Male Mammalian Reproductive Physiology BZO5T12

Syllabus topics (RTMNU)

• Overview of mammalian reproductive system: General organization and functional significance of the male reproductive system in mammals
• Primary and secondary sex organs: Distinction between primary reproductive organs (testes) and secondary/accessory sex organs; their structural and functional roles
• Gross Anatomy of Male Reproductive Organs: Structure and organization of testes, seminiferous tubules, epididymis, and vas deferens; their role in sperm production and transport
• Accessory reproductive gland: Structure and functions of accessory glands (seminal vesicles, prostate gland, and bulbourethral glands); contribution to semen formation

Overview of Mammalian Male Reproductive System

The male reproductive system produces male gametes (spermatozoa) and male sex hormones (androgens, mainly testosterone), and delivers sperm into the female tract.

General organisation:

1. A pair of testes – in the scrotum.
2. Duct system – rete testis, efferent ductules, epididymis, vas deferens, ejaculatory duct and urethra.
3. Accessory glands – seminal vesicles, prostate and bulbourethral (Cowper's) glands.
4. External genitalia – penis (copulatory organ) and scrotum.

Functional significance: (1) spermatogenesis – continuous production of millions of sperm daily; (2) steroidogenesis – testosterone for male characters and libido; (3) maturation, storage and transport of sperm; (4) production of seminal fluid to nourish and protect sperm; (5) copulation and internal fertilisation, an adaptation for life on land.

Scrotum and temperature: In most mammals the testes descend into the scrotum because spermatogenesis needs a temperature about 2–3 °C lower than body temperature. This is maintained by the pampiniform plexus (a network of veins that cools arterial blood by counter-current heat exchange), the cremaster muscle (pulls testes up in cold) and the dartos muscle (wrinkles the scrotal skin). Failure of descent is cryptorchidism, which causes infertility. (Elephants and whales have internal testes.)

Primary and Secondary Sex Organs

Secondary sexual characters (not organs) – beard, deep voice, broad shoulders, muscle mass, body hair – are also produced by androgens.

Gross Anatomy of Male Reproductive Organs

Testis: Oval organ (in man about 4–5 cm long). Coverings from outside: tunica vaginalis (serous sac from peritoneum), tunica albuginea (tough white fibrous capsule) and tunica vasculosa (vascular layer). Septa from the tunica albuginea divide the testis into about 250 lobules, each with 1–4 highly coiled seminiferous tubules.

Seminiferous tubules (histology):

1. Lined by germinal epithelium with germ cells at different stages – spermatogonia near the basement membrane, then spermatocytes, spermatids and sperm towards the lumen.
2. Sertoli (sustentacular) cells – tall cells extending from base to lumen; nourish germ cells, form the blood–testis barrier by tight junctions, secrete androgen-binding protein (ABP), inhibin and tubular fluid, and phagocytose leftover cytoplasm (residual bodies).
3. Interstitial (Leydig) cells – in connective tissue between tubules, near blood vessels; secrete testosterone under LH.
4. Myoid cells around tubules contract to move sperm.

Duct pathway: seminiferous tubules → tubuli recti → rete testis → vasa efferentia (efferent ductules) → epididymis → vas deferens → ejaculatory duct → urethra.

1. Epididymis: a single, very long, tightly coiled tube (about 6 m in man) on the back of the testis; parts – head (caput), body (corpus), tail (cauda). Lined by pseudostratified columnar epithelium with stereocilia that absorb fluid. Function: maturation (sperm become motile and able to fertilise), concentration and storage (mainly in the cauda).
2. Vas deferens (ductus deferens): thick muscular tube (about 45 cm) running through the inguinal canal in the spermatic cord; its end is widened as the ampulla; joins the duct of the seminal vesicle to form the ejaculatory duct, which opens into the prostatic urethra. Strong peristaltic contractions propel sperm during ejaculation.
3. Urethra: common passage for urine and semen, running through the penis.

Accessory Reproductive Glands

Contribution to semen: Semen = sperm (less than 5% of volume, from testes and epididymis) + seminal plasma (from the accessory glands). Seminal plasma provides a medium for transport, energy (fructose), buffering against vaginal acidity (alkaline pH), and coagulation followed by liquefaction.

Likely exam questions

1. (Long, 8 marks) Describe the gross anatomy and histology of the testis with a labelled diagram.
2. (Long, 8 marks) Describe the structure and functions of the male accessory reproductive glands and their contribution to semen.
3. (Short, 4 marks) Distinguish between primary and secondary sex organs.
4. (Short, 4 marks) Write the functions of Sertoli cells.
5. (Short, 4 marks) Write a note on the epididymis.

Syllabus topics (RTMNU)

• Structure of Spermatozoon and Acrosome Reaction: Ultrastructure of sperm (head, middle piece, and tail)
• Role of acrosome reaction in fertilization
• Spermiogenesis and sperm maturation: Process of spermatogenesis in seminiferous tubules
• Stages of spermiogenesis
• Maturation and storage of sperm in epididymis
• Semen: Volume, composition, and physiological functions of semen
• Role of seminal plasma in sperm viability and transport
• Sperm motility and metabolism: Mechanism of sperm motility
• Energy sources and metabolic requirements for sperm function

Structure of Spermatozoon

A mammalian spermatozoon is a small, motile, haploid cell (human sperm about 50–60 µm long) with almost no cytoplasm. Parts:

1. Head: oval and flattened in man (sickle-shaped in rat and mouse). Contains a highly condensed nucleus (DNA packed with protamines instead of histones). The front two-thirds is covered by the acrosome – a cap-like vesicle formed from the Golgi apparatus, containing enzymes such as hyaluronidase and acrosin.
2. Neck: short; contains the proximal centriole (passed to the egg; forms the first spindle in many mammals) and the connecting piece.
3. Middle piece: contains the axial filament surrounded by a spiral sheath of mitochondria – the "power house" giving ATP for movement; ends at the annulus.
4. Tail (principal piece and end piece): the axoneme with the 9+2 arrangement of microtubules (from the distal centriole), surrounded by outer dense fibres and a fibrous sheath; the end piece has only the axoneme. The tail beats like a whip to move the sperm.

Acrosome Reaction and its Role in Fertilization

Before the acrosome reaction, sperm undergo capacitation in the female reproductive tract (hours): removal of cholesterol and surface coating proteins from the sperm membrane, rise in intracellular Ca²⁺ and cAMP, and hyperactivated motility.

Acrosome reaction: When the capacitated sperm binds to the zona pellucida (glycoprotein coat of the egg; ZP3 in mouse), Ca²⁺ enters the sperm and the outer acrosomal membrane fuses at many points with the sperm plasma membrane. The acrosomal enzymes are released by exocytosis.

1. Hyaluronidase helps the sperm pass through the corona radiata cells.
2. Acrosin and other proteases digest a path through the zona pellucida.
3. The inner acrosomal membrane is exposed; the sperm protein Izumo1 binds to the egg receptor Juno, allowing fusion of sperm and egg membranes.
4. Only acrosome-reacted sperm can fertilise; the reaction is species-specific, preventing cross-species fertilisation. The egg then blocks polyspermy (cortical reaction).

Spermatogenesis and Spermiogenesis

Spermatogenesis is the formation of spermatozoa from spermatogonia in the seminiferous tubules. It starts at puberty and continues throughout life. In man one full cycle takes about 64–74 days.

1. Multiplication phase: Spermatogonia (2n) near the basement membrane divide by mitosis. Some (type A) remain as stem cells; others (type B) go forward.
2. Growth phase: Type B spermatogonia grow into primary spermatocytes (2n).
3. Maturation phase: Primary spermatocyte → meiosis I → two secondary spermatocytes (n) → meiosis II → four spermatids (n). Germ cells stay joined by cytoplasmic bridges.
4. Spermiogenesis: Change of round spermatids into spermatozoa (no division).
5. Spermiation: Release of sperm from Sertoli cells into the lumen.

Stages of spermiogenesis:

1. Golgi phase: Golgi vesicles fuse to form the acrosomal vesicle; centrioles move to the opposite pole and start the flagellum.
2. Cap phase: The acrosomal vesicle spreads over the front of the nucleus as a cap.
3. Acrosome phase: Nucleus condenses and elongates (histones replaced by protamines); mitochondria gather around the beginning of the flagellum to form the middle piece; a microtubule sleeve (manchette) shapes the head.
4. Maturation phase: Extra cytoplasm is shed as the residual body and eaten by Sertoli cells; the sperm is released.

Maturation and storage in epididymis: Sperm leaving the testis cannot swim properly or fertilise. During passage through the epididymis (about 10–14 days in man) they gain progressive motility and fertilising ability, their membrane proteins and lipids change, chromatin is further stabilised (disulphide bonds) and a cytoplasmic droplet moves and is lost. Mature sperm are stored in the cauda epididymis, kept quiescent by the acidic, low-oxygen fluid; unused sperm are absorbed.

Semen: Volume, Composition and Functions

Semen is the fluid ejaculated by the male, made up of spermatozoa and seminal plasma.

1. Volume: In man usually about 2–5 mL per ejaculate (WHO lower reference limit 1.4 mL); bull about 5 mL, boar up to 250 mL.
2. pH: slightly alkaline, about 7.2–8.0.
3. Appearance: grey-white, viscous; coagulates after ejaculation and liquefies in 15–30 minutes (by PSA).
4. Composition of seminal plasma: water; fructose; prostaglandins; citric acid; zinc, calcium, magnesium; proteins and enzymes (PSA, acid phosphatase); semenogelins; buffers (bicarbonate, phosphate); antioxidants; small amounts of hormones.

Physiological functions of seminal plasma: (1) vehicle for transport of sperm; (2) source of energy (fructose); (3) buffers vaginal acidity, keeping sperm alive; (4) coagulation keeps semen in the vagina, then liquefaction frees sperm; (5) prostaglandins cause contractions of female tract; (6) antioxidants and zinc protect sperm DNA and kill bacteria; (7) proteins suppress immune attack on sperm in the female.

Sperm Motility and Metabolism

Mechanism of motility:

1. The axoneme has 9 outer doublet microtubules and 2 central singlets. Dynein arms on each doublet are ATPase motor proteins.
2. Dynein uses ATP to "walk" on the neighbouring doublet, causing the doublets to slide. Because the doublets are linked (nexin links, radial spokes), sliding is converted into bending.
3. Bending moves along the tail as a wave, pushing the sperm forward; outer dense fibres and fibrous sheath give stiffness.
4. Regulation: cAMP and protein kinase A activate motility; Ca²⁺ entering through CatSper channels causes hyperactivation in the female tract; low pH in the epididymis keeps sperm inactive.

Energy sources and metabolism:

1. Glycolysis (fructolysis): Sperm break down fructose (and glucose) from seminal plasma to produce ATP and lactic acid; glycolytic enzymes are bound to the fibrous sheath of the principal piece, supplying ATP along the tail.
2. Oxidative phosphorylation in middle-piece mitochondria uses pyruvate, lactate and fatty acids when oxygen is available.
3. Sperm have little stored food, so they depend on the external medium. Requirements: suitable temperature, pH around 7–8, osmotic balance, protection from oxidative stress (reactive oxygen species damage membranes and DNA).
4. For semen preservation (artificial insemination of cattle), metabolism is slowed by cooling and freezing in liquid nitrogen (−196 °C) with cryoprotectants like glycerol.

Likely exam questions

1. (Long, 8 marks) Describe the process of spermatogenesis and the stages of spermiogenesis.
2. (Long, 8 marks) Describe the ultrastructure of a mammalian spermatozoon and explain the acrosome reaction.
3. (Short, 4 marks) Write the composition and functions of semen.
4. (Short, 4 marks) Explain the mechanism of sperm motility.
5. (Short, 4 marks) Write a note on sperm maturation in the epididymis.

Syllabus topics (RTMNU)

• Causes of male infertility: Genetic, hormonal, environmental, and lifestyle factors affecting male fertility
• Semen analysis parameters: Basic parameters of semen analysis including sperm count, motility, morphology, and viability
• Male contraceptive methods: Overview of male contraceptive methods including barrier methods, hormonal approaches (introductory concept), and surgical sterilization (vasectomy)
• Reproductive Health and Sexually Transmitted Infections (STIs): Basic understanding of reproductive health
• Common STIs affecting male reproductive function and preventive measures

Causes of Male Infertility

Infertility is the failure of a couple to achieve pregnancy after 12 months or more of regular unprotected intercourse. The male factor contributes to about half of infertile couples.

1. Genetic factors:
   • Klinefelter syndrome (47,XXY) – small testes, azoospermia.
   • Y-chromosome microdeletions in the AZF (azoospermia factor) region – failure of spermatogenesis.
   • CFTR gene mutations (cystic fibrosis) – congenital absence of the vas deferens.
   • Chromosomal translocations; Kallmann syndrome (GnRH deficiency with loss of smell); androgen receptor defects.
2. Hormonal factors: hypogonadotropic hypogonadism (low GnRH/FSH/LH), hyperprolactinaemia, thyroid disorders, diabetes, excess oestrogen, anabolic steroid misuse (suppresses FSH and LH).
3. Testicular and anatomical factors: varicocele (dilated veins of the pampiniform plexus raising testis temperature – a common correctable cause), cryptorchidism, testicular injury or torsion, obstruction of ducts (after infection or surgery), mumps orchitis, erectile and ejaculatory problems, anti-sperm antibodies.
4. Environmental factors: heat (hot baths, tight clothing, laptops on lap, furnace work), radiation, pesticides, heavy metals (lead, cadmium), industrial chemicals, endocrine-disrupting chemicals (e.g. bisphenol A, phthalates), air pollution.
5. Lifestyle factors: smoking, alcohol, tobacco chewing, recreational drugs, obesity, poor diet, lack of sleep, stress, sexually transmitted infections, some medicines (chemotherapy).

Semen Analysis Parameters

Semen analysis is the first test of male fertility. A sample is collected by masturbation after 2–7 days of abstinence and examined within one hour. WHO laboratory manual (6th edition, 2021) lower reference limits:

1. Sperm count: counted in a haemocytometer (Neubauer chamber) after dilution.
2. Motility: graded as progressive, non-progressive and immotile on a warm slide.
3. Morphology: stained smear (Papanicolaou or Diff-Quik); defects of head, neck/midpiece and tail are noted.
4. Viability: eosin–nigrosin stain – dead sperm take up the pink stain, live ones remain unstained; also the hypo-osmotic swelling test.
5. Other: pH (≥7.2), liquefaction time, viscosity, white cells, fructose.

Male Contraceptive Methods

Contraception means preventing pregnancy. Methods for men:

1. Barrier method – condom: a thin latex/polyurethane sheath that collects semen and prevents sperm entering the vagina. Cheap, no side effects, easily available (free in government health centres), and the only method that also protects against STIs and HIV. Failure mainly due to wrong use or tearing.
2. Behavioural methods: withdrawal (coitus interruptus) and abstinence – high failure rate.
3. Hormonal approaches (introductory): giving testosterone (often with a progestin) suppresses GnRH, LH and FSH by negative feedback, so spermatogenesis stops (azoospermia) while blood androgen stays normal. Reversible after stopping. Trials include a testosterone–nestorone gel and male "pills" (e.g. DMAU). None is yet in routine use – check latest.
4. Non-hormonal research methods: India's RISUG (Reversible Inhibition of Sperm Under Guidance, developed with ICMR) – a polymer gel injected into the vas deferens that damages passing sperm; under advanced trials – check latest status.
5. Surgical sterilisation – vasectomy: both vasa deferentia are cut and tied (or sealed) through a small opening in the scrotum. No-scalpel vasectomy (NSV), promoted under India's family planning programme, uses a tiny puncture without stitches. Simple, safe, done under local anaesthesia in 10–15 minutes; does not affect hormones, erection or ejaculation (semen still forms but without sperm). Not effective at once – sperm stored beyond the cut remain for about 3 months, so another method is used until semen analysis shows no sperm. Considered permanent (reversal is difficult).

Reproductive Health and Sexually Transmitted Infections (STIs)

Reproductive health (WHO) means a state of complete physical, mental and social well-being in all matters related to the reproductive system – not merely absence of disease. It includes safe sex, ability to reproduce, freedom to decide, and access to information and services.

Preventive measures: (1) correct and consistent use of condoms; (2) a single faithful partner, avoiding unsafe sex; (3) vaccination – hepatitis B and HPV; (4) early testing and complete treatment of both partners (syndromic management in government STI clinics); (5) not sharing needles; (6) awareness and sex education; (7) personal hygiene and regular check-ups.

Likely exam questions

1. (Long, 8 marks) Explain the genetic, hormonal, environmental and lifestyle causes of male infertility.
2. (Long, 8 marks) Describe the parameters of semen analysis and give an account of male contraceptive methods.
3. (Short, 4 marks) Write a note on vasectomy.
4. (Short, 4 marks) Name any four STIs with their causative agents and effects on male reproduction.
5. (Short, 4 marks) Define oligozoospermia, asthenozoospermia, teratozoospermia and azoospermia.

Syllabus topics (RTMNU)

• Hypothalamic-pituitary-gonadal (HPG) axis: Organization and regulation of the HPG axis in males
• Role of Reproductive Hormones: Functions of GnRH, FSH, LH, testosterone, and inhibin in spermatogenesis and male reproductive physiology
• Mechanism of action of Androgens: Basic mechanism of androgen hormone action at the cellular level
• Puberty and Aging in Males: Hormonal and physiological changes during puberty
• Age-related changes in male reproductive function

Hypothalamic–Pituitary–Gonadal (HPG) Axis

The HPG axis is the chain of three endocrine levels – hypothalamus, anterior pituitary and testes – which controls male reproduction through hormones and feedback.

1. Hypothalamus: GnRH neurons release gonadotropin-releasing hormone (GnRH) in pulses (about one pulse every 1.5–2 hours) into the hypophyseal portal blood. GnRH release is stimulated by kisspeptin neurons and influenced by nutrition (leptin), stress and light.
2. Anterior pituitary: Gonadotroph cells respond to GnRH by releasing LH (luteinising hormone; in males also called ICSH – interstitial cell stimulating hormone) and FSH (follicle-stimulating hormone).
3. Testes: LH acts on Leydig cells → testosterone. FSH acts on Sertoli cells → supports spermatogenesis, ABP and inhibin production. Testosterone (bound to ABP) acts on Sertoli cells too.

Regulation by negative feedback:

1. Testosterone (and oestradiol formed from it by aromatase) inhibits GnRH secretion from the hypothalamus and LH secretion from the pituitary.
2. Inhibin B from Sertoli cells selectively inhibits FSH secretion.
3. Thus hormone levels stay steady. Pulsatile GnRH is essential: continuous GnRH (e.g. long-acting GnRH analogue drugs) desensitises the pituitary and stops LH/FSH – used to treat prostate cancer.

Role of Reproductive Hormones

Other hormones involved: dihydrotestosterone (DHT) for external genitalia and prostate; anti-Müllerian hormone from foetal Sertoli cells, which causes regression of female (Müllerian) ducts; prolactin, oxytocin (sperm transport), thyroid hormones and insulin play supporting roles.

Mechanism of Action of Androgens

Androgens are steroid (lipid-soluble) hormones, so they act through intracellular receptors and change gene expression (genomic action).

1. Transport: In blood, most testosterone is bound to sex hormone-binding globulin (SHBG) and albumin; only free testosterone (about 2%) is active.
2. Entry: Free testosterone diffuses through the plasma membrane.
3. Conversion: In target tissues like the prostate, skin and hair follicles, the enzyme 5α-reductase converts it into the more potent DHT; in some tissues (brain, bone, fat) aromatase converts it to oestradiol.
4. Receptor binding: The hormone binds the androgen receptor (AR) in the cytoplasm; heat-shock proteins attached to the receptor are released.
5. Dimerisation and nuclear entry: Hormone–receptor complexes pair up and move into the nucleus.
6. DNA binding: The complex binds specific DNA sequences called androgen response elements (AREs) in target genes, with co-activator proteins.
7. Transcription and translation: mRNA is produced and new proteins are made (e.g. structural proteins, enzymes, PSA), producing the androgenic effect. This takes hours.
8. Non-genomic actions: Rapid effects (seconds–minutes) through membrane receptors and Ca²⁺ signalling.

Clinical examples: Mutations in the AR gene cause androgen insensitivity syndrome (XY individuals with female external appearance); 5α-reductase deficiency causes ambiguous genitalia; 5α-reductase inhibitors (finasteride) are used for enlarged prostate.

Puberty and Aging in Males

Puberty is the period when the reproductive system matures and the individual becomes capable of reproduction. In boys it usually begins between about 9 and 14 years.

Hormonal changes:

1. During childhood GnRH secretion is suppressed. At puberty kisspeptin signalling increases and GnRH pulses restart, first at night during sleep.
2. LH and FSH rise → testes enlarge → testosterone rises sharply; growth hormone and IGF-1 also rise.
3. Body fat signal (leptin) and general health influence the timing.

Physiological changes (described by Tanner stages): enlargement of testes (first sign), growth of penis and scrotum, pubic, axillary and facial hair, deepening of voice (larynx enlarges – "Adam's apple"), growth spurt and increase in muscle and bone mass, broad shoulders, oily skin and acne, start of sperm production (spermarche) and nocturnal emissions, development of libido, and closure of growth plates later by oestrogen.

Aging in males: Unlike menopause in women, men have no sudden stop; changes are gradual (sometimes called andropause or late-onset hypogonadism).

1. Testosterone falls slowly (roughly 1% per year after middle age), while SHBG rises, so free testosterone falls more; LH and FSH may rise.
2. Fewer Leydig and Sertoli cells; lower sperm count, motility and normal forms; semen volume decreases; more DNA damage and new mutations in sperm with increasing paternal age.
3. Effects: decreased libido and erectile function, loss of muscle and bone (osteoporosis), increased fat, fatigue, mood changes.
4. Benign prostatic hyperplasia (BPH) – enlarged prostate causing urinary difficulty – and prostate cancer become common.
5. Many men remain fertile into old age, though fertility declines.

Likely exam questions

1. (Long, 8 marks) Explain the organisation and feedback regulation of the hypothalamic–pituitary–gonadal axis in males.
2. (Long, 8 marks) Describe the mechanism of action of androgens at the cellular level.
3. (Short, 4 marks) Write the functions of FSH and LH in the male.
4. (Short, 4 marks) Write a note on inhibin.
5. (Short, 4 marks) Describe the hormonal and physiological changes during puberty in males.