Human Reproduction: A Summary for Revision

1. Introduction to Human Reproduction

Humans are sexually reproducing and viviparous [1, 2]. Key reproductive events occur after puberty and include:

• Gametogenesis: Formation of gametes (sperms in males, ovum in females) [1, 3].
• Insemination: Transfer of sperms into the female genital tract [1, 4].
• Fertilisation: Fusion of male and female gametes, forming a zygote [1, 5].
• Implantation: Formation and development of a blastocyst and its attachment to the uterine wall [1, 6].
• Gestation: Embryonic development (pregnancy) [1, 7].
• Parturition: Delivery of the baby [8, 9].

Key difference: Sperm formation continues in old men, but ovum formation ceases in women around 50 years of age (menopause) [8, 10].

2. The Male Reproductive System

Located in the pelvis region .

2.1 Components:

• A pair of testes .
• Accessory ducts .
• Glands .
• External genitalia .

2.2 Testes:

• Situated outside the abdominal cavity within a pouch called the scrotum .
• Scrotum function: Helps maintain a low temperature (2-2.5°C lower than normal body temperature) necessary for spermatogenesis .
• Structure: Oval shape, about 4-5 cm length, 2-3 cm width . Covered by a dense covering .
• Testicular Lobules: Each testis has ~250 compartments .
• Seminiferous Tubules: Each lobule contains 1-3 highly coiled tubules where sperms are produced .
  • Lined by two cell types:
    • Male germ cells (spermatogonia): Undergo meiotic divisions leading to sperm formation [12, 13].
    • Sertoli cells: Provide nutrition to the germ cells .
• Interstitial Spaces (outside seminiferous tubules):
  • Contain small blood vessels and interstitial cells or Leydig cells .
  • Leydig cells function: Synthesise and secrete testicular hormones called androgens [13, 14].
  • Also contain other immunologically competent cells .

2.3 Male Sex Accessory Ducts:

• Include rete testis, vasa efferentia, epididymis, and vas deferens .
• Pathway of sperm transport: Seminiferous tubules → rete testis → vasa efferentia → epididymis → vas deferens .
• Vas deferens: Ascends to the abdomen, loops over the urinary bladder, receives a duct from a seminal vesicle, and opens into the urethra as the ejaculatory duct .
• Function: Store and transport sperms from the testis to the outside through the urethra .
• Urethra: Originates from the urinary bladder, extends through the penis to its external opening (urethral meatus) [15, 16].

2.4 External Genitalia (Penis):

• Male external genitalia .
• Made of special tissue for erection to facilitate insemination .
• Glans penis: Enlarged end, covered by a loose fold of skin called foreskin [16, 17].

2.5 Male Accessory Glands:

• Paired seminal vesicles .
• A prostate gland .
• Paired bulbourethral glands .
• Secretions: Constitute the seminal plasma .
  • Seminal plasma content: Rich in fructose, calcium, and certain enzymes .
  • Bulbourethral glands: Secretions also help in lubrication of the penis .
• Function of ducts and glands: Store and transport sperms; secretions are essential for maturation and motility of sperms .
• Semen: Seminal plasma along with sperms .
• Maintenance: Functions are maintained by testicular hormones (androgens) .

3. The Female Reproductive System

Located in the pelvic region .

3.1 Components:

• A pair of ovaries .
• A pair of oviducts (fallopian tubes) [17, 21].
• Uterus .
• Cervix .
• Vagina .
• External genitalia .
• A pair of mammary glands (structurally and functionally integrated) [20, 22].

3.2 Ovaries:

• Primary female sex organs .
• Function: Produce the female gamete (ovum) and several steroid hormones (ovarian hormones) [20, 23].
• Location: One on each side of the lower abdomen .
• Size: About 2-4 cm in length .
• Connection: Connected to the pelvic wall and uterus by ligaments .
• Structure: Covered by a thin epithelium enclosing the ovarian stroma [20, 21].
  • Stroma divided into a peripheral cortex and an inner medulla .

3.3 Female Accessory Ducts:

• Oviducts (Fallopian Tubes): About 10-12 cm long, extend from ovary to uterus .
  • Infundibulum: Funnel-shaped part closer to the ovary .
  • Fimbriae: Finger-like projections on infundibulum edges, help in collection of the ovum after ovulation [14, 21].
  • Ampulla: Wider part of the oviduct, where fertilisation usually occurs [4, 24].
  • Isthmus: Last part, narrow lumen, joins the uterus .
• Uterus (Womb): Single, inverted pear shape . Supported by ligaments .
  • Uterine Wall Layers:
    • Perimetrium: External thin membranous layer .
    • Myometrium: Middle thick layer of smooth muscle, exhibits strong contraction during delivery [14, 25].
    • Endometrium: Inner glandular layer lining uterine cavity, undergoes cyclical changes during menstrual cycle [14, 25].
• Cervix: Narrow opening of the uterus into the vagina .
  • Cervical Canal: Cavity of the cervix .
• Vagina: Along with the cervical canal, forms the birth canal .

3.4 Female External Genitalia:

• Include mons pubis, labia majora, labia minora, hymen, and clitoris .
• Mons pubis: Cushion of fatty tissue covered by skin and pubic hair .
• Labia majora: Fleshy folds extending from mons pubis, surrounding vaginal opening .
• Labia minora: Paired folds under labia majora .
• Hymen: Membrane partially covering vaginal opening, can be torn by various activities (first coitus, fall, tampon insertion, sports) [26, 27]. Not a reliable indicator of virginity [14, 27].
• Clitoris: Tiny finger-like structure above urethral opening, at upper junction of labia minora .

3.5 Mammary Glands:

• Characteristic of all female mammals .
• Paired structures (breasts) containing glandular tissue and fat .
• Glandular tissue: Divided into 15-20 mammary lobes, each containing clusters of cells called alveoli .
  • Alveoli function: Secrete milk, which is stored in their lumens .
• Duct System: Alveoli → mammary tubules → mammary duct → wider mammary ampulla → lactiferous duct → opens at the nipple for milk expression during breastfeeding [3, 22].

4. Gametogenesis

The process of gamete formation by primary sex organs .

4.1 Spermatogenesis (Sperm Formation in Testis):

• Initiated at puberty .
• Hormonal Regulation:
  • Increased Gonadotropin Releasing Hormone (GnRH) from hypothalamus .
  • GnRH acts on anterior pituitary, stimulating Luteinising Hormone (LH) and Follicle Stimulating Hormone (FSH) secretion .
  • LH: Acts on Leydig cells, stimulating synthesis and secretion of androgens, which in turn stimulate spermatogenesis .
  • FSH: Acts on Sertoli cells, stimulating secretion of factors that help in spermiogenesis .
• Process:
  1. Spermatogonia (immature male germ cells, diploid, 46 chromosomes) multiply by mitotic division [3, 30].
  2. Some spermatogonia become primary spermatocytes .
  3. Primary spermatocytes undergo Meiosis I (reduction division) → two equal, haploid secondary spermatocytes (23 chromosomes each) .
  4. Secondary spermatocytes undergo Meiosis II → four equal, haploid spermatids [28, 30].
  5. Spermiogenesis: Spermatids transform into spermatozoa (sperms) .
  6. Spermiation: After spermiogenesis, sperm heads embed in Sertoli cells and are finally released from seminiferous tubules .

4.2 Structure of a Sperm:

• Microscopic structure composed of a head, neck, middle piece, and tail .
• Enveloped by a plasma membrane .
• Head: Contains an elongated haploid nucleus .
  • Anterior portion covered by a cap-like structure, acrosome .
  • Acrosome function: Filled with enzymes that help fertilisation of the ovum [14, 31].
• Middle Piece: Possesses numerous mitochondria, which produce energy for tail movement .
• Tail: Facilitates sperm motility, essential for fertilisation [14, 31].
• Normal Fertility: For normal fertility, at least 60% of 200-300 million ejaculated sperms must have normal shape/size, and 40% must show vigorous motility .

4.3 Oogenesis (Ovum Formation in Ovary):

• Markedly different from spermatogenesis .
• Initiation: Begins during embryonic development stage .
  • A couple of million gamete mother cells (oogonia) are formed within each fetal ovary; no more oogonia are formed after birth .
• Process:
  1. Oogonia start division and enter prophase-I of meiotic division, becoming temporarily arrested as primary oocytes .
  2. Each primary oocyte gets surrounded by a layer of granulosa cells, forming a primary follicle .
  3. Many follicles degenerate from birth to puberty; only 60,000-80,000 primary follicles remain per ovary at puberty .
  4. Primary follicles get surrounded by more granulosa layers and a new theca, becoming secondary follicles .
  5. Secondary follicle transforms into a tertiary follicle, characterised by a fluid-filled cavity called antrum . The theca layer organises into inner theca interna and outer theca externa .
  6. At the tertiary follicle stage, the primary oocyte within it grows in size and completes its first meiotic division .
     • This is an unequal division, resulting in a large haploid secondary oocyte (retains bulk of nutrient-rich cytoplasm) and a tiny first polar body [33, 34].
  7. The tertiary follicle further changes into the mature follicle or Graafian follicle .
  8. The secondary oocyte forms a new membrane around it called zona pellucida .
  9. Ovulation: The Graafian follicle ruptures to release the secondary oocyte (ovum) from the ovary [2, 35].

5. Menstrual Cycle

The reproductive cycle in female primates (monkeys, apes, humans) .

• Menarche: The first menstruation, beginning at puberty .
• Menopause: Menstrual cycles cease around 50 years of age .
• Duration: Average interval of about 28/29 days .
• Ovulation: One ovum is released during the middle of each cycle (around day 14) .
• Regulation: Cyclical changes in the ovary and uterus are induced by changes in levels of pituitary and ovarian hormones [37, 38].

5.1 Phases of the Menstrual Cycle:

• 1. Menstrual Phase (Day 1-5):
  • Menstrual flow occurs .
  • Results from breakdown of the endometrial lining of the uterus and its blood vessels .
  • Occurs only if the released ovum is not fertilised .
  • Lack of menstruation can indicate pregnancy, but also stress, poor health, etc. .
• 2. Follicular Phase (Proliferative Phase):
  • Follows menstrual phase .
  • Primary follicles in the ovary grow to become a fully mature Graafian follicle .
  • Simultaneously, the endometrium of the uterus regenerates through proliferation .
  • Hormone changes:
    • Secretion of gonadotropins (LH and FSH) increases gradually .
    • Stimulates follicular development and secretion of estrogens by growing follicles .
• 3. Ovulatory Phase (around Day 14):
  • Both LH and FSH attain a peak level in the middle of the cycle .
  • LH Surge: Rapid secretion of LH leading to its maximum level .
  • Induces rupture of Graafian follicle and release of ovum (ovulation) [2, 40].
• 4. Luteal Phase (Secretory Phase):
  • Follows ovulation .
  • Remaining parts of the Graafian follicle transform into the corpus luteum [14, 40].
  • Corpus luteum function: Secretes large amounts of progesterone, which is essential for maintenance of the endometrium [14, 40].
  • This endometrium is necessary for implantation of the fertilised ovum and pregnancy .
  • During pregnancy, all menstrual cycle events stop and there is no menstruation [10, 14].
  • If fertilisation does not occur: The corpus luteum degenerates, causing disintegration of the endometrium, leading to menstruation and marking a new cycle .

5.2 Menstrual Hygiene:

• Maintaining hygiene and sanitation is important during menstruation .
• Includes regular bathing, use of sanitary napkins/clean pads, changing them every 4-5 hours, and proper disposal .

6. Fertilisation and Implantation

6.1 Fertilisation:

• Insemination: Semen is released by the penis into the vagina during copulation .
• Sperm Transport: Motile sperms rapidly swim through the cervix, enter the uterus, and finally reach the ampullary region of the fallopian tube .
• Ovum Transport: The ovum released from the ovary is also transported to the ampullary region .
• Occurrence: Fertilisation can only occur if the ovum and sperms are transported simultaneously to the ampullary region [4, 41].
• Process of fusion:
  1. A sperm contacts the zona pellucida layer of the ovum .
  2. This induces changes in the membrane that block the entry of additional sperms, ensuring only one sperm fertilises the ovum .
  3. Secretions of the acrosome help the sperm enter the ovum’s cytoplasm .
  4. This entry induces the completion of the meiotic division of the secondary oocyte .
     • This second meiotic division is unequal, forming a second polar body and a haploid ovum (ootid) .
  5. The haploid nuclei of the sperm and ovum fuse to form a diploid zygote [41, 42].

6.2 Sex Determination:

• The sex of the baby is decided at the stage of fertilisation .
• Female chromosome pattern: XX; Male chromosome pattern: XY .
• Female gametes (ova) always carry X chromosome .
• Male gametes (sperms) carry either X (50%) or Y (50%) chromosome .
• Zygote:
  • XX: Develops into a female baby (if an X-sperm fertilises the ovum) [43, 44].
  • XY: Develops into a male baby (if a Y-sperm fertilises the ovum) [43, 44].
• Conclusion: Scientifically, the sex of the baby is determined by the father, not the mother .

6.3 Implantation:

• Cleavage: The zygote undergoes repeated mitotic division (called cleavage) as it moves through the isthmus towards the uterus .
  • Forms 2, 4, 8, 16 daughter cells called blastomeres .
• Morula: The embryo with 8 to 16 blastomeres .
• Blastocyst: The morula continues to divide and transforms into a blastocyst as it moves further into the uterus [41, 45].
  • Blastomeres in blastocyst: Arranged into an outer layer called trophoblast and an inner group of cells (attached to trophoblast) called the inner cell mass .
• Attachment and Embedding:
  1. The trophoblast layer attaches to the endometrium .
  2. The inner cell mass differentiates as the embryo .
  3. Uterine cells divide rapidly, covering the blastocyst [6, 45].
  4. Result: The blastocyst becomes embedded in the endometrium of the uterus .
• Implantation leads to pregnancy [6, 38].

7. Pregnancy and Embryonic Development

7.1 Placenta:

• After implantation, finger-like projections (chorionic villi) appear on the trophoblast .
• These villi are surrounded by uterine tissue and maternal blood .
• Formation: Chorionic villi and uterine tissue interdigitate, forming a structural and functional unit called the placenta [41, 46].
• Functions:
  • Facilitates supply of oxygen and nutrients to the embryo .
  • Removes carbon dioxide and excretory/waste materials produced by the embryo .
  • Connected to the embryo through an umbilical cord, which aids substance transport .
• Endocrine Tissue: Placenta acts as an endocrine tissue, producing several hormones :
  • Human chorionic gonadotropin (hCG) .
  • Human placental lactogen (hPL) .
  • Estrogens .
  • Progestogens .
• Other Hormones during Pregnancy:
  • Relaxin (secreted by the ovary in later pregnancy) .
  • hCG, hPL, and relaxin are produced only during pregnancy .
  • Levels of estrogens, progestogens, cortisol, prolactin, thyroxine increase several-fold in maternal blood .
  • These increased hormones are essential for supporting fetal growth, metabolic changes in the mother, and maintenance of pregnancy .

7.2 Embryonic Development:

• Germ Layers: Immediately after implantation, the inner cell mass (embryo) differentiates into:
  • Ectoderm (outer layer) .
  • Endoderm (inner layer) .
  • Mesoderm (soon appears between ectoderm and end) .
  • These three germ layers give rise to all tissues and organs in adults .
• Stem Cells: The inner cell mass contains stem cells with the potency to give rise to all tissues and organs .
• Gestation Period: Human pregnancy lasts approximately 9 months [7, 49].
• Major Developmental Milestones:
  • After 1 month: Embryo’s heart is formed (first sign noticed by stethoscope) .
  • End of 2nd month: Foetus develops limbs and digits .
  • End of 12 weeks (First Trimester): Most major organ systems are formed, limbs and external genital organs are well-developed .
  • 5th month: First movements of the foetus and appearance of hair on the head .
  • End of 24 weeks (End of Second Trimester): Body covered with fine hair, eyelids separate, eyelashes formed .
  • End of 9 months: Foetus is fully developed and ready for delivery [7, 38].

8. Parturition and Lactation

8.1 Parturition (Childbirth):

• The process of delivery of the foetus (childbirth) [9, 38].
• Average duration of human pregnancy is about 9 months (gestation period) .
• Induced by a complex neuroendocrine mechanism [9, 38].
• Mechanism:
  1. Signals originate from the fully developed foetus and the placenta .
  2. These induce mild uterine contractions called foetal ejection reflex .
  3. This reflex triggers the release of oxytocin from the maternal pituitary .
  4. Oxytocin acts on the uterine muscle, causing stronger uterine contractions .
  5. Stronger contractions stimulate further oxytocin secretion, creating a positive feedback loop .
  6. This leads to increasingly stronger contractions, expelling the baby out of the uterus through the birth canal .
  7. Soon after the infant, the placenta is also expelled .

8.2 Lactation:

• The mammary glands undergo differentiation during pregnancy and start producing milk towards the end of pregnancy [50, 51].
• This process is called lactation and helps the mother feed the newborn [38, 51].
• Colostrum: The milk produced during the initial few days of lactation .
  • Content: Contains several antibodies essential to develop resistance for the newborn .
• Importance: Doctors recommend breast-feeding during the initial period of infant growth for bringing up a healthy baby .