Anatomy and Physiology of the Female Reproductive System

Anatomy of the Female Reproductive System

• Female reproductive organs include:
  • Ovaries
  • Uterine tubes
  • Uterus
  • Vagina
  • External genital organs
  • Mammary glands

Ovaries

• Broad ligament: Extension of the peritoneum that supports the uterus, uterine tubes, and ovaries.
• Ligaments of the ovaries:
  • Mesovarium: Peritoneal fold attaching the ovary to the posterior surface of the broad ligament.
  • Suspensory ligament: Extends from the mesovarium to the body wall. Contains ovarian arteries, veins, and nerves.
  • Ovarian ligament: Extends from the ovary to the superior margin of the uterus. Ovarian arteries, veins, and nerves enter the ovary through this ligament.

Ovarian Histology

• Outermost covering: Ovarian (germinal) epithelium, which is the visceral peritoneum.
• Tunica albuginea: Capsule of dense fibrous connective tissue.
• Ovary itself:
  • Cortex: Outer, dense region containing follicles with oocytes.
  • Medulla: Inner, looser region containing blood vessels, nerves, and lymphatic vessels.
  • Stroma: Connective tissue of the ovary.

Oogenesis and Fertilization

• Oogenesis: Production of a secondary oocyte in the ovaries.
• Oogonia: Cells from which oocytes develop. They divide by mitosis to produce more oogonia and primary oocytes.
• Prenatal oocyte production: Approximately 5 million oocytes are produced by the fourth month of prenatal life. About 2 million begin the first meiotic division but stop at prophase. They remain in this state until puberty.
• Primordial follicle: A primary oocyte surrounded by granulosa cells.
• Primary follicle: Formed when the oocyte and granular cells enlarge.
• Secondary follicle: Develops from the primary follicle and enlarges to form a mature or Graafian follicle.
• Ovulation: Typically, only one mature follicle is ovulated; the others degenerate.

Oogenesis Process

1. Mitosis: During development, oogonia increase in number through mitosis.
2. Differentiation: Before birth, most oogonia differentiate into primary oocytes.
3. Meiosis I: Primary oocytes (diploid cells) begin meiosis I, but the process halts at prophase I.
4. Puberty: Primary oocytes re-enter and complete meiosis I just before ovulation. Cytoplasm is split unevenly, with most remaining in the secondary oocyte. The smaller first polar body has less cytoplasm and either degenerates or divides into second polar bodies, which also eventually degenerate.
5. Ovulation and Meiosis II: Ovulation is the release of a secondary oocyte. The secondary oocyte begins meiosis II but stalls at metaphase II unless fertilization occurs. Fertilization is when a sperm cell binds to and penetrates the plasma membrane of the secondary oocyte. The secondary oocyte completes meiosis II, forming two cells, each containing 23 chromosomes. One is the second polar body, which degenerates, and the other is the larger ovum.

Ovulation, Fertilization, and Follicle Fate

• Ovulation: Release of a secondary oocyte from an ovary. Cytoplasmic division during meiosis is uneven, resulting in a large oocyte and very small polar bodies.
• Corpus luteum: The Graafian follicle becomes the corpus luteum.
• Fertilization: Starts when a sperm cell binds to the plasma membrane of the secondary oocyte and penetrates the cytoplasm.
• Meiosis II completion: The secondary oocyte completes meiosis II, forming one polar body, and the fertilized egg becomes a zygote.
• Fate of corpus luteum:
  • If fertilization occurs, the corpus luteum persists.
  • If no fertilization occurs, it becomes the corpus albicans.

Oogenesis and Follicle Development

1. Prenatal Development: Oogenesis begins when a female is in her mother’s uterus. Primary oocytes are located in primordial follicles, which consist of a primary oocyte surrounded by a single layer of flat granulosa cells.
2. Primary Oocyte Count: At birth, a female has about 2 million primary oocytes. This number decreases to around 300,000 to 400,000 by puberty. On average, about 400 primary oocytes complete development and give rise to secondary oocytes.
3. Development into Primary Follicles: At puberty, some primordial follicles become primary follicles as the oocyte enlarges, and the single layer of granulosa cells becomes thicker and cuboidal. A zona pellucida is deposited around the primary oocyte.
4. Secondary Follicle Formation: Approximately every 28 days, hormonal changes stimulate some primary follicles to develop further into secondary follicles. Fluid-filled spaces called vesicles form among the granulosa cells, and a capsule called the theca forms around the follicle. The theca interna cells surround the granulosa cells and participate in ovarian hormone synthesis. The theca externa is primarily connective tissue that merges with the stroma of the ovary.
5. Mature Follicle (Graafian Follicle): The secondary follicle continues to enlarge. When the fluid-filled vesicles fuse to form a single chamber called the antrum, it becomes a mature follicle or Graafian follicle. The oocyte is pushed to one side and lies in a mass of granulosa cells called the cumulus cells or cumulus oophorus.
6. Ovulation: The mature follicle forms a lump on the surface of the ovary. During ovulation, the follicle ruptures, releasing blood, follicular fluid, and the oocyte, surrounded by cumulus cells, into the peritoneal cavity. The cumulus cells form the corona radiata. Usually, only one mature follicle reaches the most advanced stages and is ovulated, while other follicles degenerate through a process called atresia.
7. Corpus Luteum Formation: After ovulation, the ruptured mature follicle transforms into an endocrine structure called the corpus luteum. This structure has a convoluted appearance due to its collapse after ovulation. The granulosa cells and the theca interna, now called luteal cells, enlarge and secrete hormones—progesterone and smaller amounts of estrogen. If pregnancy occurs, the corpus luteum enlarges and remains active, particularly during the first trimester, becoming the corpus luteum of pregnancy.
8. Corpus Albicans Formation: If pregnancy does not occur, the corpus luteum remains functional for about 10–12 days and then begins to degenerate. As it degenerates, progesterone and estrogen secretion decreases. Connective tissue cells within the corpus luteum enlarge and become clear, giving the structure a whitish color, and it is then called the corpus albicans. The corpus albicans continues to shrink and eventually disappears after several months or years.

Uterine Tubes

• Nomenclature: Uterine tube = fallopian tube = oviduct.
• Mesosalpinx: Part of the broad ligament directly associated with the uterine tube.
• Function: Open directly into the peritoneal cavity to receive the oocyte from the ovary. Transport oocyte or zygote from the ovary to the uterus.
• Fimbriae: Long, thin processes extending from the infundibulum. The inner surface is ciliated. The infundibulum is open to the peritoneal cavity.
• Ampulla: Widest part of the uterine tube, where fertilization typically occurs.
• Layers: Outer serosa, middle muscular layer, and inner mucosa. The mucosa consists of simple ciliated columnar epithelium with longitudinal folds.
• Nutrient provision: Provides nutrients for the oocyte/embryonic mass.
• Cilia movement: Cilia move fluid and the oocyte/embryonic mass through the tube toward the uterus.

Uterus

• Parts: Body, isthmus, cervix, and fundus.
• Ligaments: Broad, round, and uterosacral ligaments.
  • Round ligament: Extends from the uterus through the inguinal canals to the labia majora.
  • Uterosacral ligament: Attaches the lateral wall of the uterus to the sacrum.
• Layers: Composed of three layers:
  • Perimetrium: Serous membrane.
  • Myometrium: Smooth muscle layer.
  • Endometrium: Mucous membrane.
    • Functional layer: Innermost layer that is replaced during the menstrual cycle. Supplied by spiral arteries.
    • Basal layer: Deepest layer.
• Cervix: More rigid and less contractile than the rest of the uterus.
  • Cervical canal: Lined with mucous glands. Contains a mucous plug, except near ovulation when the secretion consistency changes to seromucous.

Vagina

• Function: Female organ of copulation. Allows menstrual flow and childbirth.
• Hymen: Covers the vaginal opening or orifice.
• Structure: Muscular walls with a mucous membrane lining (moist stratified squamous epithelium).
• Features: Longitudinal columns and transverse rugae.
• Fornix: Superior portion attached to the sides of the cervix.

Female External Genitalia

• Vulva: Also known as the pudendum or external female genitalia.
• Vestibule: Space in the vulva.
• Labia minora: Form borders on the sides of the vestibule.
• Clitoris: Erectile structure.
  • Corpora cavernosa: Expanded at the bases to form the crus of the clitoris.
  • Corpora spongiosa: Erectile tissue in the clitoris.
• Labia majora: Unite to form the mons pubis.
• Vaginal orifice: Located in the lateral margins, containing erectile tissue called the bulb of the vestibule (homologous to the corpus spongiosum in males).
• Vestibular Glands: Glands within the vestibule that produce fluid to moisten the area
  • Greater vestibular gland
  • Lesser vestibular glands
  • Paraurethral glands
• Labia Majora: Rounded folds of skin on either side of the labia minora; conceal the contents of the pudenda
  • Medial surfaces covered with numerous sebaceous and sweat glands
• Pudendal Cleft: Space between the labia majora
• Mons Pubis: Anteriorly, the labia majora merge in an elevated area over the symphysis pubis

Perineum

• Analogous to the male perineum, divided into:
  • Anterior urogenital triangle
  • Posterior anal triangle
• Clinical perineum: Region between the vagina and anus.
  • Skin in this area can tear during childbirth.
  • Episiotomy: Incision in the clinical perineum to aid in childbirth.

Mammary Glands

• Function: Organs of milk production located within the breasts.
• Composition: Consist of glandular lobes of modified sweat glands and adipose tissue.
• External structures: Raised nipple surrounded by the pigmented areola, which contains areolar glands that lubricate and protect the nipple and areola.
• Support: Cooper ligaments support the breasts.
• Structure: Adult female mammary gland consists of 15 to 20 lobes surrounded by fat; each lobe has a single lactiferous duct that enlarges into a lactiferous sinus for milk storage.
• Lactiferous duct: Supplies a lobe and subdivides into smaller ducts supplying a lobule that expands to form alveoli.
• Myoepithelial cells: Surround the alveoli and contract to expel milk.
• Gynecomastia: Breast development in a male.

Physiology of Female Reproduction

• Puberty: Begins with menarche (first episode of menstrual bleeding).
  • Begins when GnRH levels increase, as well as LH and FSH.
• Menstrual Cycle: Changes in the uterus
  • About 28 days long on average.
• Ovarian cycle: Changes in ovaries.
• Uterine cycle: Changes in the uterus.
• Amenorrhea: Absence of a menstrual cycle.
• Menopause: Cessation of menstrual cycles.

Major Reproductive Hormones and Their Effects in Females

Ovarian Cycle

• Follicular Phase (Days 1-14):
  • Occurs before ovulation.
  • A primordial follicle develops into a mature follicle as the primary oocyte undergoes meiosis I.
  • Follicle development is stimulated by FSH from the pituitary gland.
  • Follicles release estrogen, leading to a surge of LH and ovulation, and also causing proliferation of the uterine endometrium.
• Luteal Phase (Days 15-28):
  • Occurs after ovulation.
  • Following ovulation, the follicle forms the corpus luteum, which secretes estrogen and progesterone. Progesterone causes the uterine endometrium to thicken and secrete fluid.
  • At the end of the luteal phase (if no fertilization), the corpus luteum degenerates, progesterone levels drop, and the endometrium is shed (menses).
  • If fertilization occurs, hCG production keeps the corpus luteum alive.

Regulation of Hormone Secretion During the Ovarian Cycle

1. Hypothalamic Secretion: Early in the ovarian cycle, the hypothalamus increases the release of GnRH. Additionally, the anterior pituitary's sensitivity to GnRH increases.
2. Anterior Pituitary Gland Secretion: As a result of increased GnRH secretion, the anterior pituitary increases the secretion of FSH and LH.
3. Follicular Phase of Ovarian Cycle Begins: FSH and LH stimulate the growth and maturation of ovarian follicles. FSH is primarily responsible for initiating the development of the primary follicles, and as many as 25 follicles begin to mature during each ovarian cycle. However, normally only 1 is ovulated. The follicles that start to develop in response to FSH may not ovulate during the same ovarian cycle in which they begin to mature but may ovulate one or two cycles later. The remaining follicles degenerate.
4. Effects of Estrogen Secretion: As follicles mature, they begin to secrete estrogens. Estrogen secretion by the follicle has three major effects:
   • (a) Stimulation of uterine endometrial proliferation
   • (b) Positive feedback on hypothalamic and anterior pituitary secretion
   • (c) Determination of which follicles degenerate. Larger, more mature follicles appear to secrete estrogen and other substances that have an inhibitory effect on other, less mature follicles.
5. LH Surge and FSH Surge: Estrogen has a positive-feedback effect on the hypothalamus and anterior pituitary, resulting in an increase in the secretion of both LH and FSH, often referred to as the LH surge and FSH surge. The LH surge occurs several hours earlier and to a greater degree than the FSH surge, and the L H surge can last up to 24 hours.
6. Ovulation and Luteal Phase of Ovarian Cycle Begins: The LH surge stimulates the maturation of the follicle, including completion of meiosis I by the primary oocyte. Also, the LH surge triggers several events that are very much like inflammation in a mature follicle. These events result in ovulation, which involves the rupturing of the follicle and the release of the oocyte and corona radiata.
7. Formation of Corpus Luteum: Shortly after ovulation, the follicle’s production of estrogen decreases, the remaining cells of the follicle differentiate into corpus luteum cells and begin to secrete progesterone and estrogen. Progesterone and estrogen secretion stimulate further development of the uterine endometrium.
8. Negative-Feedback Effect of Progesterone and Estrogen Secretion: The increased progesterone and estrogen levels now have a negative-feedback effect on the hypothalamus and anterior pituitary, resulting in a decrease in FSH and LH secretion.

Uterine Cycle

1. Menses: A period of mild hemorrhage that occurs approximately once each month, during which the functional layer of the endometrium is sloughed and expelled from the uterus. Menstruation is the discharge of the sloughed endometrial tissue and blood.
2. Proliferative Phase: The time between the ending of menses and ovulation. During this phase, the endometrium of the uterus begins to regenerate. The remaining epithelial cells rapidly divide and replace the cells of the functional layer that was sloughed during the last menses. A relatively uniform layer of low cuboidal endometrial cells is produced. The cells later become columnar, and the layer of cells folds to form tubular spiral glands. Blood vessels called spiral arteries project through the delicate connective tissue that separates the individual spiral glands to supply nutrients to the endometrial cells.
3. Secretory Phase: The period after ovulation and before the next menses, marked by the maturation of and secretion by spiral glands. During the secretory phase, the endometrium becomes thicker, and the spiral glands develop to a greater extent and begin to secrete small amounts of a fluid rich in glycogen. Approximately 7 days after ovulation, or about day 21 of the menstrual cycle, the endometrium is prepared to receive a developing embryonic mass if fertilization has occurred. If the developing embryonic mass arrives in the uterus too early or too late, the endometrium does not provide a suitable environment.

Events During the Menstrual Cycle

Female Sexual Behavior and Sex Act

• Female sexual behavior:
  • Depends on hormones: androgens and steroids.
  • Depends on psychological factors.
• Female sex act:
  • Parasympathetic stimulation.
  • Blood engorgement in the clitoris and around the vaginal opening.
  • Erect nipples.
  • Mucous-like fluid extruded into the vagina and through the wall.
  • Orgasm not necessary for fertilization to occur.

Female Fertility and Pregnancy

• Female fertility:
  • Sperm is ejaculated into the vagina during copulation and transported through the cervix and uterine tubes to the ampulla.
  • Sperm cells undergo capacitation, enabling them to release acrosomal enzymes to digest away follicular cells.
• Pregnancy:
  • The oocyte can be fertilized up to 24 hours after ovulation.
  • Sperm cells can be viable for up to 6 days in the female tract.
  • Ectopic pregnancy: Implantation occurs anywhere other than the uterine cavity.
• Fertilization:
  • Occurs in the uterine tube. Multiple mitoses occur after the union of oocyte and sperm nuclei (pronuclei), forming an embryo. The outer layer of the embryonic mass is the trophoblast.
  • The trophoblast secretes proteolytic enzymes to digest the thickened endometrium.
  • Implantation: The trophoblast also secretes HCG.

Hormone Changes During Pregnancy

• Human chorionic gonadotropin (hCG):
  • Produced by the embryo soon after fertilization and throughout the first trimester.
• Placenta Development:
  • The placenta develops and produces progesterone and estrogen in increasing levels throughout pregnancy.

1. The embryo and developing placenta secrete hCG, which is transported in the blood to the ovary and causes the corpus luteum to remain functional. As a consequence, both estrogen and progesterone levels continue to increase rather than decrease. The secretion of hCG increases rapidly and reaches a peak about 8 to 9 weeks after fertilization. Subsequently, hCG levels in the circulatory system have declined to a lower level by 16 weeks and remain at a relatively constant level throughout the remainder of pregnancy. The detection of hCG in the urine is the basis for some pregnancy tests.
2. Progesterone secretion increases during most of the pregnancy until it levels off near the end of the third trimester.
3. Estrogen levels increase slowly throughout pregnancy, with a more rapid increase as the time of birth approaches.

Menopause

• Age of onset: 40 to 50 years old.
• Changes: Menstrual periods become less regular, and ovulation stops. This phase is known as the female climacteric (perimenopause).
• Definition: Cessation of menstrual cycles = menopause.
• Hormone Levels: LH and FSH are elevated, but the few remaining follicles become insensitive to LH and FSH.
• Ovarian Function: Ovaries stop producing estrogen and progesterone.
• Symptoms: hot flashes, irritability, night sweats, fatigue, anxiety, and occasionally severe emotional disturbances.

Possible Changes Caused by Decreased Ovarian Hormone Secretion in Postmenopausal Females

Effects of Aging on the Reproductive System

Males

• Testes may decrease in size in some individuals.
• Decrease in the number of interstitial cells and thinning of the walls of seminiferous tubules.
• Decrease in the rate of sperm cell production.
• Prostate: Decrease in blood flow, increase in the thickness of the epithelial lining, and decrease in functional smooth muscle cells. Possible benign prostatic hypertrophy.
• Impotence or a decrease in sexual performance/activity.

Females

• Menopause.
• Changes in the uterine position may lead to prolapse.
• The uterus decreases by 50% in size within 15 years after menopause.
• Vaginal wall: Thinner, less elastic, and less lubrication. Increased incidence of vaginal infections.
• Sexual excitement requires greater time to develop; the peak is lower, and the return to the resting state is quicker.
• Increased risk of breast, endometrial, cervical, and ovarian cancer.

Representative Diseases and Disorders of the Reproductive System

Birth Control Methods

Long-lasting Reversible Contraception

• Intrauterine device (IUD): Copper IUD or synthetic progesterone-coated or levonorgestrel-releasing (LNG-IUD). Works by preventing fertilization.
• Birth control implant: A capsule implanted under the skin of the upper arm containing etonogestrel or synthetic progesterone; prevents sperm from entering the uterus by thickening the cervical mucus.

Permanent Methods of Birth Control

• Female sterilization: Tubal ligation; prevents fertilization.
• Male sterilization: Vasectomy; the vas deferens is cut so no sperm leave the male’s body.

Hormonal Methods of Birth Control

• Prevent ovulation.
• Injectables.
• Pills.
• Patch and vaginal ring.

Barrier Methods of Birth Control

• Prevent sperm and oocyte from meeting.
• Female condom.
• Male condom.
• Diaphragm.

Fertility-Awareness-Based Methods of Birth Control

• Tracking fertile days.
• Standard days method.
• Two-day method – monitor cervical mucus traits.

Emergency Contraception

• After unprotected intercourse – emergency contraceptive pills (morning after or week after), insertion of copper IUD.

Traditional Methods of Birth Control

• Withdrawal.
• Rhythm method (calendar).
• Abstinence.