Rapamycin improves endometriosis‑related infertility involving ovarian senescence via the PPARα/IGFBP2 pathway.

Abstract

Endometriosis‑associated infertility is considered to be linked to cellular senescence. The present study assessed whether rapamycin, a senescence inhibitor, ameliorates endometriosis‑associated infertility by upregulating peroxisome proliferator‑activated receptor α (PPARα) and insulin‑like growth factor‑binding protein 2 (IGFBP2) expression. In the present study, mice were randomized into three groups: Control (CTL), endometriosis (EM) and rapamycin‑treated endometriosis (EM‑R). The expression of senescence‑associated markers at both the tissue and cellular levels were examined as well as the potential mechanisms underlying the effects of rapamycin treatment using ELSA and quantitative PCR. Oxidative stress markers (malondialdehyde and 8‑hydroxy‑2'‑deoxyguanosine) in peritoneal fluid were significantly elevated in the EM group compared with in the EM‑R and CTL groups, whilst antioxidant levels (superoxide dismutase and glutathione peroxidase) were lowest in the EM group. Senescence markers (p16, p21 and γH2AX) and gonadotropin receptors (follicle‑stimulating hormone receptor and luteinizing hormone receptor) were highest and lowest, respectively, in the EM group. Ovarian analysis revealed a higher primordial follicle count but fewer mature follicles in the EM group compared with the EM‑R and CTL groups. Rapamycin treatment increased PPARα and IGFBP2 expression in ovarian tissues, suggesting that its therapeutic effect on endometriosis‑related infertility may involve the PPARα/IGFBP2 pathway by mitigating cellular senescence. Rapamycin may potentially ameliorate follicular development in patients with endometriosis.