• PMID: 28465413
• Gene Name: BMP8A
• Condition: Role in sustaining spermatogenesis
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Role in sustaining spermatogenesis

BMP8A sustains spermatogenesis by activating both SMAD1/5/8 and SMAD2/3 in spermatogonia

Wu FJ, Lin TY, Sung LY, Chang WF, Wu PC, Luo CW.

Mutation in either of the genes encoding bone morphogenetic protein (BMP) 8A or 8B (Bmp8a or Bmp8b) causes postnatal depletion of spermatogonia in mice. We found that Bmp8a, but not Bmp8b, was expressed predominantly in the neonatal mouse spermatogonia. Although most BMPs induce activation of SMADs 1, 5, and 8 (SMAD1/5/8), but not SMADs 2 and 3 (SMAD2/3), we found that BMP8A induced signaling through both sets of transcription factors. In undifferentiated mouse spermatogonia, BMP8A activated SMAD1/5/8 through receptor complexes formed by ALK3 and either ACVR2A or BMPR2 and activated SMAD2/3 through receptor complexes formed by ALK5 and ACVR2A, ACVR2B, or TGFBR2. Signaling through SMAD2/3 promoted the proliferation of germ cells, whereas that through SMAD1/5/8 directed the subsequent differentiation of spermatogonia. BMP8A promoted spermatogenesis in cultured mouse testis explants, and the resulting spermatids were functionally competent for fertilization. These results suggest that the dual role of BMP8A in promoting proliferation and differentiation of spermatogonia may be exploited clinically to treat male infertility. CI - Copyright © 2017, American Association for the Advancement of Science. FAU - Wu, Fang-Ju AU - Wu FJ AUID- ORCID: 0000-0002-7933-3312 AD - Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan. FAU - Lin, Ting-Yu AU - Lin TY AD - Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan. FAU - Sung, Li-Ying AU - Sung LY AD - Institute of Biotechnology, National Taiwan University, Taipei 106, Taiwan. FAU - Chang, Wei-Fang AU - Chang WF AUID- ORCID: 0000-0001-8754-5991 AD - Institute of Biotechnology, National Taiwan University, Taipei 106, Taiwan. FAU - Wu, Po-Chih AU - Wu PC AD - Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan.