# Functional Characterization of IGF2BP1, CDC25A, and RXFP2 Genes: Implications for Ovarian Function and Reproductive Regulation in Goats

## TL;DR

This study identifies three genes that are crucial for goat reproduction, showing they support cell growth and egg development, which could help improve goat farming productivity.

## Contribution

The study functionally characterizes IGF2BP1, CDC25A, and RXFP2 as key regulators of granulosa cell dynamics in goats.

## Key findings

- Overexpression of IGF2BP1 promotes granulosa cell proliferation and suppresses apoptosis.
- CDC25A enhances granulosa cell proliferation, while its knockdown increases apoptosis.
- RXFP2 supports follicular development, as its overexpression enhances proliferation and its knockdown impairs it.

## Abstract

Goats that consistently produce twins are more valuable than those bearing single offspring, so understanding the biological basis of this difference is important for agriculture. The research focused on genes active in ovarian tissues, specifically within granulosa cells—specialized cells that surround and support developing eggs. By investigating the genes IGF2BP1, CDC25A, and RXFP2, the team found that increasing their activity promoted the proliferation and survival of granulosa cells, which are essential for follicle development. Conversely, suppressing these genes inhibited cell growth and triggered cell death. These results demonstrate that all three genes play vital roles in maintaining ovarian cell health and supporting egg development, providing insights into why some goats are more prolific. In the long term, this knowledge could inform selective breeding programs, enabling farmers to choose goats with favorable genetic traits for larger, healthier litters. This would improve the productivity and sustainability of goat farming, benefiting food production and rural livelihoods.

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.