Human Reproduction, Development and Ageing - Week 3 Lecture Notes

Topic = Male Reproductive System

Reproductive System Overview
  • Core function of BOTH sexes: production of viable gametes and successful offspring formation.

    • Male: create and deliver sperm to female tract for fertilisation.

    • Female (from previous lecture): produce ovum and provide protected site for fertilisation, implantation and embryonic development.

  • Lecture 3 focus: Male anatomy, physiology, hormone regulation, spermatogenesis, clinical disorders, and upcoming Literature Review Plan.

Male Hormone Regulation – General Principles
  • Governed by Hypothalamus–Anterior Lobe of Pituitary (ALP)–Testes axis.

    • Interaction of positive & negative feedback loops keeps testosterone within a narrow range until late life.

    • Environmental inputs (light, stress, temperature, pheromones) affect axis via the brain; stress has measurable inhibitory effects.

  • Key hormones & pulsatility:

    • GnRH released in pulses every 1–3 h; continuous exposure desensitises receptors.

    • LH → Leydig cells → testosterone.

    • FSH → Sertoli cells → spermatogenesis support & inhibin.

    • Inhibin: Sertoli-derived; specifically suppresses FSH release.

  • Broad summary loop:

    1. Hypothalamus releases GnRH.

    2. GnRH → ALP → LH & FSH.

    3. FSH promotes spermatogenesis (with testosterone).

    4. LH stimulates Leydig cells to secrete testosterone.

    5. Rising testosterone ⇒ male sexual maturation, libido, negative feedback on GnRH/FSH/LH (with inhibin).

Male Reproductive Anatomy

• Main structures: scrotum, testes, epididymis, vas deferens, ejaculatory ducts, urethra, penis, accessory glands (seminal vesicles, prostate, bulbourethral).

Scrotum
  • Pouch holding testes outside abdominopelvic cavity; needed because optimal spermatogenesis temperature ≈ 34^{\circ}\text{C} (≈ 3^{\circ}\text{C} below core 37^{\circ}\text{C}).

  • Pampiniform venous plexus acts as counter-current heat exchanger; scrotum contracts/relaxes in response to temperature, altering surface area.

  • Contains spermatic cords (vas deferens, nerves, blood & lymph vessels); traverses inguinal canal.

    • Weakness → inguinal hernia: bowel/omentum protrusion; common in males due to canal.

Testes
  • Plum-sized (≈4 cm × 2.5 cm).

  • Covered by two tunics:

    • Tunica vaginalis (peritoneal-derived, superficial).

    • Tunica albuginea (fibrous; septa divide testis into ≈250 lobules).

  • Each lobule houses 1–4 seminiferous tubules (site of sperm production).

  • Embryology & descent:

    • Develop high in abdomen; descend through inguinal canal into scrotum between 7 mo gestation and birth.

    • Failure → cryptorchidism: undescended testes; ↑ risk infertility & malignancy.

Comparative Size & Mating Implications
  • Testes mass correlates with body mass and mating system:

    • Large testes in multi-male (polyandrous) species (e.g., chimpanzee) for sperm competition.

    • Smallest in single-male (monogamous) species.

    • Humans intermediate; suggests mild/moderate polygyny historically.

Seminiferous Tubules – Histology & Cells
  • Surrounded by 3–5 layers of contractile myoid cells.

  • Sertoli (nurse) cells:

    • Form blood-testis barrier (BTB) via tight junctions (physical, immunological & physiologic).

    • Feed developing germ cells (lactate instead of glucose); secrete androgen-binding protein (ABP), fluid for sperm transport, inhibin.

    • Concentrate testosterone locally.

  • Spermatogenic cells: successive stages from spermatogonia → spermatids.

  • Leydig (interstitial) cells in interstitium produce testosterone under LH.

Penis
  • Copulatory organ delivering semen.

  • Parts: root, shaft, glans (distal expansion), prepuce/foreskin (may be removed by circumcision).

  • Erectile tissues (vascular sinusoids within CT & smooth muscle):

    • Corpora cavernosa (paired dorsal columns).

    • Corpus spongiosum (ventral; surrounds spongy urethra; expands to glans).

Duct System
  • Epididymis (head, body, tail):

    • Sperm storage/maturation (~20 days transit); tail stores until ejaculation.

  • Vas (ductus) deferens:

    • Continuation from tail; ascends in spermatic cord → inguinal canal → pelvic cavity.

    • Distal dilation = ampulla; joins seminal vesicle duct → ejaculatory duct → prostatic urethra.

    • Vasectomy: cutting/ligating vas; sperm still produced but not ejaculated (form of contraception).

Accessory Glands & Semen Composition
  • Seminal vesicles (≈60 % semen): alkaline, fructose (ATP fuel), prostaglandins (↓ cervical mucus viscosity, ↑ uterine contractions).

  • Prostate (≈30 %): slightly acidic, enzymes for sperm activation (e.g., PSA, fibrinolysin).

    • Pathologies: Benign prostatic hyperplasia (BPH) (urethral compression); prostate cancer (2nd leading male cancer death after lung).

  • Bulbourethral (Cowper) glands (<5 %): clear mucus for urethral lubrication & neutralisation of residual acidic urine.

  • Semen overall:

    • Volume per ejaculation: 2–5\,\text{mL}; only ≈10 % cellular sperm.

    • Sperm density: 20–150\times10^{6}\,\text{mL}^{-1} (WHO: normal ≥15\times10^{6}; oligospermia below).

    • pH 7.3–7.5 (alkalinity counteracts vaginal acidity).

    • Of ≈375\times10^{6} sperm/ejaculate, only ~200 reach the oocyte.

Spermatogenesis & Spermiogenesis
  • Begins at puberty (~age 14) and continues life-long; average production ≈4\times10^{8} sperm day⁻¹.

  • Phases within seminiferous tubules:

    1. Mitosis of spermatogonia (stem cells): each division yields Type A (basal lamina renewer) & Type B (primary spermatocyte) daughter cells.

    2. Meiosis I: primary spermatocyte → two secondary spermatocytes (haploid).

    3. Meiosis II: secondary spermatocytes → four early spermatids.

    4. Spermiogenesis: metamorphic phase; spermatids → spermatozoa.

    • Nuclear condensation, acrosome formation (from Golgi; digestive enzymes for zona pellucida penetration), mitochondrial sheath in midpiece (ATP for motility), flagellum formation, excess cytoplasm shed.

  • One primary spermatocyte yields four genetically unique sperm.

Sertoli Cell Functions – Expanded Significance
  • Nutrient/metabolite provision (lactate, ions, ABP).

  • Immunoprotection (BTB prevents autoimmune response to late germ cells).

  • Paracrine signalling for germ cell differentiation.

  • Mechanical support & phagocytosis of residual cytoplasm.

  • Secretion of inhibin & Müllerian-inhibiting substance (AMH) in fetal testes.

Endocrine Axis – Detailed Map & Feedback Loops
  • GnRH pulsatile → anterior pituitary.

  • LH binds Leydig cell receptors (cAMP pathway) → testosterone secretion.

  • FSH binds Sertoli cells (cAMP) → ABP ↑ testosterone local concentration, stimulates spermatogenic support.

  • Testosterone & inhibin exert negative feedback:

    • Testosterone on hypothalamus (↓ GnRH) & pituitary (↓ LH).

    • Inhibin specifically on pituitary (↓ FSH).

  • Developmental hormone timeline (graph):

    • High Leydig activity fetal weeks 11–20 (genital differentiation).

    • Quiescence post-birth until “mini-puberty” (months 1–6) and true puberty.

Semen Analysis & Clinical Relevance
  • Volume: 3–5\,\text{mL}; evaluate viscosity, liquefaction time.

  • Concentration: normal mean 75\times10^{6}\,\text{mL}^{-1}; WHO lower reference 15\times10^{6}.

  • Motility: ≥40 % progressive within 60 min.

  • Morphology: ≥4 % normal forms (strict Kruger); <20 % abnormal of normals.

  • Only ~0.00005 % of sperm reach oocyte → underscores quality > quantity in fertilisation.

Male Reproductive Disorders (Selected)
  • Benign prostatic hyperplasia (BPH): almost universal in ageing men; obstructive LUTS, weak stream, nocturia.

  • Prostate cancer: PSA screening; metastasises to bone; 2nd most common male cancer death.

  • Cryptorchidism: undescended testis; ↑ infertility & testicular cancer risk.

  • Inguinal hernia: protrusion via inguinal canal; surgical repair.

  • Testicular torsion: twisting of spermatic cord; acute ischemia.

  • Epididymitis: infection/inflammation; often STI-related in young men.

  • Hypogonadism/Low testosterone: ↓ libido, infertility, metabolic effects; may require TRT.

  • Erectile dysfunction: vascular, neurogenic, endocrine or psychogenic.

  • Phimosis: tight foreskin; may impede hygiene/sexual function.

  • Infertility/Sterility: multifactorial – hormonal, genetic (e.g., Y-microdeletions), obstructive, varicocele.

Ethical, Philosophical & Practical Implications
  • Managing male fertility (vasectomy, ART) raises issues of consent, reversibility, societal norms.

  • Screening (PSA) debates: balance early detection vs overdiagnosis.

  • Use of testosterone supplementation: performance vs therapy; potential abuse.

  • Cryptorchidism surgery timing to preserve fertility—guideline evolution.

Literature Review Plan (Assessment Guidance)
  • Conducted Week 4 lab session.

  • Bring: Reference document, LRP template, preliminary research notes.

  • Provided: Topic allocation list, guidance material.

  • Expected deliverables:

    • Identify scope of allocated topic.

    • List 3–4 key findings, gaps, theories, or studies discovered so far.

    • Explain how these link to the critical elements/questions of your review.

    • Prepare to discuss methodology and relevance to human reproduction.

Connections to Previous & Future Lectures
  • Builds on Lecture 1 (Meiosis & Gametogenesis) – understanding meiosis crucial for spermatogenesis stages.

  • Precedes Fertilisation & Pregnancy lecture; sperm transport, capacitation, acrosome reaction will be revisited.

  • Endocrinology principles will parallel female cycle (contrast cyclic vs constant hormone patterns).

Real-World & Clinical Correlations
  • Knowledge underpins contraceptive strategies (vasectomy, hormonal suppression).

  • Assisted Reproductive Technology (ART) relies on semen analysis, sperm preparation, and endocrine manipulation (later lecture).

  • Understanding temperature sensitivity of spermatogenesis influences lifestyle advice (tight clothing, hot baths, laptop on lap, varicoceles).

  • Environmental disruptors (phthalates, heat) act via endocrine axis – public health considerations.