Vitamin B6 promotes the activation of primordial follicles through the PI3K/Akt signaling pathway

Background Vitamins, as essential trace organic compounds for the human body, are crucial substances in the maintenance of normal reproductive function. Nevertheless, the effects of vitamins on the activation of primordial follicles and the underlying mechanisms remain unclear. Methods We used the in vitro culture model of newborn mouse ovaries to identify the vitamins that promote primordial follicle activation and study the mechanism of vitamin B6. The mechanism of VB6 was verified by in vivo injection model of newborn mice, oral feeding of adolescent mice, and in vitro culture model of human ovarian tissue. Results Thiamine monochloride (VB1), riboflavin (VB2), nicotinic acid (VB3), D-pantothenic acid (VB5), pyridoxine (VB6), folic acid (VB9), vitamin B12, L-ascorbic acid (VC), and tocopherol (VE) increased the number of growing follicles in the cultured newborn mouse ovaries. Next, we studied the molecular mechanism by using VB6. VB6 increased the protein levels of phosphorylated protein kinase B (p-Akt) and forkhead box O3a (p-FOXO3a), as well as the proportion of primordial follicle oocytes with FOXO3a nuclear export in the cultured mouse ovaries. The addition of PI3K inhibitor LY294002 blocked VB6-induced increase of growing follicles. Furthermore, intraperitoneal injection of VB6 in newborn mice and oral administration of VB6 to adolescent mice significantly increased the number of growing follicles and the protein levels of p-Akt. Importantly, VB6 also significantly increased the number of growing follicles and the protein levels of p-Akt in the cultured human ovarian tissues. Conclusion Our findings indicate that VB6 promotes primordial follicle activation through the PI3K/Akt signaling pathway.