The Role of TGF-β Signaling Pathway in Determining Small Ruminant Litter Size

Abstract

The transforming growth factor-beta (TGF-β) superfamily plays a crucial role in regulating female reproductive traits, particularly litter size, in small ruminants, such as sheep and goats. This review comprehensively examines the molecular mechanisms through which TGF-β superfamily members-including bone morphogenetic proteins (BMPs), growth differentiation factor 9 (GDF9), inhibin (INHA and INHB), and associated signaling genes-influence ovarian follicular development, ovulation rate, and ultimately, litter size. We synthesize recent findings on polymorphisms in key genes, such as BMPR1B, BMP15, GDF9, inhibins and SMADs family genes, across diverse sheep and goat breeds worldwide. The manuscript highlights how specific mutations in these genes create an intricate signaling network that modulates granulosa cell proliferation, follicular sensitivity to FSH, and the prevention of dominant follicle selection. These molecular interactions result in increased ovulation rates and larger litter sizes in prolific breeds. The gene dosage effects observed in heterozygous versus homozygous mutation carriers further illuminate the complex nature of these reproductive regulations. This improved the understanding of the genetic basis for prolificacy provides valuable insights for marker-assisted selection strategies aimed at enhancing reproductive efficiency in small ruminant breeding programs, with significant implications for improving livestock productivity and economic outcomes.

Keywords: AMH; BMPs; GDF9; Inhibin; SMADs; goat; litter size; sheep.

Figure 1

Effects of AMH, SMADs, and Inhibins on litter size in sheep and goats.

Figure 2

Crosstalk between TGF-β signaling members and their association with litter size in sheep and goats. This figure depicts signaling pathways in ovarian follicles mediated by TGF-β superfamily members. GDF9, BMPs, and inhibins activate distinct SMAD-dependent pathways that regulate fertility genes and control follicular development. Mutations in GDF9, BMPR1B, and BMP15 alter these pathways, affecting ovulation rates and litter size. Inhibins modulate the process by blocking FSH action. These integrated pathways collectively determine follicular growth dynamics and reproductive outcomes. Note: “TFs” stands for transcription factors.