Migration of mesonephric cells into XY gonads is a critical early event in testis cord formation. Based on the fact that anti-Müllerian hormone (AMH) can induce testis cord formation in XX gonads, we investigated whether AMH plays a role in the induction of cell migration. Addition of recombinant AMH induced mesonephric migration into XX gonads in culture. AMH-treated XX gonads displayed increased vascular development and altered morphology of the coelomic epithelium, both features of normal testis differentiation. AMH did not induce markers of Sertoli or Leydig cell differentiation. We examined early testis development in Amh-deficient mice, but found no abnormalities, suggesting that any function AMH may have in vivo is redundant. Other transforming growth factor (TGF-β) family proteins, bone morphogenetic proteins (BMP2 and BMP4) show similar inductive effects on XX gonads in culture. Although neither BMP2 nor BMP4 is expressed in embryonic XY gonads, our findings suggest that a TGF-β signalling pathway endogenous to the XY gonad may be involved in regulation of mesonephric cell migration. The factors involved in this process remain to be identified.
IkappaBalpha and IkappaBbeta are regulators of the nuclear factor-kappaB (NF-kappaB) transcription factor family. Both IkappaBs bind to the same NF-kappaB dimers and are widely expressed in different cells and tissues. To better understand how these two IkappaB isoforms differ biologically, we have characterized the expression of IkappaBbeta in testis, a tissue in which IkappaBalpha is only minimally expressed. We have found that IkappaBbeta expression is localized within the haploid spermatid stages of spermatogenesis and follows the expression of nuclear NF-kappaB. IkappaBbeta expression in haploid spermatids is likely regulated by Sox family proteins, members of which are also expressed within spermatids. We have shown that both SRY and Sox-5 can bind to multiple Sox binding sites found within the IkappaBbeta promoter and can enhance transcription of a reporter gene in transient transfection assays. We also demonstrate that IkappaBbeta mRNA is strongly expressed in developing male gonads. These results therefore suggest that IkappaBbeta may be a novel target for transcription factors of the HMG-box SRY/Sox family and imply a potential role for NF-kappaB/IkappaBbeta in spermatogenesis.
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