An early and massive wave of germinal cell apoptosis is required for the development of functional spermatogenesis

Abstract

hormonally regulated. That a proper balance between cell death and survival-promoting proteins is critical to achieve Transgenic mice expressing high levels of the BclxL or this physiological apoptotic wave at an early stage of Bcl2 proteins in the male germinal cells show a highly testicular germinal cell differentiation is substantiated by abnormal adult spermatogenesis accompanied by the finding of a comparable syndrome in mice defective sterility. This appears to result from the prevention of in the bax gene (Knudson et al., 1995). This early an early and massive wave of apoptosis in the testis, apoptotic wave of germ cells during establishment of which occurs among germinal cells during the first spermatogenesis may be required to maintain a proper round of spermatogenesis. In contrast, sporadic cell number ratio between maturing germ cells and Sertoli apoptosis among spermatogonia, which occurs in nor-cells. An intricate relationship involving a constant modumal adult testis, is not prevented in adult transgenic lation of activity and exchange of differentiation signals mice. The physiological early apoptotic wave in the indeed exists between these two cell types (reviewed in testis is coincident, in timing and localization, with a Jegou, 1993) from the first stage of spermatogenesis, and temporary high expression of the apoptosis-promoting its perturbation may extend to the life-long process of protein Bax, which disappears at sexual maturity. mature spermatogenesis. The critical role played by the intracellular balance, probably hormonally controlled, of the BclxL and Bax proteins (Bcl2 is apparently not expressed in normal Results mouse testis) in this early apoptotic wave is shown byMale transgenic mice expressing Bcl2 or the occurrence of a comparable testicular syndrome in overexpressing BclxL in their germinal cells are mice defective in the bax gene. The apoptotic wave sterile and display marked alterations in the late appears necessary for normal mature spermatogenesis stages of spermatogenesis to develop, probably because it maintains a critical cellMice bearing a human bcl2 or a human bclx transgene number ratio between some germinal cell stages and placed under the control of the promoter of the murine Sertoli cells, whose normal functions and differentihousekeeping phosphoglycerate kinase-1 (pgk-1) gene ation involve an elaborate network of communication.were generated. One male and four female founders Keywords: apoptosis/germinal cells/spermatogenesis/ bearing a bcl2 transgene were obtained. The male (T41) transgenic was sterile and one of the females (T56) showed a lack of vaginal opening at sexual maturity. The ovaries of this founder female were, however, functional, since, when grafted onto ovariectomized normal female mice, they

E2F1 controls germ cell apoptosis during the first wave of spermatogenesis

“…correct Sertoli/germ cell‐ratio for the successive rounds of spermatogenesis is established during the first wave of spermatogenesis (Shaha et al ., 2010). Important effectors of the first‐wave apoptosis are the pro‐apoptotic Bax and anti‐apoptotic Bcl‐w, Bcl‐X L and Bcl‐2 (Knudson et al ., 1995; Furuchi et al ., 1996; Rodriguez et al ., 1997; Yan et al ., 2003; Jahnukainen et al ., 2004). Ablation of Bax or over‐expression of the anti‐apoptotic factors (Bcl‐2 or Bcl‐X L ) result in disruption of spermatogenesis because of eliminated first‐wave apoptosis.…”

Neonatal Gonocyte Differentiation in Mongolian GerbilMeriones unguiculatusInvolves Asynchronous Maturation of Seminiferous Cords and Rapid Formation of Transitional Cell Stage

“…Gn apoptosis ensures a critical degree of selection in providing an appropriate germ cell population and its mechanisms have been partially elucidated (Rodriguez et al, 1997;Boulogne et al, 1999;Wu et al, 2005;Basciani et al, 2008). Apoptotic peaks were detected in gerbils before (7 d) and after (21 d), when the bulk of Gn relocation and levels were one third those found in rats (Boulogne et al, 1999).…”

“…This pattern, however, does not seem to be common to all rodents, since mice lack a neonatal apoptosis peak and Gn degenerate by necrosis (Wang et al, 1998). The Gn relocation to the basement membrane of seminiferous epithelium, during the neonatal period, is critical for its survival, because Gn that remain within the tubule center degenerate (RoosenRunge and Leik, 1968;Rodriguez et al, 1997). In rats, the relocation begins one day after neonatal proliferation which suggests that these events are independent and probably regulated by different mechanisms (McGuinness and Orth, 1992a).…”

P53 levels determine outcome during β-catenin tumor initiation and metastasis in the mammary gland and male germ cells

“…Furthermore P53 is important for the proper occurrence of two waves of apoptosis during spermatogenesis, occurring at E16.5 and at 14 days postpartum (Rodriguez et al, 1997). These apoptotic waves are thought to establish the correct cell numbers in the seminiferous tubules and remove any cells that have acquired mutations owing to the rapid proliferation that occurs during the initial wave of spermatogenesis.…”