Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, China.
Shanghai Ji Ai Genetics and IVF Institute, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.
Reprod Sci. 2023 Jul;30(7):2219-2230. doi: 10.1007/s43032-022-01147-y. Epub 2023 Jan 24.
Some studies have been conducted to explore the influence of growth hormone (GH) on oocytes in in vitro maturation (IVM); however, previous studies reporting showed different results, and the specific mechanisms were not clear. In the present study, GH supplementation improved oocyte maturation rate. The rate of germinal vesicle breakdown (GVBD) in the GH group was 83.9%, which was significantly higher than that (72.1%) in the control group (p = 0.001). The maturation rate of the GH group (79.2%) was significantly higher than that (65.4%) of the control group (p = 0.000). The fertilization (68.6 vs. 59.3%) and blastocyst (30 vs. 25.3%) rates showed an increasing trend in the GH group compared to those in controls. The dynamic parameters of nuclear maturation of oocytes were recorded by time-lapse monitoring system; oocytes in the GH group completed nuclear maturation earlier than did those in the control group. GH reduced cAMP levels to promote oocyte maturation. Single-cell RNA sequencing analysis revealed that the majority of differentially expressed genes (DEGs) involved in mitochondrial oxidative phosphorylation was upregulated in the GH group. Furthermore, the mitochondrial membrane potential of oocytes significantly increased, and the levels of intracellular reactive oxygen species (ROS) and Ca largely decreased in the GH group. Finally, single-oocyte transcriptome analysis indicated that GH decreased the expression of apoptosis-related genes in oocytes. GH treatment reduced the expression of γH2AX and caspase-3. Therefore, GH improves the developmental potential of immature oocytes by reducing cAMP levels more rapidly within 0.5 h, protecting mitochondrial function, and reducing DNA damage and apoptosis.
一些研究旨在探讨生长激素（GH）对体外成熟（IVM）卵母细胞的影响；然而，之前的研究结果显示出不同的结果，具体机制尚不清楚。本研究中，GH 补充剂提高了卵母细胞成熟率。GH 组的生发泡破裂（GVBD）率为 83.9%，明显高于对照组的 72.1%（p=0.001）。GH 组的成熟率（79.2%）明显高于对照组的（65.4%）（p=0.000）。GH 组的受精率（68.6%比 59.3%）和囊胚率（30%比 25.3%）呈上升趋势。通过时差监测系统记录卵母细胞核成熟的动态参数；GH 组的卵母细胞核成熟时间早于对照组。GH 通过降低 cAMP 水平促进卵母细胞成熟。单细胞 RNA 测序分析显示，GH 组中涉及线粒体氧化磷酸化的大多数差异表达基因（DEGs）上调。此外，GH 组卵母细胞的线粒体膜电位显著增加，细胞内活性氧（ROS）和 Ca 水平显著降低。最后，单细胞转录组分析表明，GH 降低了卵母细胞中凋亡相关基因的表达。GH 处理降低了卵母细胞中 γH2AX 和 caspase-3 的表达。因此，GH 通过在 0.5 h 内更迅速地降低 cAMP 水平，保护线粒体功能，减少 DNA 损伤和凋亡，从而提高未成熟卵母细胞的发育潜力。
