E₂/ER signaling mediates the meiotic arrest of goat intrafollicular oocytes induced by follicle-stimulating hormone

The increased production of high-quality oocytes lies at the heart of the search to accelerate the reproduction of high-quality breeding livestock using assisted reproductive technology. Follicle-stimulating hormone (FSH) maintains the arrest of oocyte meiosis during early follicular development in vivo and promotes the synchronous maturation of nucleus and cytoplasm to improve oocyte quality. However, the mechanism by which FSH maintains meiotic arrest in oocytes is still not fully understood. Oocytes spontaneously resume meiosis once released from the arrested state. In this study, we isolated goat antral follicles with a diameter of 2.0-4.0 mm, cultured them in vitro either with or without added FSH, and finally collected the oocytes to observe their meiotic state. The results showed that FSH effectively inhibited the meiotic recovery of oocytes in follicles [4 h: control (n = 84) vs. with FSH (n = 86), P = .0115; 6 h: control (n = 86) vs. FSH (n = 85), P = 0.0308; and 8 h: control (n = 95) vs. FSH (n = 101), P = 0.0039]. FSH significantly inhibited the downregulation of natriuretic peptide receptor 2 (NPR2) expression and cyclic guanosine monophosphate (cGMP) synthesis during follicular culture in vitro (P < 0.05). Further exploration found that FSH promoted the synthesis of 17 beta-estradiol (E-2) (P = .0249 at 4 h and P = .0039 at 8 h) and maintained the expression of the estrogen nuclear receptor ER beta, but not the estrogen nuclear receptor ER alpha during follicle culture in vitro (P = .0190 at 2 h, and P = .0100 at 4 h). In addition, E-2/ER (estrogen nuclear receptors ER alpha and ER beta) mediated the inhibitory effect of FSH on the downregulation of NPR2 expression and cGMP synthesis, ultimately preventing the meiotic recovery of oocytes (P < .05). In summary, our study showed that FSH-induced estrogen production in goat follicles, and the E-2/ER signaling pathway, both mediated meiotic arrest in FSH-induced goat oocytes.