MiR-23a represses CELF1 to modulate buffalo granulosa cell apoptosis and steroidogenesis via the PI3K/AKT pathway.

Haoxin Wang,Yun Feng,Xin Zhao,Penglei Shen,Deshun Shi,F. Lu

Published 2025 in Animal Reproduction Science

ABSTRACT

MicroRNAs (miRNAs) are critical regulators of mammalian follicle development. Our previous work showed that miR-23a expression was significantly higher in buffalo oocytes at metaphase II (MII) than at the germinal vesicle (GV) stage, implying a role in oocyte maturation. Here, we investigated the function and mechanism of miR-23a in buffalo granulosa cells (GCs). GCs cultured in vitro were transfected with miR-23a mimics or inhibitor. The miR-23a mimic markedly increased apoptosis, reduced estradiol (E2) release, elevated progesterone (P4) secretion, and suppressed the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway, whereas the inhibitor exerted the opposite effects. Dual-luciferase and rescue assays revealed that miR-23a directly targets CUG triplet repeat-binding protein 1 (CELF1). Overexpression of CELF1 reversed the pro-apoptotic effect of miR-23a, restored proliferation, normalized E2 and P4 production, and re-activated PI3K/AKT signaling. Thus, miR-23a targeted CELF1 to inhibit the PI3K/AKT pathway, promoting apoptosis, suppressing proliferation and modulating steroidogenesis in buffalo GCs, thereby controlling follicular homeostasis.

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