce inhibin and activin, which inhibit and stimulate FSH release from the anterior pituitary, respectively. This
feedback mechanism is controlled by upregulating, to increase hormone production, or downregulating to decrease
hormone production, the GnRH receptors on the anterior pituitary.[4][5][6]

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MECHANISM
Phase 1: The Follicular, or Proliferative Phase
The first phase of the menstrual cycle is the follicular or proliferative phase. It occurs from day one to day 14 of the
menstrual cycle, based on the average duration of 28 days. The variability in the length of the menstrual cycle occurs
due to variations in the length of the follicular phase. The main hormone during this phase is estrogen, specifically 17-
beta-estradiol. The increase in this hormone occurs by the upregulation of the FSH receptors within the follicle at the
beginning
of the cycle. However, as the follicular phase progresses to the end, the increased amounts of 17-beta-estradiol will
provide negative feedback to the anterior pituitary. The purpose of this phase is to grow the endometrial layer of the
uterus. 17-beta-estradiol achieves this by increasing the growth of the endometrial layer of the uterus, stimulating
increased amounts of stroma and glands, and increasing the depth of the arteries that supply the endometrium, the
spiral arteries.
Additionally, this phase is also essential to create an environment that is friendly and helpful to possible incoming
sperm. 17-beta-estradiol achieves this by creating channels within the cervix, allowing for sperm entry. [7] The
channels are made within the abundant, watery, and elasticity changes of the cervical mucous. During this phase, a
primordial follicle begins to mature into a
Graafian follicle. The surrounding follicles begin to degenerate, which is when the Graafian follicle becomes the
mature follicle. This sets up the follicle for ovulation, the next step.
Ovulation
Ovulation always occurs 14 days before menses; therefore, with an average 28-day cycle, ovulation occurs on day 14.
At the end of the proliferative phase, 17-beta-estradiol levels are at a high due to the follicle maturation and increased
production of the hormone. During this time only, 17-beta-estradiol provides positive feedback for FSH and LH
production. This occurs when
a critical level of 17-beta-estradiol is reached, at least 200 picograms per milliliter of plasma. The high levels of FSH
and LH present during this time is called the LH surge. As a result, the mature follicle breaks, and an oocyte is
released. The changes to the cervix as initiated during the follicular phase further increase, allowing for increased,
waterier cervical mucous to better accommodate the possible sperm—the levels of 17-beta-estradiol fall at the end of
ovulation.
Phase 2: The Luteal or Secretory Phase
The next phase of the menstrual cycle is the luteal or secretory phase. This phase always occurs from day 14 to day 28
of the cycle. Progesterone stimulated by LH is the dominant hormone during this phase to prepare the corpus luteum
and the endometrium for possible fertilized ovum implantation. As the luteal phase ends, progesterone will provide
negative feedback to the anterior pituitary to decrease FSH and LH levels and, subsequently, the 17-beta-estradiol and
progesterone levels. The corpus luteum is a structure formed in the ovary at the site of the mature follicle rupture to
produce 17-beta-estradiol and progesterone, which is predominant at the end of the phase due to the negative feedback
system. The endometrium prepares by increasing its vascular supply and stimulating more mucous secretions. This is
achieved by the progesterone stimulating the endometrium to slow down endometrial proliferation, decrease lining
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thickness, develop more complex glands, accumulate energy sources in the form of glycogen, and provide more
surface area within the spiral arteries.
Contrary to the cervical mucous changes seen during the proliferative phase and ovulation, progesterone decreases and
thickens the cervical mucous making it non-elastic since the fertilization period passed, and sperm entry is no longer a
priority. Additionally, progesterone increases the hypothalamic temperature, so body temperature increases during the
luteal phase. Near the end of the secretory phase, plasma levels of 17-beta-estradiol and progesterone are produced by
the corpus luteum. If pregnancy occurs, a fertilized ovum is implanted within the endometrium, and the corpus luteum
will persist and maintain the hormone levels. However, if no fertilized ovum is implanted, then the corpus luteum
regresses, and the serum levels of 17-beta-estradiol and progesterone decrease rapidly.
Normal Menstruation
When the hormone levels decrease, the endometrium layer, as it has been changed throughout the menstrual cycle, is
not able to be maintained. This is called menses, considered day 0 to day 5 of the next menstrual cycle. The duration
of menses is variable. Menstrual blood is chiefly arterial, with only 25% of the blood being venous blood. It contains
prostaglandins, tissue debris, and relatively large amounts of fibrinolysis from endometrial tissue. The fibrinolysis
lyses the clot so that menstrual blood does not contain clots typically unless the flow is heavy. The usual duration of
the menstrual flow is 3-5 days, but flows as shorts as 1 day and as long as 8 days can occur in a normal female. The
amount of blood loss can range from slight spotting to 80 mL and the average being 30 mL. Loss of more than 80 mL
of the blood is considered abnormal. Various factors can affect the amount of blood flow, including medications, the
thickness of the endometrium, blood disorders, and disorders of blood clotting, etc.

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PATHOPHYSIOLOGY
Anovulatory Cycles
In some cases, ovulation fails to occur during the menstrual cycle. Such cycles are called anovulatory cycles, and they
are common for the first 12-18 months after menarche (The occurrence of the first menstrual period) and again before
the onset of menopause. When ovulation does not occur, usually no corpus luteum is found, and the effect of
progesterone on the endometrium is absent.[8] Estrogen continues to cause the growth of the endometrium, however,
and the proliferative endometrium becomes thick enough to break down and begin to slough. The time it takes for the
bleeding to occur is fluctuating, but it generally occurs in less than 28 days from the previous menstrual period. The
flow is also inconsistent and ranges from scanty to relatively profuse. [9]

CLINICAL SIGNIFICANCE
A female has an average of 450 menses throughout her lifetime; therefore, it is important to understand the menstrual
cycle and its physiology because of the various complications, consequences, and distress that it may have for a female
patient. A female presenting with primary or secondary amenorrhea will need to undergo clinical testing to diagnose
the reason. Still, reasonable testing from the level of the ovaries to the hypothalamus cannot be performed unless a
clinician thoroughly understands the hormone feedback system. Additionally, there may be problems with her menses
themselves, such as premenstrual syndrome, dysmenorrhea, or menorrhagia. Without an understanding of the female
anatomy and menstrual cycle physiology, a clinician would be unable to obtain a complete history and physical to
allow understanding of the underlying cause. Infertility is a prominent issue in our society, and the menstrual cycle is
the basis for how a woman’s body prepares for pregnancy, so each patient’s menstrual cycle must be evaluated as a
possible area of concern for her infertility. As clinicians, we must understand the menstrual cycle in its entirety to
provide relevant clinical care to our female patients. [10][11][12]

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estrogen-macrophage interplay in the homeostasis of the female reproductive tract. Hum
Reprod Update. 2018 Nov 01;24(6):652-672. [PubMed]
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GnRH secretion. Front Neuroendocrinol. 2020 Apr;57:100837. [PubMed]
8. Thomas VG. The Link Between Human Menstruation and Placental Delivery: A Novel
Evolutionary Interpretation: Menstruation and fetal placental detachment share common evolved
physiological processes dependent on progesterone withdrawal. Bioessays. 2019
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Pediatr Adolesc Gynecol. 2019 Jun;32(3):249-253. [PMC free article]
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11. Gunn HM, Tsai MC, McRae A, Steinbeck KS. Menstrual Patterns in the First Gynecological
Year: A Systematic Review. J Pediatr Adolesc Gynecol. 2018 Dec;31(6):557-565.e6.
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