Endometriomas are heterogeneous for functional FSH receptor expression and steroidogenic function

Area of Science:

• Reproductive Endocrinology
• Molecular Biology
• Gynecologic Pathology

Background:

• Ovarian endometriomas are common gynecologic lesions.
• The role of follicle-stimulating hormone (FSH) in endometrioma pathogenesis is not fully understood.
• FSH signaling may influence steroidogenesis within endometriomas.

Purpose of the Study:

• To investigate the expression and functionality of FSH receptors (FSHR) in ovarian endometriomas.
• To assess the response of endometriomas to FSH, specifically regarding aromatase and steroid hormone production.
• To characterize the heterogeneity of FSHR and steroidogenic pathways in endometriomas.

Main Methods:

• Analysis of endometrioma cyst capsules from 18 patients.
• Quantitative real-time PCR (qRT-PCR), immunoblotting, and immunohistochemistry for FSHR and steroidogenic enzymes.
• Explant cultures treated with FSH to measure CYP19A1 (aromatase) transcript variants and hormone output (estradiol, progesterone).

Main Results:

• FSHR transcripts were detected in all endometriomas, but protein levels were low and variable, showing mRNA-protein uncoupling.
• FSH stimulation did not uniformly induce aromatase transcript variants or consistently increase estradiol production.
• Significant inter-patient heterogeneity was observed in steroidogenic enzyme expression (StAR, CYP11A1, 3β-HSD, 17β-HSD) and hormone output.

Conclusions:

• Ovarian endometriomas display significant heterogeneity in functional FSHR expression and steroidogenic capacity.
• FSH responsiveness in endometriomas is variable, with inconsistent activation of aromatase pathways and hormone production.
• This heterogeneity may contribute to the variable clinical behavior of endometriomas, particularly during ovarian stimulation.