Lactational high weight loss impairs follicular development by causing mitochondrial dysfunction of ovarian cells in sows and mitigated by butyrate supplement.

INTRODUCTION: In modern sows, lactational high weight loss (HWL), caused by the large litter size and inadequate feed intake, has a negative effect on follicular development after weaning, resulting in poor reproductive performance in the subsequent parity. However, the underlying mechanism remains unclear. OBJECTIVES: This research aimed to explore the mechanism that sows HWL during lactation damages follicular development and attempt to improve the reproductive function by treating with butyrate. METHOD: Four multiparous sister sows were chosen to build a HWL model for lactating sows through feed restriction during the final week of a 21-day lactation. Spatially transcriptomics (ST) and tissue immunofluorescent staining were then utilized for the antral follicles in the ovarian surface to search for differentially expressed genes and proteins among different cell types. Subsequently, the mouse assay, including immunofluorescent staining, transmission electron microscopy, hormone detection and western blot, were conducted to verify the findings in sows and investigate the effect of butyrate on the follicular development in HWL mice. RESULTS: Based on the transcriptomic analysis, differentially expressed genes in granulosa cells, theca cells, and ovarian stromal cells were examined. The findings revealed that HWL disturbs the mitochondrial electron transport chain and steroidogenesis in all three cell types by downregulating the expression of NDUFB3, SDHB, CYCS, COX8A and CYP19A1, as well as upregulating the expression of STAR, CYP11A1 and CYP17A1. Furthermore, results from mouse assays demonstrated that HWL causes apoptosis and alters sex hormone secretion by impairing mitochondrial function and disordering the expression of steroidogenesis key enzymes in ovarian cells, while these effects were partially mitigated by butyrate treatment. CONCLUSION: The mitochondrial dysfunction and abnormal steroidogenesis induced by HWL during lactation in ovarian cells harm the follicular development of weaning sows, which could be alleviated by butyrate treatment.