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养精种玉汤调控卵巢颗粒细胞线粒体动力学改善卵巢储备功能减退的机制研究。

Mechanism study of YangJing ZhongYu decoction on regulating mitochondrial dynamics of ovarian granular cells and improving diminished ovarian reserve.

机构信息

Department of Gynecology, The Second Affiliated Hospital of Hunan University of Chinese Medicine, 233 CAI 'e North Road, Kaifu District, Changsha, 410005, Hunan, China.

出版信息

J Ovarian Res. 2024 Sep 17;17(1):188. doi: 10.1186/s13048-024-01506-0.

DOI:10.1186/s13048-024-01506-0
PMID:39289738
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11406875/
Abstract

OBJECTIVE

Diminished ovarian reserve (DOR) encompasses both reproductive and endocrine disorders, resulting in a decline in female fertility. This paper explored the mechanism of Yangjing Zhongyu Decoction (YJZYD) regulating mitochondrial dynamics of ovarian granulosa cells (GCs) to improve DOR.

METHODS

DOR patients were treated with YJZYD, with ovarian volume (OV), antral follicle count (AFC), and endometrial thickness (EMT) detected. C57BL/6 female mice were treated by cyclophosphamide (Cy) intraperitoneal injection and YJZYD solution daily gavage, with serum anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels determined. Ovarian GCs (KGN) were interfered with 4-Hydroperoxy-Cyclophosphamide (4-HC) and treated with the MAPK/ERK pathway inhibitor or activator.

RESULTS

DOR patients showed increased levels of serum AMH, E2, OV, AFC and EMT, while reduced FSH and LH levels after YJZYD treatment. After Cy induction, DOR mice exhibited irregular estrous cycles, diminished serum AMH and E2 levels, elevated FSH and LH levels, reduced follicle number and atresia follicle number, disorderly arranged GCs, and severe interstitial fibrosis. After 4-HC treatment, KGN proliferation and Bcl-2, MFN1, and MFN2 were suppressed, while apoptotic rate, Bax, Cleaved-caspase-3, and p-Drp1 (Ser616) levels, and mitochondrial fission and quantity increased. YJZYD promoted 4-HC-treated KGN proliferation, boosted mitochondrial fusion, and inhibited apoptosis and mitochondrial fission via the MAPK/ERK pathway.

CONCLUSION

YJZYD promoted ovarian GC proliferation and mitochondrial fusion, suppressed cell apoptosis and mitochondrial fission, and effectively improved DOR in mice by activating the MAPK/ERK pathway, providing a theoretical basis for the clinical application value of YJZYD in DOR treatment.

摘要

目的

卵巢储备功能降低(DOR)包括生殖和内分泌紊乱,导致女性生育能力下降。本文探讨了养精种玉汤(YJZYD)调节卵巢颗粒细胞(GC)线粒体动力学以改善 DOR 的机制。

方法

DOR 患者接受 YJZYD 治疗,检测卵巢体积(OV)、窦卵泡计数(AFC)和子宫内膜厚度(EMT)。C57BL/6 雌性小鼠腹腔注射环磷酰胺(Cy)并每日灌胃 YJZYD 溶液,检测血清抗苗勒管激素(AMH)、卵泡刺激素(FSH)、黄体生成素(LH)和雌二醇(E2)水平。卵巢 GC(KGN)用 4-羟基环磷酰胺(4-HC)干扰,并用 MAPK/ERK 通路抑制剂或激活剂处理。

结果

DOR 患者接受 YJZYD 治疗后,血清 AMH、E2、OV、AFC 和 EMT 水平升高,而 FSH 和 LH 水平降低。Cy 诱导后,DOR 小鼠出现不规则发情周期,血清 AMH 和 E2 水平降低,FSH 和 LH 水平升高,卵泡数和闭锁卵泡数减少,GC 排列紊乱,间质纤维化严重。4-HC 处理后,KGN 增殖和 Bcl-2、MFN1 和 MFN2 受到抑制,而凋亡率、Bax、Cleaved-caspase-3 和 p-Drp1(Ser616)水平以及线粒体分裂和数量增加。YJZYD 通过 MAPK/ERK 通路促进 4-HC 处理的 KGN 增殖,促进线粒体融合,抑制细胞凋亡和线粒体分裂。

结论

YJZYD 通过激活 MAPK/ERK 通路促进卵巢 GC 增殖和线粒体融合,抑制细胞凋亡和线粒体分裂,有效改善小鼠 DOR,为 YJZYD 在 DOR 治疗中的临床应用价值提供理论依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d89a/11406875/570054175d25/13048_2024_1506_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d89a/11406875/ace6ad24b8e0/13048_2024_1506_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d89a/11406875/7c4410fe3713/13048_2024_1506_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d89a/11406875/bc1ea770eea9/13048_2024_1506_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d89a/11406875/477832ade77a/13048_2024_1506_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d89a/11406875/570054175d25/13048_2024_1506_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d89a/11406875/ace6ad24b8e0/13048_2024_1506_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d89a/11406875/7c4410fe3713/13048_2024_1506_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d89a/11406875/bc1ea770eea9/13048_2024_1506_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d89a/11406875/477832ade77a/13048_2024_1506_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d89a/11406875/570054175d25/13048_2024_1506_Fig5_HTML.jpg

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