The relationship between CYP19A1 gene expression in luteinized granulosa cells and follicular estradiol output in women with endometriosis

Endometriosis was claimed to negatively affect the intrafollicular environment, hindering oocyte competence. Previous studies evaluated expression levels of cytochrome P450 aromatase (CYP19A) in granulosa and cumulus oophorus cells collected from endometriosis women, but results are controversial. To further investigate the intrafollicular environment whose alteration may potentially disturb ovarian steroidogenesis in endometriosis, gene expression of CYP19A and of its upstream enzymes, StAR and 3 beta HSD was assessed in luteinized granulosa cells isolated from follicular fluids (FF) collected during Assisted Reproduction Technology (ART) procedures in women with stage III-IV disease and from subjects without the condition. In a subgroup of patients, cumulus oophorus cells (COCs) were also assessed for CYP19A, StAR and 3 beta HSD gene expression. No difference in mRNA expression of CYP19A1, StAR and 3 beta HSD in both granulosa cells and COCs was observed between the two groups of patients. No significant difference was also found between estradiol FF levels detected in endometriosis patients (median=873, IQR=522-1221 ng/ml)) and control patients (median=878, IQR=609-1137 ng/ml). To gain more insight into the intrafollicular regulation of CYP19A in patients with endometriosis, associations between expression of the analyzed genes, systemic and follicular 17 beta-estradiol levels and ART outcomes were assessed. While in the control group, levels of CYP19A1, StAR and 3 beta HSD transcripts significantly correlated with follicular estradiol levels (adjusted R2 of 0.60), no significant association was detected in affected women (adjusted R2 of 0.23). After stratification of the populations based on the presence of the disease, CYP19A1 expression was shown to correlate with the number of oocytes retrieved [beta:-1.214;95%CI: -2.085 -(-0.343); p = 0.007] in the control group while this association was not present in patients with endometriosis [beta:-0.003; 95%CI:-0.468-0.461; p = 0.988)]. These results do not support data from the literature indicating a reduced aromatase expression in granulosa cells of affected women, but they highlight a potential subtle mechanism affecting the ovulation process in these women.