利拉鲁肽通过抑制CXCL10分泌改善多囊卵巢综合征患者的卵泡发育。

IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Reproductive Biology and Endocrinology Pub Date : 2024-08-06 DOI:10.1186/s12958-024-01269-9
Min Zhao, Baoying Liao, Chuyu Yun, Xinyu Qi, Yanli Pang
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引用次数: 0

摘要

背景:目前,GLP-1受体激动剂利拉鲁肽治疗多囊卵巢综合征(PCOS)的临床试验已经开展了多项。然而,利拉鲁肽对卵泡发育的影响及其具体机制仍不清楚:方法:采用RNA测序技术探讨了利拉鲁肽治疗多囊卵巢综合征患者颗粒细胞的分子特征。ELISA法检测卵泡液中C-X-C基调趋化因子配体10(CXCL10)的水平,qPCR法检测卵泡和颗粒细胞中排卵相关基因和炎症因子基因的表达水平,Western印迹法检测连接蛋白43(Cx43)、Janus激酶2(JAK2)和磷酸化JAK2的蛋白水平。小鼠卵泡体外培养系统用于检测卵泡发育和排卵状况:结果:本研究发现,利拉鲁肽可抑制 PCOS 颗粒细胞中炎性因子的分泌,其中以 CXCL10 的抑制作用最为显著。此外,PCOS 患者颗粒细胞和卵泡液中的 CXCL10 明显高于非 PCOS 患者。我们应用体外卵泡培养等技术进行了机制探索,发现CXCL10在生理性排卵前破坏了卵母细胞与颗粒细胞之间的间隙连接蛋白α1(GJA1)的平衡,从而抑制了卵泡的发育和排卵。利拉鲁肽通过抑制JAK信号通路抑制了PCOS颗粒细胞中CXCL10的分泌,并能改善脱氢表雄酮(DHEA)诱导的卵泡发育障碍,补充CXCL10后可逆转这种障碍:本研究提示,利拉鲁肽通过JAK信号通路抑制颗粒细胞分泌CXCL10,从而改善生理排卵前卵母细胞与颗粒细胞间GJA1的平衡,最终改善多囊卵巢综合征的卵泡发育和排卵,为利拉鲁肽治疗多囊卵巢综合征排卵障碍的临床应用提供了更多支持性证据:试验注册:不适用。
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Liraglutide improves follicle development in polycystic ovary syndrome by inhibiting CXCL10 secretion.

Background: At present, a number of clinical trials have been carried out on GLP-1 receptor agonist liraglutide in the treatment of polycystic ovary syndrome (PCOS). However, the effect of liraglutide on follicle development and its specific mechanism are still unclear.

Methods: RNA sequencing was used to explore the molecular characteristics of granulosa cells from patients with PCOS treated with liraglutide. The levels of C-X-C motif chemokine ligand 10 (CXCL10) in follicular fluid were detected by ELISA, the expression levels of ovulation related genes and inflammatory factor genes in follicles and granulosa cells were detected by qPCR and the protein levels of connexin 43 (Cx43), Janus Kinase 2 (JAK2) and phosphorylated JAK2 were detected by Western blot. The mouse ovarian follicles culture system in vitro was used to detect the status of follicle development and ovulation.

Results: In the present study, we found that liraglutide inhibited the secretion of inflammatory factors in PCOS granulosa cells, among which CXCL10 was the most significant. In addition, CXCL10 was significantly higher in granulosa cells and follicular fluid in PCOS patients than in non-PCOS patients. We applied in vitro follicle culture and other techniques to carry out the mechanism exploration which revealed that CXCL10 disrupted the homeostasis of gap junction protein alpha 1 (GJA1) between oocyte and granulosa cells before physiological ovulation, thus inhibiting follicular development and ovulation. Liraglutide inhibited CXCL10 secretion in PCOS granulosa cells by inhibiting the JAK signaling pathway and can improved dehydroepiandrosterone (DHEA)-induced follicle development disorders, which is reversed by CXCL10 supplementation.

Conclusions: The present study suggests that liraglutide inhibits CXCL10 secretion in granulosa cells through JAK signaling pathway, thereby improving the homeostasis of GJA1 between oocyte and granulosa cells before physiological ovulation and ultimately improving the follicular development and ovulation of PCOS, which provides more supportive evidence for the clinical application of liraglutide in the treatment of ovulatory disorders in PCOS.

Trial registration: Not applicable.

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来源期刊
Reproductive Biology and Endocrinology
Reproductive Biology and Endocrinology 医学-内分泌学与代谢
CiteScore
7.90
自引率
2.30%
发文量
161
审稿时长
4-8 weeks
期刊介绍: Reproductive Biology and Endocrinology publishes and disseminates high-quality results from excellent research in the reproductive sciences. The journal publishes on topics covering gametogenesis, fertilization, early embryonic development, embryo-uterus interaction, reproductive development, pregnancy, uterine biology, endocrinology of reproduction, control of reproduction, reproductive immunology, neuroendocrinology, and veterinary and human reproductive medicine, including all vertebrate species.
期刊最新文献
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