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Highlights

As a prelude to their differentiation, Sertoli cells cease proliferation. In a paper on p. 804, Sridharan et al. used a Sertoli-cell specific conditional knockout to investigate the role of a gap junctional protein (GJA1 [also known as connexin 43, CX43]) in the cessation of proliferation of Sertoli cells that normally occurs at two weeks of age. The Sertoli cell-specific knockout causes infertility with arrest of germ cell development past spermatogonial stages, but, interestingly, Sertoli cells continue to proliferate into adulthood, similar to Sertoli cells overexpressing inhibitor of differentiation (ID) proteins, as shown previously in this journal (Chaudhary et al. Biol Reprod 2005; 72:1205–1217). Thyroid receptor alpha, THRA, normally declines as Sertoli cells age but remained high in Sertoli cells lacking GJA1 (CX43). These observations raise a number of intriguing possibilities, including promotion of mitotic arrest by cell contact through gap junctions and potential regulatory relationships among GJA1 (CX43), ID proteins and cell cycle proteins to promote differentiation of Sertoli cells.

Santhi Sridharan, Liz Simon, Daryl D. Meling, Daniel G. Cyr, David E. Gutstein, Glenn I. Fishman, Florian Guillou, and Paul S. Cooke. Proliferation of Adult Sertoli Cells Following Conditional Knockout of the Gap Junctional Protein GJA1 (Connexin 43). Biol Reprod 2007; 76:804–812. Published online ahead of print 17 January 2007; DOI 10.1095/biolreprod.106.059212

Expanding SMADness.

The LH surge induces oocyte maturation and dramatic expansion of the encompassing cumulus oophorus. Cumulus expansion in mice requires stimulation by an LH-dependent ligand—probably EGF-like peptides—and oocyte-derived enabling factors. Research reported on p. 848 by Dragovic et al. shows that a specific inhibitor of ALK4/5-dependent SMAD2/3 activation antagonizes expansion. This is the first report that cumulus expansion enabling factors act via this pathway and confirms that they are members of the TGFβ superfamily. Although activin A and B appear to be produced by mouse oocytes, follistatin, an activin antagonist, does not block the ability of oocytes to enable expansion. GDF9 is likely the major enabling factor, but other oocyte-derived members of the TGFβ1superfamily may be involved.

Rebecca A. Dragovic, Lesley J. Ritter, Samantha J. Schulz, Fred Amato, Jeremy G. Thompson, David T. Armstrong, and Robert B. Gilchrist. Oocyte-Secreted Factor Activation of SMAD 2/3 Signaling Enables Initiation of Mouse Cumulus Cell Expansion. Biol Reprod 2007; 76:848–857. Published online ahead of print 27 December 2006; DOI 10.1095/biolreprod.106.057471

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