SH2-B Is Required for Both Male and Female Reproduction

Many growth factors and hormones modulate the reproductive status in mammals. Among these, insulin and insulin-like growth factor I (IGF-I) regulate the development of gonadal tissues. SH2-B has been shown to interact with insulin and IGF-I receptors, although the role of SH2-B in these signals has not been clarified. To investigate the role of SH2-B, we generated mice with a targeted disruption of the SH2-B gene. Both male and female SH2-B(−/−) mice showed slight retardation in growth and impaired fertility. Female knockout mice possess small, anovulatory ovaries with reduced numbers of follicles and male SH2-B(−/−) mice have small testes with a reduced number of sperm. SH2-B(−/−) cumulus cells do not respond to either follicle-stimulating hormone or IGF-I. These data suggest that SH2-B plays a critical role in the IGF-I-mediated reproductive pathway in mice.