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Dr Mubeen Goolam Department of Human Biology Email: mubeen.goolam@uct.ac.za

Functional Histology of the Male Reproductive System and Reproductive Endocrinology

Certain slides courtesy of A/Prof Liz van der Merwe

Critical Resources for a full understanding of this section Kierszenbaum  - Histology and Cell Biology: An Introduction to Pathology– Chapter 20 Spermatogenesis Previous and current lectures on Male Reproductive System (there will be some overlap)

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Brain / Hypothalamus
Test
GnRH
FSH + LH
terone
Testis
Pituitary
Vas deferens
,v—• Epididymis
Sertoli
ælls
Leydig —y
erone
cells

Reproductive Capability: Dependent on integrated relationship between Hypothalamus Anterior pituitary Reproductive organs Target cells of sex hormones Neural & hormonal signaling, feedback

Full size image for 'The Male and Female Reproductive Systems'

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Functions of the Male Reproductive Tract   Overall aim: to propagate species What is required? Production of spermatozoa Conveying spermatozoa from testis to female reproductive tract Maturation of spermatozoa (in epididymis) -  takes 30 days Storage (in epididymis and vas deferens - can be for several months). Emission: emptying contents into prostatic urethra Production of seminal, prostatic secretions & mixing with spermatozoa & fluid - semen.  Erection & ejaculation.

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Components of the Male Reproductive Tract

Modified from  Stevens & Lowe: Human histology 2 nd  ed

Colour code:  Exocrine glands,   Excretory ducts,  Testis

Scrotum Venous  Pampiniform  plexus Cremaster  muscle

Prostate Bulbourethral Gland Seminal vesicle

Epididymis Ejaculatory duct Urethra  Vas Deferens

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Diagram

Description automatically generated

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Not visible - supporting framework, septum

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‘Seminiferous epithelium’ in  Kierszenbaum

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Ross & Romrell Histology: Text & Atlas 2nd Ed Peritubular cells (myoid)  Tight Junctional  Complex Basement membrane  Sertoli cells  Spermatogenic cells

spermatogonia spermatocytes spermatozoa spermatids

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Seminiferous tubule:  Sertoli cells – Structure/function

Tall columnar – deep cytoplasmic  infoldings   Support, protect, nourish developing  		 spermatogenic  cells Phagocytosis of excess cell portions  		(residual bodies)  Facilitate release of spermatozoa ( spermiation ) NB! Forms  blood-testis barrier : (immunological privilege)  NB: Tight junctions  	 secrete FAS ligand – eliminates T cell mediated immune response

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Mechanism of Maintaining the Blood-Testis Barrier:

Basal compartment Spermatogonia   Early 1 °  spermatocyte

New  Tight junction forms under Early 1 °  spermatocyte

Adluminal  compartment Meiotic 1 °  spermatocyte 2 °  spermatocytes Spermatids Spermatozoa

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Ross & Romrell: Histology: Text & Atlas 2nd Ed

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1.   Spermatocytogenesis Spermatogonia  to  1 ⁰  spermatocytes Mitosis

Basal compartment:     Type A & B spermatogonia ( diploid ) Type Ad   =  dark  nucleus - “stem” cells Type Ap   =    pale nucleus  - undergo several  mitotic divisions Type B  = nuclei show chromatin  	condensed into clumps.

Ross & Romrell Histology: Text & Atlas 2nd Ed

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2. Spermatocyte phase Meiosis I & II  1 Spermatocyte to 4 spermatids

Adluminal  compartment:   Primary spermatocytes -  Meiosis I Secondary spermatocytes -  Meiosis II Spermatids – Post-meiosis cell

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Diagram

Description automatically generated with low confidence

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Adluminal compartment:   Spermatids  (4)   =haploid   Developmental phases Golgi  Cap  Acrosomal Maturation Spermatozoa

3. Spermiogenesis Spermatids to spermatozoa Cell differentiation/maturation of haploid gametes

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Enzymes from Golgi form  acrosomal vesicle  .

Full size image for 'The Male Reproductive System'

White -  Endocrine and Reproductive Physiology, Fifth Edition

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Acrosome “caps” nucleus Centrioles migrate to opposite pole to vesicle.   Axoneme starts to form Spermatid rotates - acrosome points towards wall of seminiferous tubule

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Acrosomal phase Increases coverage Axoneme develops - flagellum Manchette forms Mitochondria migrate Nucleus condenses Maturation phase  Shedding of cytoplasm  Spermatozoa formed  Cytoplasm phagocytosed  Manchette disassembles

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Large polygonal cells near  capillaries  Typical features of  Steroid producing cells     L arge  pale vesicular nuclei  Granular  eosinophilc  cytoplasm filled with oxidative enzymes,  esterases   &  steroid dehydrogenases   Cells also found in mediastinum & spermatic cord.  Produce  testosterone  - acts on spermatogenic,  sertoli  cells & and distant target cells.

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Cancer chemotherapy: (Transient  aspermatogenic ) Affects Spermatocytes mitotic & meiotic Does not affect: Sertoli cells – they are post mitotic (post puberty) Spermatogonia- “dormant” stem cells

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Epididymis Ejaculatory duct  Vas Deferens

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Rete testis:  Low cuboidal epithelium with single cilium

Efferent  ductules :  Mixed low cuboidal epithelium (with microvilli) & tall ciliated columnar epithelium

Epididymis:  Tall pseudostratified columnar epithelium with giant microvilli ( stereocilia )

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Histology Columnar pseudostratified epithelium Tall columnar cells  – giant microvilli (stereocilia) for absorption Basal cells  - regenerative Apical cells , clear cells, intraepithelial lymphocytes – difficult to spot due to being clear Functions Requires testosterone to function  Secretory  – selected amino acids, sialic acid, glycoproteins  Peristaltic movements  – move spermatozoa along tubule Spermatozoa  “gain” forward motility – in tail region Involved in maturation of sperm

Epididymis: head (caput), body (corpus) tail (cauda)

Full size image for 'Male Reproductive System'

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Stereociliated  pseudostratified columnar epithelium During a vasectomy  the vas deferens is the structure that is cut and tied or sealed

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Prostate Largest accessory gland, pierced by the urethra and ejaculatory ducts 30 to 50 individual compound  tubuloacinar  glands

highly coiled tubular structures about 15 cm long.  Outgrowth of vas deferens The lumen is lined by a pseudostratified columnar epithelium composed of short basal cells and low columnar cells Inner circular & outer longitudinal smooth muscle

Bulbourethral glands Compound  tubuloacinar  glands  Simple secretory epithelium simple cuboidal or simple columnar  .

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Seminal vesicle  (60% of semen) Secretions:  Fructose - energy Prostaglandins -  stimulates tubular muscular contractions  Fibrinogen  - coagulation of semen   Prostate  (approx. 30% of semen) Secretions:  Proteolytic enzymes,  Prostatic specific acid phosphatase, prostate specific antigen, fibrinolysin Major function of  liquefying coagulated semen after deposition in the female genital tract. Bulbourethral glands  Secretions: Galactose  Sialic acid. Lubricating function

Semen:   secretions from the accessory glands and 200 to 400 million spermatozoa

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Prostate   (30-50 compound tubuloacinar glands)

Modified from  Stevens & Lowe: Human histology

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Prostatic epithelium changes relate to its activity

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Scrotum Venous Pampiniform plexus Cremaster muscle

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Erectile tissue found in corpus spongiosum and corpora cavernosa

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Deep dorsal vein
Dorsal arteries
Dorsal nerves
(somatic)
Deep dorsal vein
Tunica albuginea
Sinusoidal spaces
Corpora cavernosa
Cavernous artery
Prostate
Circumflex
artery
Circumflex Sinusoidal
Cavernous nerve
(autonomic)
Dorsal artery Dorsal nerve
(somatic)
Erect
D)
vein
spaces
Flaccid
Helicine arteries
Trabecular smooth
muscle
Subtunical venular
plexus

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Sensory:  Glans penis (sensory end organ)  - (pudendal – sacral plexus- sacral spinal cord to CNS) – sexual sensation Sensory input from:  scrotum, perineal structures, anal epithelium. Internal structures – bladder, urethra, prostate, seminal vesicles, testis, vas deferens  – filling with secretions Mild infections cause inflammation – which can result in continuous sexual desire “aphrodisiac” drugs are bladder epithelium irritants  Also induced by mental stimulation Integration in spinal cord: Inherent reflex – sacral-lumbar spinal cord or psychic  - usually both.

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Autonomic: - penile response Parasympathetic : Via sacral spinal cord through –  pelvic nerve  - pelvic plexus – cavernous nerve in penis  - release Nitric oxide (NO)/ Vasoactive intestinal peptide (VIP) and Acetylcholine (ACH) cause  dilation of spiral arteries Sympathetic  – via lumbar spine – sympathetic chain - splanchnic nerve -–  Hypogastric – pelvic plexus – Cavernous nerves Decrease noradrenaline  –  loss of sympathetic tone Somatic: ejaculation response Afferent (sensory) – Efferent (motor)  motor branch  of  pudendal nerve  – secretes non-cholinergic transmitters & NO - striated muscle ( bulbospongiousus  increases  engorgment ) and smooth muscle around tract cause contractions results  in ejaculation Afferent innervation: Dorsal nerve   - main terminus of pudendal – main tactile  sensory input

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Erection flaccid to hardened penis –engorgement of erectile tissue  parasympathetically  induced vasodilation of penile arterioles &  Loss of   sympathetic  tone to muscular stroma Lubrication Secretion of mucus from bulbourethral and urethral glands   parasympathetically  induced increased secretion of mucus Emission emptying sperm, accessory gland secretions into urethra sympathetically  induced contraction of walls of ducts and accessory glands Expulsion (ejaculation)  forceful expulsion of semen from penis Somatic (motor neuron)  induced contraction of skeletal muscles at base of penis

Physiology of erectile response and ejaculation

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Hypothalamus  GnRH/LHRH Anterior pituitary LH, FSH Leydig Cells Testosterone –  DHT Sertoli Cells ABP Inhibin  Activin

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Seminiferous tubule:  Sertoli cells: Physiology

Secretory Functions & Hormone regulation: Express  testosterone & FSH receptors  Secrete fluid (ions & proteins into lumen)  Produce & secrete  ABP  – exocrine 	-Into lumen of the tubule (concentrates 	local testosterone)  Produce & secrete  antimullerian  hormone  	-  During embryogenesis - suppresses 	the formation of the  mullerian  duct  Produce & secrete  inhibin 	- inhibits the release of FSH by the 	anterior pituitary Produce & secrete  activin  	- facilitates the release of FSH from the 	anterior pituitary

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Cryptorchidism (undescended testis)  Congenital & acquired ductal obstruction in reproductive tract Immotile cilia (Kartagener’s syndrome) Sertoli cell only syndrome (no germ cells)  Klinefelter’s syndrome – 46XXY – low testosterone high  oestradiol Vasectomy  -an elective procedure Chemotherapy can cause transient infertility 	affects  meiotic & mitotic  spermatogenic  cells 	does not affect Sertoli cells (post mitotic)  	less effect on slow cycling spermatogonia

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Spermatogenesis can only occur at 34-35°C. In undescended testis, all germ cells are eventually killed. Only  sertoli  cells remain – hence infertility.

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