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27 The TGF-β Family in the Reproductive Tract

Stephanie A. Pangas, Martin M. Matzuk


The influence of the transforming growth factor-β (TGF-β) family on fertility and reproduction is impressive. This is true for diverse organisms from flies to humans. In Drosophila melanogaster, for example, oogenesis requires the bone morphogenetic protein (BMP)-2/4 homolog, Decapentaplegic, to maintain germ-line stem cells in the ovary (Xie and Spradling 1998) and, at later stages, for proper egg shape and polarity (Twombly et al. 1996). In mammals, various members of this family are involved from the very early stages of reproductive development, including specification of the male and female germ line and sexual differentiation. In the adult, TGF-β-related proteins govern the growth and differentiation of somatic cells as well as germ cells within the gonads. In the female, TGF-β family ligands are intricately involved in the control of ovulation and fertilization. Several of these growth factors also serve as endocrine hormones to integrate the reproductive status of the gonad to the physiological condition of the organism. Many transgenic and knockout mouse models have been created that display reproductive pathologies and highlight the importance of this family in maintaining reproductive homeostasis. These models have contributed significantly to the understanding of this protein family in reproductive processes (Matzuk et al. 1996; Elvin and Matzuk 1998; Chang et al. 2002). This chapter focuses on recent progress made in mammalian male and female reproductive biology using genetic models for the ligands, receptors, and signaling proteins of the TGF-β family.

Specification of the germ cell lineage in mammals begins in early...

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