Sodium Butyrate Promotes In Vitro Development of Mouse Preantral Follicles and Improves Oocyte Quality by Regulating Steroidogenesis, Oxidative Stress, and Cytoskeleton Remodeling
by
and
Xiaohuan Liu
1,†,
Tuba Latif Virk
1,†,
Mengdie Pi
1,
Qi Liu
1,2,3,
Sheng Yang
1,2,3,
Zhiyu Ma
1,2,3,
Yuguo Yuan
1,2,3
and
Fenglei Chen
1,2,3,* 1
College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China
2
Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China
3
Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Animals 2025, 15(24), 3567; https://doi.org/10.3390/ani15243567
Submission received: 23 October 2025
/
Revised: 3 December 2025
/
Accepted: 9 December 2025
/
Published: 11 December 2025
(This article belongs to the Special Issue Mechanisms of Reproductive Dysfunction in Animals: From Cellular Insights to Environmental Insults)
Simple Summary
Sodium butyrate (NaBu) is a natural compound that is commonly used as a feed additive to improve the growth and health of animals, but its direct influence on follicular development has not been clearly understood. In this study, a three-dimensional (3D) culture system of mouse follicles was used to examine the effects of NaBu on follicular growth, hormone secretion, and the development of oocytes. Our results showed that NaBu could promote follicular growth and maturation, increase estrogen secretion, maintain healthy follicular structure, and enhance oocyte quality by improving cytoskeletal organization and reducing oxidative stress. It also supported communications between oocytes and ovarian granulosa cells, contributing to better follicular function. Although early embryonic development after fertilization did not show a significant difference, NaBu effectively improved the overall developmental potential of the follicles and oocytes. These findings suggest that NaBu has significant potential as a regulatory factor for optimizing in vitro follicular culture systems and improving the quality of oocytes, with broad application prospects in animal reproduction and assisted reproductive technologies.
Abstract
Sodium butyrate (NaBu), a common feed additive, has been shown to enhance reproductive performance in livestock and poultry. However, whether NaBu exerts this effect by directly regulating follicular development remains unclear. In this study, a three-dimensional (3D) in vitro culture system of mouse preantral follicles was used to investigate the effects of NaBu on follicular growth, hormone secretion, maturation of oocytes, and subsequent embryonic development. Preantral follicles were treated with different doses of NaBu on the fourth day of culture. Subsequently, the mature oocytes (MII stage) were released from the follicles on the ninth day and subjected to parthenogenetic activation for developmental assessment. The results showed that 0.10 mM NaBu treatment could significantly promote follicular growth, antral formation, and oocyte maturation. Furthermore, NaBu also significantly increased estradiol (E2) secretion, improved follicular structure, and maintained cellular viability. qPCR analysis revealed that NaBu significantly increased the mRNA levels of STAR, CYP11A1, and CYP1B1. In addition, it significantly enhanced the distribution and organization of F-actin, with increases in the mRNA levels of GDF9, BMP15, and CX37. NaBu treatment significantly reduced intracellular ROS levels and increased the mRNA levels of NRF2 and SOD1, while SOD2 and GSR showed increasing trends without significant differences. NaBu significantly improved oocyte cytoskeletal organization and the morphology of the spindle, but it did not lead to a significant increase in the rates of cleavage and blastocyst formation after parthenogenetic activation. Collectively, these findings indicate that NaBu promotes follicular development and improves oocyte quality, at least partly, by enhancing steroidogenesis, alleviating oxidative stress, and maintaining cytoskeletal integrity, providing insight into its potential application for improving reproductive performance in livestock and poultry.
Keywords:
sodium butyrate; preantral follicle; oocyte; oxidative stress; mouse
