High levels of follicular fluid testosterone could impair oocyte developmental competency via affecting aryl hydrocarbon receptor pathway in PCOS patients

BMC Mol Cell Biol. 2022 Nov 11;23(1):47. doi: 10.1186/s12860-022-00449-y.

Abstract

Background: Although hormonal and metabolic dysfunction have been recognized as a possible cause of polycystic ovarian syndrome (PCOS), the associations between hyperandrogenism and aryl hydrocarbon receptor (Ahr) signaling pathway remains controversial. The current study aimed to investigate the effect of hyperandrogenism on oocyte developmental competency via regarding Ahr signaling downstream pathway in granulosa cells.

Materials and methods: Granulosa cells were collected from 45 PCOS patients under assisted reproductive technique (ART). Gene expression of Ahr downstream pathway was evaluated based on Reverse Transcription Q-PCR assay. Moreover the correlation was investigated between gene expression and hyperandrogenism, and oocyte developmental competency in PCOS.

Results: From the 45 PCOS patients, 26 (64.44%) had a high level of follicular fluid testosterone (FFT). Based on the FFT level, two groups of PCOS: HFT (high level of FFT) and non-HFT, were shown significant differences in oocyte and embryo quality, and fertilization and cleavage rates. Moreover, the mean relative expressions of Ahr and Arnt genes were significantly higher in HFT -PCOS group (p < 0.01 and p < 0.01) respectively. Also, the significant positive correlations were obtained for Ahr, Arnt, Cyp1A1, and Cyp1B1 with incidence of clinical hyperandrogenism and FFT level. Besides, our results showed that Ahr, Cyp1A1, and Cyp1B1 gene expression was correlated significantly with fertilization rate.

Conclusion: The present study suggested that hyperandrogenism could impair oocyte developmental competency via affecting Ahr signaling downstream pathway.

Keywords: Aryl Hydrocarbon Receptor; Gene Expression; Hyperandrogenism; Polycystic Ovary Syndrome.

MeSH terms

  • Cytochrome P-450 CYP1A1 / genetics
  • Cytochrome P-450 CYP1A1 / metabolism
  • Female
  • Follicular Fluid / metabolism
  • Humans
  • Hyperandrogenism* / metabolism
  • Oocytes / metabolism
  • Polycystic Ovary Syndrome* / genetics
  • Polycystic Ovary Syndrome* / metabolism
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / metabolism
  • Testosterone

Substances

  • Receptors, Aryl Hydrocarbon
  • Cytochrome P-450 CYP1A1
  • Testosterone