Research ArticleDevelopmental Biology

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

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Sci. Signal.  02 May 2017:
Vol. 10, Issue 477, eaal1910
DOI: 10.1126/scisignal.aal1910

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BMP8A activates SMAD1/5/8 and SMAD2/3 simultaneously

Like other members of the transforming growth factor–β (TGF-β) superfamily, bone morphogenetic proteins (BMPs) signal through heteromeric receptor complexes to stimulate activation of SMAD transcription factors. Whereas TGF-βs typically activate SMAD2/3, BMPs typically stimulate activation of SMAD1/5/8. Wu et al. found that BMP8A stimulated activation of both SMAD2/3 and SMAD1/5/8 in mouse spermatogonia. BMP8A acted through different sets of receptor complexes to stimulate each set of SMADs. Signaling through SMAD2/3 was important for proliferation of spermatogonia, and signaling through SMAD1/5/8 was important for the differentiation of spermatogonia into spermatids. These findings identify an unusual signaling mechanism for BMP8A and suggest that BMP8A might be useful for treating male infertility because BMP8A treatment enhanced the in vitro production of functional sperm in mouse testis explants.