Expression and Clinical Significance of HIF-1α in Follicular Fluid and Granulosa Cells in Infertile PCOS Patients

Reprod Sci. 2023 Jul;30(7):2263-2274. doi: 10.1007/s43032-022-01135-2. Epub 2023 Jan 23.

Abstract

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.

Keywords: Assisted reproductive technology; Follicular development; Hypoxia-inducible factor-1α; Polycystic ovary syndrome; Transforming growth factor-β1.

MeSH terms

  • Clinical Relevance
  • Female
  • Follicular Fluid / metabolism
  • Granulosa Cells / metabolism
  • Humans
  • Infertility* / metabolism
  • Male
  • Polycystic Ovary Syndrome* / complications
  • Polycystic Ovary Syndrome* / genetics
  • Polycystic Ovary Syndrome* / metabolism
  • RNA, Messenger / metabolism
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Transforming Growth Factor beta1
  • RNA, Messenger