Life in the womb: fetal determinants of male reproductive health.

CHEMES HE

Houston, Texas.

Congreso; 35 Meeting. American Society of Andrology; 2010

American Society of Andrology

Relevance of Human Testis Feto Neonatal development for future fertility. Hector E. Chemes, MD, PhD. Center for Research in Endocrinology, National Research Council and Buenos Aires Children´s Hospital. Argentina. In most laboratory animals there is continuity between neonatal activation of the testis and the beginning of puberty. This is quite different in high primates and humans because a long period of infancy separates both events. This period has been considered a quiescent phase of testicular development since only spermatogonia are seen among immature Sertoli cells (SC) and no Leydig cells are present in the interstitium. Yet, during infancy there is inapparent but vigorous testicular activity that needs to be successfully completed to fulfill the potential for pubertal development and normal fertility. In contrast with high spermatogenic yields in rodents, early pubertal spermatogenesis in humans shows considerable germ cell (GC) degeneration that delays spermatogenic completion until late puberty. This is the reason for the long duration of puberty in primates. In the immature rat, complete spermatogenesis is achieved in the duration of 1 spermatogenic cycle (45-50 days), while 15-20 cycles (3-4 years) are needed in humans. During fetal life and infancy immature SC proliferate, thus increasing the potential for future GC expansion since each SC can lodge a limited number of GC. Immature SC display functions like aromatase activity, estrogen and AMH secretion or maximal FSH responsiveness that indicate a kind of differentiation quite diverse from that of the mature state. An example of this is the absent or limited expression of SC androgen receptors. In view of high neonatal levels of testosterone, this physiologic androgen insensitivity keeps SC immature and prevents precocious spermatogenesis. During this presentation, the physiopathology of various developmentally-related testicular disorders will be discussed: 1) Hypogonadotrophic hypogonadism or endocrine disruptors may compromise SC proliferation. Testicular mitotic activity in the neonatal rat is critically dependent on FSH. This requirement is also likely to exist in humans, hence recent trials of neonatal treatment with FSH when Hypogonadotrophic Hypogonadism is suspected. 2) In testicular dysgenesis there is failed GC maturation and persistence of embryonic gonocytes with possible transformation to intratubular GC neoplasia that may evolve to GC cancer in adulthood. 3) The diminution of GC numbers during infancy in chryptorchidism is probably primary or dysgenetic in nature and not, as previously believed, a consequence of GC degeneration from early infancy due to the non-scrotal testicular position.