HISTOLOGY FULL-TEXT

William A Beresford MA, D Phil ©
Professor of Anatomy
Anatomy Department, West Virginia University, Morgantown, USA

Chapter 28 MALE REPRODUCTIVE SYSTEM

Male reproductive organs form spermatozoa, suspend them in secretions produced by accessory glands, and conduct them, via seminal pathways, to the female reproductive tract by mating behaviour. These activities are influenced by hormones, including ones formed by the testes. Powerpoint

A TESTIS

l General morphology
l Very dense CT capsule - tunica albuginea, with an outer mesothelium-covered visceral tunica vaginalis propria.
2 Septa/septula extend from the capsule to the CT mediastinum.
3 In the partitions thus formed (lobuli testis), lie looped, coiled seminiferous tubules, lined by germinal epithelium, and feeding via straight
4 tubuli recti into cuboidal epithelium-lined ducts of the
5 rete testis, which lead through the mediastinum to roughly 6-l2
6 ductuli efferentes. These take the spermatozoa to a
7 single, coiled, tubular epididymis lying behind the testis.
8 Between, and outside, the coils of a seminiferous tubule lie blood and lymph capillaries, cells and fibres of CT, and hormone-secreting Leydig interstitial cells.
9 The testis is a mixed endocrine and compound, tubular, cytogenic exocrine gland.

2 Seminiferous tubule and spermatogenesis
l The tubule has a substantial support of the basal lamina, plus two or more alternating layers of collagen fibres and muscle-like/myoid cells, with adherent external lamina.
2 The stratified germinal epithelium has cells of two kinds:

(a) spermatogenic cells, quiescent or in the various phases of development;
(b) Sertoli supporting cells; well attached, tall with an irregular columnar form, and a pale ovoid nucleus with a prominent nucleolus; taking up testosterone; and controlling spermatogenesis.

3 Spermatogenesis in the epithelium is initiated by the pituitary hormone FSH, and passes through these stages:

(a) spermatogonium, spheroid cell lying basally, divides mitotically for several generations, then become a
(b) primary spermatocyte, larger, divides by the first meiotic division (to halve the chromosome number to haploid 23 and introduce genetic variety), to produce
(c) secondary spermatocytes, small, soon undergoing the second meiotic division, maintaining the chromosome number at 23, to give
(d) spermatids, smaller and incompletely separated, which, without dividing, metamorphose by the process - spermiogenesis - into
(e) spermatozoa, released into the tubule's lumen.

The stages are not all seen at any one place in the germinal epithelium; various combinations exist and are distributed as a mosaic in the tubule's wall.

4 Spermatogenesis is vulnerable to heat, X-rays, dietary deficiencies, pesticides, and other poisons. Conventional microscopy reveals defects in sperm shape and motility, leading to infertility. FISH and other molecular techniques are needed to assess genetic damage, sometimes arising during meiosis.
Spermatogenesis is protected to a degree by the tight attachments between the capillary endothelial cells and, separately, between the Sertoli cells, creating a two-tiered blood-testis barrier, for example, against immune attack. The inner protected compartment of the seminiferous tubule is the 'adluminal' compartment.

5 The spermatozoon is a very elongated motile cell, with a cell membrane enclosing the:

(a) acrosomal head cap, with an enzyme - proacrosin - to aid binding to, and penetration of, the zona pellucida of the oocyte;
(b) nucleus, streamlined in shape, with dense chromatin;
(c) neck joining the head (nucleus and head cap) to the flagellar tail, which has the:
- (i) middle piece, with an axial axonemal core of microtubules in a cilium-like array, nine dense longitudinal fibres and, outermost, a sheath of mitochondria ending at the annulus;
- (ii) principal piece, with both longitudinal and circumferential fibres around the axoneme;
- (iii) end piece, with microtubules like a cilium, but no dense fibres.

6 Spermiogenesis - whereby the spermatid, a typical cell (except for its chromosomes) becomes a spermatozoon - involves:

(a) construction of the acrosome by the Golgi complex;
(b) the nucleus, thus polarized at one end, condenses and elongates;
(c) at the other end, one of the centrioles initiates formation of the flagellar tail;
(d) mitochondria migrate to form a sheath in the tail;
(e) excess cytoplasm is shed as a residual body;
(f) the head of the spermatid throughout spermiogenesis stays held in a recess in a Sertoli cell.

7 Sertoli cell functions: to protect, nourish, and release the spermatids; to phagocytose residual bodies; and to make androgen-binding protein, fluid, and inhibin to influence pituitary FSH release.

3 Endocrine testis
l Leydig cells, eosinophilic, with much smooth ER, lipid droplets, and crystals of Reinke, lie outside the tubules' BLs, constituting a diffuse, steroid-secreting endocrine gland.
2 Leydig interstitial cells are controlled by gonadotrophic interstitial cell-stimulating hormone (ICSH/LH) of the anterior pituitary, and produce the androgenic hormone - testosterone, responsible for:
3 (a) spermatogenesis; (b) development and maintenance of reproductive ducts and accessory glands; (c) secondary sexual characteristics; (d) male mating behaviour; (e) general anabolic effects on metabolism.

B PATHS TRAVERSED BY SPERMATOZOA

l Efferent ducts/Ductuli efferentes
l Unevenly lined by simple, columnar, epithelial cells, in groups of tall ciliated and short secretory; the wall has circular smooth muscle;
2 functions - reabsorption of the fluid used to move sperm out of the testis; maturation of the sperm.

2 Epididymis/ductus epididymidis
l Regularly lined by tall, absorptive, columnar cells with non-motile stereocilia, and smaller basal cells, together forming a pseudostratified epithelium;
2 outside the BL is a little smooth muscle and, between the coils, is a stroma of dense CT with capillaries;
3 functions - as for ductuli efferentes.

3 Ductus deferens/vas deferens
l Lined by an epithelium similar to that of the epididymis, on a lamina propria; in the ampulla, this mucosa has many folds;
2 most of the very thick wall is smooth muscle: inner, longitudinal; middle, circular; outer, longitudinal;
3 adventitia of CT binds it to nerves, blood and lymphatic vessels, and the skeletal cremaster muscle, to comprise the spermatic cord;
4 function - rapid transport of sperm during ejaculation, under sympathetic control.

4 Ejaculatory ducts
l Each occurs after a dilation of the ductus d. - the ampulla;
2 lined by pseudostratified or simple columnar epithelium on CT, without smooth muscle.
3 Ducts open into the prostatic urethra through a hillock on the posterior urethral wall - verumontanum/colliculus seminalis, with its blind recess - utriculus masculinus.

5 Urethra
l Three portions; prostatic, membranous, and cavernous;
2 more details - Chapter 23.B.4

C MALE ACCESSORY GLANDS

l Prostate gland
l Lobulated by septa of CT, with much smooth muscle.
2 Divisible, with histology and rectal-probe ultrasound, into several zones:
.. peripheral (prone to cancer),
.. transitional,
.. central,
.. peri-urethral (subject to benign prostatic hypertrophy), and
.. an anterior non-glandular fibromuscular zone.
3 Large-lumened secretory acini are lined by pale columnar or cuboidal epithelial cells, on a BL. Epithelium is patchily pseudostratified, i.e., bearing some small basal cells.
4 Acini open into many ducts, entering the urethra individually, thus the prostate is a collection of compound tubuloacinar glands.
5 Laminated, rounded, prostatic concretions (originally glycoprotein, but later calcifying) - corpora amylacea - develop in some acini as age increases.
6 Functions - secretion of a watery fluid to dilute the semen; the protease - prostate-specific antigen (PSA) - liquifies the gel from the seminal vesicles to free the sperm; the roles of the citrate (the anionic counterpart to Na⁺) and acid phosphatase are uncertain.
7 PSA serves as a serum marker of prostatic cancer, if excessive for the man's age.
8 The stroma has abundant smooth muscle to make the prostate a self-squeezing gland, without the need for myoepithelial cells. Stroma interacts with the epithelium in the control of growth and secretion, and is a major player in benign prostatic hypertrophy.

2 Seminal vesicles
l Coiled, convoluted, tubular structures; with a
2 very extensively folded mucosa, having
3 a pseudostratified, columnar, secretory epithelium.
4 The wall has circular and longitudinal smooth muscle, and a thin, outer, fibro-elastic adventitia.
5 Functions - secretion of a viscid gel composed of seminogelin, with fructose to provide energy for the sperm, and prostaglandins that may alter contractions in the female tract.

3 Cowper's bulbo-urethral glands
l Compound, tubulo-alveolar gland making special mucus, thought to
2 lubricate and prepare the urethra for ejaculation.

D PENIS

l The thin, elastic skin of the shaft is loosely attached.
2 Connective tissue capsules or tunicae albugineae enclose
3 three roughly cylindrical erectile bodies - two corpora cavernosa penis, and one corpus spongiosum/cavernosum urethrae.
4 The two corpora cavernosa are incompletely separated by a sagittal pectiniform septum. Their endothelium-lined venous sinuses, between a meshwork of dense trabeculae of muscular CT, can be engorged with blood from helicine (coiled) arteries causing erection.

5 Corpus spongiosum

(a) is erectile, but less turgid than the corpora cavernosa;
(b) has less smooth muscle in the CT trabeculae;
(c) originates proximally as the bulbus urethrae and
(d) extends distally to form the bulbous glans, occupied by many veins and nervous receptors, and covered by stratified squamous epithelium, variably keratinized;
(e) ensheaths the cavernous/penile urethra, lined by stratified columnar and finally stratified squamous epithelium.

6 Erection and detumescence are controlled by autonomic nerve fibres to the arteries and trabecular smooth muscle. Erection results from parasympathetically directed trabecular and arterial relaxation, and passive occlusion of the veins draining the corpora.
Sensory nerves serve the glans, skin and deep receptors.
7 Functions - urination/micturition; copulation.

E MALE & FEMALE REPRODUCTIVE DEVELOPMENT

1 The primordial germ cells (prospective gametes) migrate to the gonadal ridges, then a system of dual paired tubules develops, to be either the male or female reproductive tract. Why dual sets of tubules?
2 The para-mesonephric/Müllerian ducts provide the default pathway to turn into female organs.
The mesonephric/Wolffian ducts furnish the driven pathway to a male tubular system.
3 How is the choice made?
The male is male by virtue of the Y chromosome, bearing the SRY gene for the human testis-determining factor (SRY - Sex-determining Region on Y).
The sequelae of the protein expression of SRY are:
.. (i) The indifferent gonad becomes a testis, with Sertoli and Leydig cells. Products of these cells act, gardening-style, as weed-killer and fertilizer.
.. (ii) Sertoli cells make Müllerian-inhibiting factor (MIF), which causes the apoptosis and degeneration of almost all the Müllerian duct (MD).
.. (iii) Leydig cells' testosterone boosts the growth and differentiation of the mesonephric/ Wolffian duct (WD), to make the male tubules - efferent ducts to ejaculatory ducts, and the seminal vesicles.
.. (iv) Testosterone, as 5a-dihydrotestosterone (DHT), also:
(a) converts the urogenital sinus into the male urethra and prostate;
(b) drives the external genitalia into male forms: larger phallus, urethra through the phallus, scrotal halves fused, etc. (The female-male homologues from embryology are needed to understand and correct inter-sex pathologies, seen in the newborn.)
.. (v) In the foetal girl, the Wolffian duct, left without testosterone, withers, while the Müllerian structures continue development.

4 Outcomes of successful sexual development


(OVARY)          UTERINE TUBE           UTERUS        VAGINA      - MD
epoöphoron, paraoöphron                         Gärtner's cyst    - WD


appendix testis                                  prostatic utricle - MD
(TESTIS) EFFERENT DUCTS  EPIDIDYMIS  VAS DEFERENS EJACULATORY DUCT - WD
                                                  SEMINAL VESICLES

In lower case, are the epithelial-lined vestiges of the opposite sex's unneeded duct system. Note that the paradidymis is a remnant of male tubules in the male: surplus efferent ducts.

5 Problems of sexual development can arise at several points, thus:
.. (i) Absent or faulty SRY gene in the male;
.. (ii) Failure of testis cells to respond to the gene's product;
.. (iii) Absent or defective MIF gene; or problems in the MD's response;
.. (iv) Leydig-cell failure to make and deploy the enzymes to produce testosterone;
.. (v) Defective or absent androgen receptor in the Wolffian-duct and external-genital targets for testosterone (J.2)

Meiosis provides an opportunity for such genetic defects to arise.

F MEIOSIS

Ma & Pa meiosis
Aim: from one primary spermatocyte to produce four spermatids, each with:
.. (i) 23 chromosomes (haploid number);
.. (ii) each chromosome derived from either ma or pa - random assortment;
.. (iii) but, with bits of pa's chromosome replacing some of ma's, and vice versa - crossing over.
.. (iv) genetic diversity is the goal, with crossing over (genetic recombination) providing far more diversity than the random assortment of m & p chromosomes
.. (v) Also, think perpendicular quartering cuts for how the cells 'divide' in relation to their chromosomes:

                     ___|___            ___.___
                    |   |   |          |   .   |
                    |   |   |        ------.-------->
                    |___|___|          |___.___|
                        |
                        v

                                                                                                                 m
1º Spermatocyte                                              m                               3-----------------M }
                                         3-----------------M }                             p                     |
3-----------------M       DNA            3-----------------M }    maternal-paternal        {3-----------------M  |
                       ------>                               p     --------------------->  {3*****************P  |
3*****************P     replication      3*****************P }    homologue pairing                              |
                                         3*****************P }                         /     3*****************P }
maternal &                                                                          /
paternal #3 chromosome                   each chromosome now                     /         bivalent for
                                         a pair of chromatids         }       /            crossing-over of
                                         held together by a centromere}    /               aligned chromatids
                                                                        /                  -- for ** 
                                                             DNA excision
                                                             & ligation  
             p                                            <            8 
             { 3---**************M                  <
             { 3-------------****P              <
                                    m       <
               3***----------****M }                                            
               3*****************P }
                                                                                 3***--------------M
                Meiotic division I

   2º spermatocyte           2º spermatocyte                                     3-------------****P

p                                              m     Meiotic division II        
{ 3---**************M     3***----------****M }     --------------------->         4 spermatids
{ 3-------------****P     3*****************P }     centromere splitting
                                                                                 3***----------****M 
                 /          \
                /            \
          random assignment# of maternal                                         3*****************P
          & paternal chromosomes                                                 
          (disjunction), e.g.,

         1 p                   1 m
         2 m                   2 p
         3 p                   3 m
         4 p                   4 m
         5 m                   5 p
         etc                   etc


Sources of trouble . #                                     8
wrong assignment of chromosomes (nondisjunction), e.g.,   |imprecise DNA exchange
2 #21's to one 2º spermatocyte results in one spermatid   |at recombination
having 2 #21's. If, as a sperm, this is the unlucky       |disrupts or cuts out genes
fertilizer, its 2, combined with the 1 from the oocyte,   |
= trisomy 21 in the zygote and eventual child.            |

The Fig. cannot do justice to the intimacy, tight spacing, and connections of synapsis and crossing over, but does convey the outcomes and vulnerabilities. It owes the chromatid recombination pattern, after the reductional and equational divisions, to GS Roeder Genes & Devel 1997;11:2600-2621

William A Beresford, Anatomy Department, School of Medicine, West Virginia University, Morgantown, WV 26506-9128, USA - - e-mail: -- wberesfo@wvu.edu -- wberesfo@hotmail.com -- beresfo@wvnvm.wvnet.edu -- fax: 304-293-8159