Choline-Mediated Regulation of Follicular Growth: Interplay Between Steroid Synthesis, Epigenetics, and Oocyte Development.

This review article focuses on the role of choline in ovarian follicular development, regulated by nutrient-epigenetic interactions. Choline, a key feed additive, participates in DNA methylation and steroid hormone synthesis via its methyl donor function. However, its role in follicular hierarchy and maturation is unclear. Research lacks an understanding of species-specific choline metabolism, follicular fluid methylation dynamics, and toxicity thresholds. This study combines animal nutrition, epigenetics, and reproductive endocrinology. Using in vitro follicle culture models, metabolomics analysis, and cytochrome P450 family 19 subfamily A member 1 (CYP19a1) methylation site screening, it reveals that choline regulates follicle hierarchy through the betaine-S-adenosylmethionine (SAM) pathway. Proper dietary choline reduces homocysteine (HCY) and boosts CYP19a1 demethylation, enhancing theca cell estradiol (E₂) production and accelerating follicle maturation. In contrast, inadequate or excessive choline causes mesoderm-specific transcript (MEST) gene methylation abnormalities or trimethylamine N-oxide (TMAO)-mediated β-oxidation inhibition, increasing follicle atresia. A phenomenon of steroidogenic factor 1 (SF-1) methylation has been observed in poultry, showing that choline affects offspring egg-laying persistence by altering the adrenal-ovarian axis DNA methylation imprint. Future research should establish a precise choline supply system based on the HCY/TMAO ratio in follicular fluid and the CYP19a1 methylation map to improve animal reproduction.