Clinical aspects of male germ cell apoptosis during testis development and spermatogenesis

Abstract

Apoptosis appears to have an essential role in the control of germ cell number in testes. During spermatogenesis germ cell deletion has been estimated to result in the loss of up to 75% of the potential number of mature sperm cells. At least three factors seem to determine the onset of apoptosis in male germ cells: (1) lack of hormones, especially gonadotropins and androgens; (2) the specific stage in the spermatogenic cycle; (3) and the developmental stage of the animal. Although male germ cell apoptosis has been well characterized in various animal models, few studies are presently available regarding germ cell apoptosis in the human testis. The first part of this review is focused on germ cell apoptosis in testes of prepubertal boys, with special emphasis on apoptosis in normal and cryptorchid testes. A higher percentage of apoptotic spermatogonia was seen in the cryptorchid testes than in the scrotal testes. The hCG-treatment increased the number of apoptotic spermatogonia. The hCG-treatmentinduced apoptosis in spermatogonia had severe long-term consequences in reproductive functions in adulthood. Increased apoptosis after hCG-treatment was associated with subnormal testis volumes, subnormal sperm density and pathologically elevated serum FSH. This finding indicates that increased apoptosis in spermatogonia in prepuberty leads to disruption of testis development. To evaluate the role of apoptosis in human adult testes, apoptosis was induced in seminiferous tubules that were incubated under serum-free conditions in the absence or presence of testosterone. Most frequently apoptosis was identified in spermatocytes. Occasionally some spermatids also showed signs of apoptosis. In short term incubations apoptosis was suppressed by testosterone. Our findings lead to the conclusion that apoptosis is a normal, hormonally controlled phenomenon in the human testis. The role of apoptosis in disorders of spermatogenesis remains to be established.

Inhibition of sperm production in mice by annexin V microinjected into seminiferous tubules: possible etiology of phagocytic clearance of apoptotic spermatogenic cells and male infertility

“…These stages almost correspond to those of the rat spermatogenic cycle during which apoptotic cells are detectable. 1 …”

Studies on the European hare. 56. Seasonal variation of testicular activity in European brown hare Lepus europaeus

“…Apoptosis is a basic mechanism for signal-induced, selective cell elimination. This process is considered a normal, hormonally controlled phenomenon in the mammalian testis (Kerr 1992, Dym 1994, Dunkel et al 1997. The output of spermatozoa is determined largely by the shifts in degeneration vs survival of dividing and developing germ cells (Bartke 1995).…”

Caspase activity inhibition delays programmed spermatogenic cell death in vitro

“…The removal of an excess of spermatogonial cells by apoptosis has been regarded as critical during the first and successive rounds of spermatogenesis (Dunkel et al, 1997). A poorly known aspect of this well recognized process is how spermatogonial cell progenies are selected for cell death and what is the involvement of Sertoli cells in this selection process.…”

“…In the normal testis, the initial waves of proliferating spermatogonial cell progenies are programmed for cell death or apoptosis (Tapainanen et al, 1993;Furuchi et al, 1996;Suzuki et al, 1996;Dunkel et al, 1997;Rodriguez et al, 1997). The removal of an excess of spermatogonial cells by apoptosis has been regarded as critical during the first and successive rounds of spermatogenesis (Dunkel et al, 1997).…”