The gene encoding bone morphogenetic protein 8B is required for the initiation and maintenance of spermatogenesis in the mouse.

Abstract

Bone morphogenetic protein 8B (BMP8B) is a member of the TGFp superfamily of growth factors. In the mouse, Bmp8b is expressed in male germ cells of the testis and trophoblast cells of the placenta, suggesting that it has a role in spermatogenesis and reproduction. To investigate these possibilities, we have generated mice with a targeted mutation in Bmp8b. Here, we show that homozygous BmpSb^^^"' mutant males exhibit variable degrees of germ-cell deficiency and infertility. Detailed analysis reveals two separable defects in the homozygous mutant testes. First, during early puberty (2 weeks old or younger) the germ cells of all homozygous mutants either fail to proliferate or show a marked reduction in proliferation and a delayed differentiation. Second, in adults, there is a significant increase in programmed cell death (apoptosis) of spermatocytes, leading to germ-cell depletion and sterility. Sertoli cells and Leydig cells appear relatively unaffected in mutants. This study therefore provides the first genetic evidence that a murine germ cell-produced factor, BMP8B, is required for the resumption of male germ-cell proliferation in early puberty, and for germ-cell survival and fertility in the adult.

SMAD expression in the testis: An insight into BMP regulation of spermatogenesis

“…Similar to mice lacking one copy of BMP4, testis development in these mutants appears normal, with effects seen only in the adult testis (Zhao et al, 1996Hu et al, 2004). Using the same reasoning as above, we suggest that, in these cases of reduced BMP expression, compensation by other BMPs is due to their ability to sufficiently activate target genes by means of the ubiquitously expressed SMAD proteins during testis development.…”

“…The survival of BMP8a Ϫ/Ϫ , BMP8b Ϫ/Ϫ , and BMP7 ϩ/Ϫ /8a mutants through embryogenesis and on to adulthood indicates that other BMPs compensate sufficiently for reduced expression or absence of these ligands (Zhao et al, 1996Hu et al, 2004). Similar to mice lacking one copy of BMP4, testis development in these mutants appears normal, with effects seen only in the adult testis (Zhao et al, 1996Hu et al, 2004).…”

“…BMP4, BMP8a, and BMP8b regulate primordial germ cell (PGC) specification in the fetus (Ying et al, 2000;Ying and Zhao, 2001), whereas in in vitro assays, BMP2 and BMP4 enhance juvenile spermatogonial proliferation (Pellegrini et al, 2003;Puglisi et al, 2004) and BMP4 can influence spermatogonial differentiation (Pellegrini et al, 2003;Baleato et al, 2005). BMP8b has also been implicated in the regulation of prepubertal germ cell proliferation at the onset of spermatogenesis, while BMP4, BMP8a and BMP8b are required for complete maintenance of adult spermatogenesis in vivo (Zhao et al, 1996;1998;Hu et al, 2004).…”

Ontogenèse des cellules germinales primordiales

“…Bmp8b interviendrait, comme Bmp4, dans la détermination des PGC, mais pas dans leur prolifération ni dans leur survie. En effet, chez certains embryons homozygotes dépourvus de Bmp8b, lorsque des PGC sont retrouvées, elles migrent et prolifèrent de façon comparable à ce qui est observé chez les embryons hétérozygotes [20,21]. [22].…”

Specific arrest of spermatogenesis caused by apoptotic cell death in transgenic mice

“…differentiation from the renewing stem cells to the meiotic cells, has been of great interest for different fields of biology (Dym 1994). At the present time, however, there is little knowledge of the regulatory mechanism of stem cell renewal and differentiation (Yoshinaga et al 1991;Dym 1994;Zhao et al 1996).…”