TSPYL2 regulated by miR-301a-3p contributes to impaired decidualization in polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders associated with female infertility. Increasing evidence suggests that impaired endometrial receptivity, in addition to ovulatory dysfunction, may contribute to infertility in women with PCOS. However, the molecular mechanisms underlying defective decidualization in PCOS remain poorly understood. We observed impaired decidualization in both a prenatally androgenized mouse model and primary endometrial stromal cells from patients with PCOS. Testis-specific Y-encoded-like protein 2 (TSPYL2) displayed aberrant expression dynamics in PCOS, with elevated expression in the proliferative phase but insufficient induction during decidualization. Silencing TSPYL2 impaired decidualization and reduced implantation capacity in vitro and in vivo. Transcriptomic analysis further showed that TSPYL2 knockdown was associated with increased cell-cycle-associated signatures and reduced expression of hormone-responsive, decidualization- and endometrial receptivity-associated genes. Serum miR-301a-3p was upregulated during the secretory phase in PCOS and directly targeted the 3′ untranslated region of TSPYL2, suppressing its expression. Our findings suggest that elevated miR-301a-3p may impair decidualization by targeting TSPYL2, thereby contributing to defective endometrial function in PCOS.