Jinlun Lu

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.

Circadian rhythm disruptions and heat stress can cause gut microbiota dysbiosis and intestinal barrier damage, increasing the risk of inflammatory bowel disease. However, whether eating according to the circadian rhythm during the day when the ambient temperature is higher or eating against the circadian rhythm at night when the ambient temperature is relatively suitable, is better for the gut health of diurnal animals in summer has not been clarified. In this study, growing pigs were randomly assigned to a daytime‐restricted feeding or nighttime‐restricted feeding (NRF) group and raised for 18 days in summer with mild heat stress. Our results showed that NRF alleviated heat stress in pigs, as reflected by increased feed intake and decreased drinking. Microbiome analysis revealed that NRF increased the diversity of gut microbiota and abundance of short‐chain fatty acids (SCFAs)‐producing bacteria and decreased the abundance of gram‐negative and potentially pathogenic bacteria, thereby increasing SCFAs and reducing lipopolysaccharide production in the colon. These changes enhanced colonic barrier function and reduced colitis and systemic inflammation by upregulating tight junction proteins and mucin. Our findings indicate that although nighttime eating does not align with the biological habits of pigs, consuming food at a relatively suitable ambient temperature is more beneficial for gut health and homeostasis during hot seasons. Our research provides a reference for guiding the healthy feeding of farm animals in summer and a basis for developing a lifestyle that promotes gut health for individuals in tropical regions.

In vitro embryo production depends on high-quality oocytes. Compared with in vivo matured oocytes, in vitro oocytes undergo precocious meiotic resumption, thus compromising oocyte quality. C-type natriuretic peptide (CNP) is a follicular factor maintaining meiotic arrest. Thus, CNP-pretreatment has been widely used to improve the in vitro maturation (IVM) of oocytes in many species. However, the efficacy of this strategy has remained unsatisfactory in porcine oocytes. Here, by determining the functional concentration and dynamics of CNP in inhibiting spontaneous meiotic resumption, we improved the current IVM system of porcine oocytes. Our results indicate that although the beneficial effect of the CNP pre-IVM strategy is common among species, the detailed method may be largely divergent among them and needs to be redesigned specifically for each one. Focusing on the overlooked role of cumulus cells surrounding the oocytes, we also explore the mechanisms relevant to their beneficial effect. In addition to oocytes per se, the enhanced anti-apoptotic and anti-oxidative gene expression in cumulus cells may contribute considerably to improved oocyte quality. These findings not only emphasize the importance of screening the technical parameters of the CNP pre-IVM strategy for specific species, but also highlight the critical supporting role of cumulus cells in this promising strategy.

Significance: The fertility of female mammals depends upon the well-orchestrated progression of oocyte meiosis, the female germ cell division that is essential for haploid oocyte formation. In preovulatory follicles, how LH induces a decrease in CNP and its encoding mRNA Nppc , a prerequisite for oocyte meiotic resumption, remains an outstanding question to understand the mechanism that controls oocyte meiosis. The present study shows that TTP, an mRNA-destabilizing protein, is one of the regulatory components responsible for the LH-induced rapid decrease in Nppc mRNA and oocyte meiotic resumption. This finding not only highlights the importance of posttranscriptional regulation in the follicle periphery to fine-tune oocyte meiosis but also provides an insight into CNP-dependent cGMP homeostasis in other physiological systems.