PHYSIOLOGY OF THE MALE REPRODUCTIVE SYSTEM Physiology of the Male Reproductive System Harvard-MIT Division of Health Sciences and TechnologyHST.071: Human Reproductive BiologyPHYSIOLOGY OF MALE REPRODUCTION Proper understanding of male reproductive physiology and related pathology requires appreciation of the anatomy and development of the male genital and ductal system, physiology of the testis, hormonal control oi the testis, as well as the processes involved in deposition of the seminal fluid within the female genital tract. Anatomy The male genital tract is depicted below, and has several main components. In essence, the testis produces sperm, which pass through a series of ducts and are finally expelled via the urethra together with seminal plasma produced by the accessory sexual organs. The testis The testis descends from a retroperitoneal position through the inguinal canal to take its place in the scrotum during the eighth fetal month. Reasons for its unusually vulnerable position are uncertain, but may well be due to the lower temperature required for spermatogenesis. A countercurrent vascular heat exchange system is present to promote cooler temperatures. Seminiferous tubules comprise 95% of testicular volume, and are devoted to the production of spermatozoa. Each tubule is 30-70 cm long and 200-300 um in diameter. There are approximately 500 tubules per testis. The tubules are divided by fibrous septae, and surrounded by the tough tunica albuginea. Interstitial tissue located between the seminiferous tubules is comprised of connective tissue, blood vessels, lymphatics, and Leydig cells which produce testosterone. Sperm produced by the seminiferous tubules pass out of the testis into the ductal system, beginning with the rete testis and on into the epididymis. The epididymis is a single convoluted duct approximately 20m long, and is divided into caput (head), corpus (body), and cauda (tail), which then continues as the vas deferens. Sperm in the vas deferens is joined by seminal vesicle secretions as they pass through the prostate via the ejaculatory ducts into the urethra. DEVELOPMENT The gonad at eight weeks is undifferentiated, but under the influence of the Y chromosome a complex series of events occur which result in development of the male reproductive system. Testosterone production causes maturation of the Wolffian ducts into the male genital duct system (epididymis, vas, seminal vesicles). At the same time, testicular production of Mullerian Inhibiting Substance (MIS) causes degeneration of the Mullerian ducts, which in the female Physiology of the Male Reproductive Systemform the uterus and Fallopian tubes. Conversion of testosterone into dihydrotestosterone by the enzyme 5 alpha reductase causes masculinization of the external genital system such as the scrotum and penis. Testicular Function The testes have two main functions in the adult, and an additional one in the developing fetus. In the adult, the testis acts as an exocrine organ, with the production and secretion of sperm. It also acts as an endocrine organ by its production and secretion of testosterone into the blood. The additional fetal function has already been noted, namely the secretion of MIS to cause regression of female structures. Sperm production occurs within the seminiferous tubules, and is the result of complex local events as well as distant regulatory signals. Under the control of local testosterone production by the Leydig cells, the Sertoli cells within the seminiferous tubules provide an appropriate environment for the development of immature germ cells into mature spermatozoa. Sertoli cells The seminiferous tubules are comprised entirely of Sertoli cells and germ cells. Sertoli cells are tall columnar cells with numerous branches which envelop all the differentiating germ cells from basement membrane to the tubule lumen. Tight junctions between Sertoli cells create a blood-testis barrier, and separate the germinal epithelium into basal and adluminal compartments. Only the most immature germ cells are present in the basal compartment, with more advanced germ cells enjoying a specialized micro-environment within the adluminal compartment. A single Sertoli cell may envelop 10-20 developing germ cells. Sertoli cell functions include: support and nutrition of germ cells; release of mature germ cells into the lumen; translocation of developing germ cells in an adluminal direction; secretion of androgen binding protein, transferrin, inhibin; cell-cell communication via gap junctions to coordinate spermatogenesis; blood-testis barrier. Physiology of the Male Reproductive SystemGerm Cells Germ cells begin as spermatogonia, which are the stem cells lining the basementlayer of the seminiferous tubule. They are small, rounded, mitotically active cells which are sensitive to chemotherapy or radiation. Type A spermatogonia develop into Type B spermatogonia, which subsequently become primary spermatocytes during the first meiotic prophase. Primary spermatocytes go through a series of stages (preleptotene, leptotene, zygotene, pachytene, diplotene) which are identified on the basis of cellular size and increasing nuclear condensation. Secondary spermatocytes result from the first reduction division. They are diploid, in contrast to the primary spermatocytes which are tetraploid. The second meiotic prophase is very short (1 day) so secondary spermatocytes are not readily visible in tissue sections. Spermatids result from the second reduction division and are therefore haploid. They are numerous, and are found near the tubule lumen. Spermatids may be in many stages of differentiation, but cells in any one cluster are always synchronized. Spermatozoa The morphologically mature spermatozoon is released into the tubule lumen. It is a highly polarized cell, approximately 60um long in the human. The head consists of the condensed nucleus, the acrosome, and associated membrane structures. The tail consists of a neck, middle piece containing a sheath of mitochondria, the principal piece, and an end piece. A "9+2" axoneme extends from the neck to the end piece. The entire tail is covered by the plasma membrane. See Infertility in the Male. p. 108, Lipshultz, L. I. & Howards, S. S. (eds). Churchill Livingstone, Edinburgh. Leydig Cells Leydig cells lie in the testicular interstitium between the seminiferous tubules, and seem primarily involved in the production of testosterone for