Reproductive Medical Center, Department of Gynecology and Obstetrics, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
School of Chinese Medicine, Macau University of Science and Technology, Macau, China.
Reprod Sci. 2023 Jul;30(7):2263-2274. doi: 10.1007/s43032-022-01135-2. Epub 2023 Jan 23.
The present study aimed to determine the clinical predictive significance of HIF-1α in follicular development and assisted reproductive technology (ART). We collected follicular fluid (FF) and granulosa cells (GCs) from PCOS (polycystic ovary syndrome) patients (experimental group) and other patients who were infertile due to tubal factors or male factors (control group) with IVF/ICSI-ET. The localization and expression of HIF-1α in GCs were determined by immunofluorescence staining. HIF-1α protein and mRNA expression were detected by enzyme-linked immunosorbent assay and quantitative real-time PCR, respectively. To clarify the regulation of HIF-1α by TGF-β1, we added the HIF-1α-specific blocker YC-1 to GCs. The serum AMH, LH, LH/FSH, testosterone, BMI and the number of oocytes retrieved in the PCOS group were significantly higher, while the cleavage rate was significantly lower, than those in the control group. HIF-1α protein was expressed in the cytoplasm of GCs. The expression of HIF-1α protein in the FF of the PCOS group was significantly lower than that in the control group. However, the expression of HIF-1α protein in GCs between the two groups was not significantly different. HIF-1α protein was highly expressed in large FF (follicular diameter ≥ 14 mm). Compared with the control group, the expression of HIF-1α mRNA in GCs of the PCOS group was significantly lower. The results showed a significant positive correlation between HIF-1α and TGF-β1 expression. We found that both HIF-1α and TGF-β1 were involved in the development of PCOS follicular development. The mutual regulation of HIF-1α and TGF-β1 may be one of the important mechanisms of the occurrence and development of PCOS.
本研究旨在探讨 HIF-1α 在卵泡发育和辅助生殖技术（ART）中的临床预测意义。我们收集了多囊卵巢综合征（PCOS）患者（实验组）和因输卵管因素或男性因素导致不孕的其他患者（对照组）的卵泡液（FF）和颗粒细胞（GCs），这些患者均接受了 IVF/ICSI-ET。通过免疫荧光染色检测 GCs 中 HIF-1α 的定位和表达。通过酶联免疫吸附试验和实时定量 PCR 检测 HIF-1α 蛋白和 mRNA 的表达。为了阐明 TGF-β1 对 HIF-1α 的调节作用，我们向 GCs 中添加了 HIF-1α 特异性抑制剂 YC-1。与对照组相比，PCOS 组的血清 AMH、LH、LH/FSH、睾酮、BMI 和获得的卵母细胞数量明显更高，而卵裂率明显更低。HIF-1α 蛋白在 GCs 的细胞质中表达。PCOS 组 FF 中的 HIF-1α 蛋白表达明显低于对照组。然而，两组 GCs 之间 HIF-1α 蛋白的表达没有显著差异。HIF-1α 蛋白在大 FF（卵泡直径≥14mm）中高表达。与对照组相比，PCOS 组 GCs 中 HIF-1α mRNA 的表达明显降低。结果表明，HIF-1α 与 TGF-β1 表达之间存在显著正相关。我们发现 HIF-1α 和 TGF-β1 均参与了 PCOS 卵泡发育。HIF-1α 和 TGF-β1 的相互调节可能是 PCOS 发生和发展的重要机制之一。
