Upregulation of PD-L1 contributes to improving the apoptosis of granulosa cells via the PI3K/AKT pathway in PCOS.

Autor: Han R; Department of Prenatal Diagnosis, Center for Reproductive Medicine, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.; State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi, China.; Xinjiang Clinical Research Center for Reproductive Immunology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China., Zhu Y; Department of Reproductive Assistance, Center for Reproductive Medicine, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China., Zhang X; Department of Reproductive Assistance, Maternal and Child Health Hospital of Xinjiang Uyghur Autonomous Region, Urumqi, China., Liu X; Department of Prenatal Diagnosis, Center for Reproductive Medicine, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China., Xia Y; Department of Prenatal Diagnosis, Center for Reproductive Medicine, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China., Ye E; Department of Prenatal Diagnosis, Center for Reproductive Medicine, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China., La X; State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi, China. 909232905@qq.com.; Xinjiang Clinical Research Center for Reproductive Immunology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China. 909232905@qq.com.; Center for Reproductive Medicine, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China. 909232905@qq.com.; Department of Prenatal Diagnosis, First Affiliated Hospital of Xinjiang Medical University, No.137 Liyushan Road, Xinshi District, Urumqi, Xinjiang Uygur Autonomous Region, China. 909232905@qq.com., Ding J; State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi, China. 1601379937@qq.com.; Department of Prenatal Diagnosis, First Affiliated Hospital of Xinjiang Medical University, No.137 Liyushan Road, Xinshi District, Urumqi, Xinjiang Uygur Autonomous Region, China. 1601379937@qq.com.
Jazyk: angličtina
Zdroj: Journal of assisted reproduction and genetics [J Assist Reprod Genet] 2024 Dec 11. Date of Electronic Publication: 2024 Dec 11.
DOI: 10.1007/s10815-024-03327-y
Abstrakt: Purpose: Polycystic ovary syndrome (PCOS) is a leading cause of anovulatory infertility and closely correlated with apoptosis in ovarian granulosa cells (GCs). Programmed cell death protein-1/programmed cell death ligand-1 (PD-1/PD-L1) pathway plays an important role throughout gestation and the pathogenesis of adverse pregnancy outcomes, but its mechanism in PCOS remains unclear.
Methods: The RNA sequencing data for PCOS patients were downloaded from the Gene Expression Omnibus (GEO) databases. Bioinformatics analysis was conducted to identify differentially expressed PD-1/PD-L1 pathway genes (DEPPGs) and related signaling pathways. PCOS mouse model was established by injecting dehydroepiandrosterone (DHEA), apoptosis of ovarian GCs in PCOS mouse were detected by TUNEL staining. The main genes and proteins in the PI3K/AKT signaling pathway and apoptosis were detected by qRT-PCR and Western blot analyses after PD-L1 intervention in GCs. Finally, the hub gene of differentially expressed PI3K/AKT pathway genes (DEPAGs) in GCs was evaluated in PCOS patients.
Results: The DEPPGs in GCs and oocyte were identified, showing enrichment in Th1 and Th2 cell differentiation, apoptosis, and PI3K/AKT signaling pathway. More apoptosis was observed in ovarian GCs of PCOS mice. In vitro experiments showed that PI3K/AKT pathway was activated and the apoptosis of GCs was suppressed after PD-L1 intervention. The hub gene COL1A1 was upregulated in the GCs of PCOS patients.
Conclusions: PD-L1 may reduce the apoptosis of GCs through PI3K/AKT signaling pathway activation, providing a novel strategy for inhibiting the apoptosis of GCs in PCOS.
Competing Interests: Declarations. Ethical approval: The First Affiliated Hospital of Xinjiang Medical University's Ethics Committee approved the study (Ethical Approval Number K202305-02), and all individual signed the informed consent form. Conflict of interest: The authors declare that there are no direct or indirect conflicts of interest related to the content, conclusions, or interpretation of the study titled “Upregulation of PD-L1 contributes to improving the apoptosis of granulosa cells via the PI3K/AKT pathway in PCOS,” submitted to the Journal of Assisted Reproduction and Genetics. We confirm that no funding, goods, or services have been received that could potentially influence the impartiality of this research. In addition, the authors have no affiliations or collaborations with any organizations or individuals that have a direct or indirect competing interest in this research.
(© 2024. The Author(s).)
Databáze: MEDLINE
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