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生长激素通过抑制 Fos 和 Jun 信号的激活,改善与年龄相关的卵巢储备耗竭和卵母细胞质量下降。

Growth hormone ameliorates the age-associated depletion of ovarian reserve and decline of oocyte quality via inhibiting the activation of Fos and Jun signaling.

机构信息

Reproductive Medicine Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, People's Republic of China.

Center for Clinical Stem Cell Reasearch, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, People's Republic of China.

出版信息

Aging (Albany NY). 2021 Feb 17;13(5):6765-6781. doi: 10.18632/aging.202534.

Abstract

Oocyte quality typically begins to decline with aging, which contributes to subfertility and infertility. However, there is still no effective treatment to restore the ovarian reserve and improve aged-oocyte quality. According to the present study, growth hormone (GH) secretion changes with maternal age in female mice. After intraperitoneal injection with GH (1 mg/kg body weight) every two days for two months, the 10-month-old mice showed a better ovarian reserve and oocyte quality than control mice. GH treatment decreased the occurrence rate of aneuploidy caused by spindle/chromosome defects. Additionally, the single oocyte transcriptome analysis indicated that GH decreased the expression of apoptosis-related genes in oocytes. It was also observed that GH treatment reduced the expression of γH2AX and apoptosis of aged oocytes via decreasing the activation of Fos and Jun. Collectively, our results indicate that GH treatment is an effective way to reverse the age-associated depletion of ovarian reserve and the decline of oocyte quality by decreasing apoptosis.

摘要

卵母细胞质量通常随着年龄的增长而下降,这导致了生育力下降和不孕。然而,目前仍然没有有效的治疗方法来恢复卵巢储备和改善老化卵母细胞的质量。根据本研究,生长激素(GH)在雌性小鼠中的分泌随母体年龄而变化。经过两个月,每隔两天腹腔注射 GH(1mg/kg 体重)后,10 月龄的小鼠表现出更好的卵巢储备和卵母细胞质量,而对照组小鼠则没有。GH 治疗降低了由纺锤体/染色体缺陷引起的非整倍体发生率。此外,单个卵母细胞转录组分析表明,GH 通过降低 Fos 和 Jun 的激活来降低卵母细胞中与凋亡相关的基因表达。还观察到,通过降低 γH2AX 的表达和衰老卵母细胞的凋亡,GH 治疗减少了卵母细胞中 γH2AX 的表达和凋亡。总的来说,我们的研究结果表明,GH 治疗是一种通过减少凋亡来逆转与年龄相关的卵巢储备耗竭和卵母细胞质量下降的有效方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/700d/7993724/d2e0fdff51e0/aging-13-202534-g001.jpg

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