The Anti-Apoptotic Effect of C-Type Natriuretic Peptide and the Regulation of NPPC in Porcine Ovarian Granulosa Cells

TL;DR

This study explores how C-type natriuretic peptide (CNP) affects porcine ovarian granulosa cells and regulates NPPC expression, revealing new insights into follicular development.

Contribution

The study identifies novel regulatory mechanisms of NPPC expression and CNP's anti-apoptotic role in porcine granulosa cells.

Findings

Follicular atresia in pigs is linked to reduced CNP receptor NPR2 levels.

Estradiol promotes NPPC expression and enhances CNP's anti-meiotic effect.

EGF signaling downregulates NPPC via ERK-activated tristetraprolin.

Abstract

C-type natriuretic peptide (CNP), encoded by the NPPC (Natriuretic Peptide Precursor C), has been recognized as the principal endogenous factor sustaining oocyte meiotic arrest in mammalian follicles. Yet its influence on porcine ovarian granulosa cell fate and the regulatory mechanism of NPPC expression within these cells remain poorly understood. Here, utilizing an in vitro culture model of primary porcine ovarian granulosa cells and immature oocytes, we examined the impact of CNP on granulosa cell apoptosis and oocyte meiotic resumption, and elucidated the molecular circuitry governing NPPC expression. We found that follicular atresia in pigs was accompanied by a marked decline in the CNP receptor NPR2 (natriuretic peptide receptor 2). Correspondingly, exogenous CNP suppressed apoptosis in cultured porcine granulosa cells. Estradiol can significantly promote the expression level of NPPC in porcine ovarian granulosa cells and, by enhancing NPR2 levels, it can synergize with CNP to inhibit oocyte meiotic resumption in vitro. Conversely, EGF signaling can significantly downregulate NPPC mRNA expression in porcine granulosa cells, an effect likely mediated by ERK-activated tristetraprolin (TTP). Collectively, these findings broaden our understanding of CNP in follicular development and delineate the endocrine network that controls NPPC transcription in the porcine ovary.

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