Induction of autophagy by Beclin-1 in granulosa cells contributes to follicular progesterone elevation in ovarian endometriosis
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Beclin-1 mediated autophagy in granulosa cells was found to increase follicular progesterone levels in ovarian endometriosis.
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Abstract
Endometriosis is a common gynecological disease in which ovarian dysfunction can be an important cause of infertility. Elevated progesterone (P4) levels during the follicular phase is possibly associated with impaired oocyte quality and pregnancy outcome in endometriosis. Beclin-1 (BECN1), an essential mediator of autophagy, has been shown to be related to the development and progression of endometriosis. This study aimed to investigate the autophagic activity in ovarian granulosa cells (GCs) of patients with endometriosis and to clarify the role of BECN1 in preovulatory P4 elevation. Our results demonstrated that serum P4/estradiol (E2) ratio and P4-to-follicle index (the average P4 secretion per follicle) on the day of human chorionic gonadotropin administration were elevated in women with ovarian endometriosis. Increased expression of BECN1 and enhanced autophagy were observed in GCs of patients with ovarian endometriomas. In cultured GCs, BECN1 knockdown reduced P4 secretion and the expression of key steroidogenic enzymes; whereas overexpression of BECN1 resulted in induced P4 production with activated biosynthesis pathway. Moreover, inhibition of autophagy by BECN1 knockdown significantly attenuated low-density lipoprotein (LDL)-induced P4 synthesis. These findings provide new insights into the role of BECN1 in late follicular P4 elevation in patients with endometriosis by promoting the degradation pathway of LDL for P4 biosynthesis via lysosome activation in GCs, and have potential therapeutic implications for the improvement of oocyte quality in women affected by endometriosis.
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Cited by (14)
- Evidence for KISS-1 nuclear translocation and PI3K/AKT signaling in the ultrastructurally and morphometrically analyzed human endometriosis 2026
- Mechanisms of Endometrioma-Mediated Ovarian Damage: Myths and Facts 2025
- Dysregulated autophagy in endometriosis: molecular mechanisms, controversies, and clinical implications 2025
- Impact of the Endometriomas on the Ovarian Follicles 2024
- The Effect of Endometriosis on the Quality of Oocytes and Embryos Obtained by IVF 2024
- Transcription factor EB-mediated autophagy affects cell migration and inhibits apoptosis to promote endometriosis 2024
- Molecular mechanism of autophagy and apoptosis in endometriosis: Current understanding and future research directions 2024
- Bushen Wenyang Huayu Decoction inhibits autophagy by regulating the SIRT1-FoXO-1 pathway in endometriosis rats 2023
- Research advances in endometriosis-related signaling pathways: A review 2023
- hsa-miR-340-5p inhibits epithelial–mesenchymal transition in endometriosis by targeting MAP3K2 and inactivating MAPK/ERK signaling 2022
- miR‑143‑3p inhibits endometriotic stromal cell proliferation and invasion by inactivating autophagy in endometriosis 2021
- The impact of phthalate on reproductive function in women with endometriosis 2021
- New understanding of TFEB and autophagy in the development of endometriosis:review 2020
- cGAS-STING pathway participates in endometriosis by up-regulating autophagy:Review. 2020
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