Functional Characterization of IGF2BP1, CDC25A, and RXFP2 Genes: Implications for Ovarian Function and Reproductive...

Goat reproductive performance is a key determinant of the productivity and economic value of goat farming, especially in meat and milk production. In a previous study, to investigate the genetic basis of prolificacy, we divided goats into groups according to their consistent reproductive performance (producing either single kids or twins) over five consecutive kidding cycles, and performed whole-genome resequencing and RNA-seq analysis on their ovarian tissues. Through integrated analysis, we identified three candidate genes-IGF2BP1 (insulin-like growth factor 2 mRNA-binding protein 1), CDC25A (cell division cycle 25A), and RXFP2 (relaxin family peptide receptor 2)-as potential key regulators of reproductive capacity. Using goat ovarian granulosa cells, we systematically assessed the impact of each gene through gain- and loss-of-function experiments. Overexpression of IGF2BP1 promoted cell proliferation and suppressed apoptosis, underscoring its role in maintaining cellular viability. Conversely, its knockdown significantly impeded growth and induced cell death. Similarly, CDC25A enhanced granulosa cell proliferation, whereas its knockdown led to marked growth impairment and increased apoptosis. Proliferation was also enhanced by RXFP2 overexpression but impaired upon its knockdown, suggesting that RXFP2 is functionally important for follicular development. Collectively, these findings establish IGF2BP1, CDC25A, and RXFP2 as fundamental regulators of granulosa cell dynamics and ovarian follicular development, providing crucial functional insights and promising targets for genetic selection to enhance reproductive efficiency in goats.