P–293 Ovarian endometriomas are heterogenous for the steroidogenic function and the expression of estrogen and progesterone receptors

Abstract

Abstract Study question Do all ovarian endometriomas have steroidogenic function and express estrogen and progesterone receptors? Summary answer No, they are heterogenous for the steroidogenic function and the expression of the estrogen and progesterone receptors. What is known already Excessive ectopic estrogen production and up-regulation of estrogen receptor- β, which drives inflammation together with aberrant progesterone signaling leading to impaired decidualization and establishment of ectopic endometrial implants together with down-regulated progesterone receptor (PR) expression are the cardinal molecular features of the disease. However, several fundamental questions still remain to be answered as to whether all ovarian endometriomas carry these molecular aberrations and are steroidogenically active; and if so, the amount of sex steroids they produce correlate with the level of expression of steroidogenic enzymes. We aimed to address these questions in the current study. Study design, size, duration A molecular research study on the surgical specimens collected between April 2020 and December 2020. Seven histopathologically confirmed benign endometriotic cyst capsules obtained from the patients undergoing laparoscopic excision of unilateral ovarian endometriomas without deep infiltrating endometriosis during early follicular phase were used in the study. Participants/materials, setting, methods The mean age±SD (range) of the patients were 32.8±4.9 (30–39). The mean endometrioma size was 5±1.2cm (5–7.5 cm). The samples were cut into equal size pieces of 0.5x0.5cm size and cultured for one day to measure their E2and P4production; and analyzed for the expression of steroidogenic enzymes with quantitative immunoblotting and for the expression of FSH-R, ER and PR with real-time qRT-PCR methods. Luteinized granulosa cells and ovarian cortex were set as references. Main results and the role of chance StAR expression was consistently observed in all samples. However, we noticed significant discrepancies among the samples regarding their steroidogenic function and the expression of aromatase and 3 β-HSD enzymes. E2 production exhibited significant variation (from 5 to 1177pg/mL) from sample to sample despite comparable levels of aromatase expression. ER- βup-regulation as a cardinal molecular feature of endometriosis, was observed in all but one samples (1.46 to 5.48 folds, p < 0.0001). However, its expression level did not correlate with either aromatase expression or the amount of E2 the samples produced. A similar phenomenon was observed in P4 arm of steroidogenesis. Even though 3 β-HSD was expressed by all but one samples detectable amount of P4 was produced only by two samples (up to 15ng/mL). PR expression was down-regulated only in two samples (0.3 to 0.07 folds, p < 0.0001), and significantly up-regulated in the other samples (1.2 to 4.7 folds, p < 0.001). No correlation was found among the samples regarding the expression of PR, 3 β-HSD and P4 output. FSH-R was detected in all samples at the levels comparable to ovarian cortex but its expression level did not show any correlation with ER, aromatase expression and E2 production. Limitations, reasons for caution These results need to be confirmed in studies with larger sample size and different types of endometriotic lesions. Wider implications of the findings: The regulation of steroidogenic activity of endometriomas cannot simply be explained by the expression level of the steroidogenic enzymes, underscoring the importance of other mechanisms that post-translationally regulate their enzymatic activity and metabolism of estrogen and progesterone. PR is not always down-regulated and FSH-R is commonly up-regulated in ovarian endometriomas. Trial registration number Not applicable