Transcriptomic analysis of cumulus cells shows altered pathways in patients with minimal and mild endometriosis.

Endometriosis is a chronic inflammatory disorder that is highly associated with infertility. This association seems to be related to oocyte impairment, mainly in the initial stages of endometriosis (minimal and mild), where no distortions or adhesions are present. Nonetheless, invasive oocyte analyses are not routinely feasible; thus, indirect assessment of oocyte quality is highly desirable, and, in this context, cumulus cells (CCs) may be more suitable targets of analysis. CCs are crucial in oocyte development and could be used as an index of oocyte quality. Therefore, this prospective case-control study aimed to shed light on the infertility mechanisms of endometriosis I/II by analyzing the CCs' mRNA transcription profile (women with endometriosis I/II, n = 9) compared to controls (women with tubal abnormalities or male factor, n = 9). The transcriptomic analyses of CCs from patients with minimal and mild endometriosis revealed 26 differentially expressed genes compared to the controls. The enrichment analysis evidenced some altered molecular processes: Cytokine-cytokine receptor interactions, Chemokine signaling, TNF signaling, NOD-like receptor signaling, NF-kappa B signaling, and inflammatory response. With the exception of CXCL12, all enriched genes were downregulated in CCs from patients with endometriosis. These findings provide a significant achievement in the field of reproductive biology, directing future studies to discover biomarkers of oocyte quality in endometriosis.

miR-532-3p: a possible altered miRNA in cumulus cells of infertile women with advanced endometriosis.

RESEARCH QUESTION: Is the profile of microRNA (miRNA) altered in cumulus cells of infertile women with early (EI/II) and advanced (EIII/IV) endometriosis? DESIGN: In this prospective case-control study, a miRNA profile including 754 targets was evaluated in samples of cumulus cells from infertile women with endometriosis (5 EI/II, 5 EIII/IV) and infertile controls (5, male and/or tubal factor) undergoing ovarian stimulation for intracytoplasmic sperm injection, using TaqMan® Array Human MicroRNA Cards A and B. The groups were compared with Kruskal-Wallis test, followed by Benjamini-Hochberg correction and Dunn's post hoc test. An in silico enrichment analysis was performed to list the possibly altered pathways in which the altered miRNA target genes are involved. RESULTS: Only the miRNA miR-532-3p showed significant differences among the analysed groups, being down-regulated in the EIII/IV group compared with the infertile control group, as well as compared with the EI/II group. The enrichment analysis showed that some genes regulated by this miRNA are involved in important pathways for the acquisition of oocyte competence, such as the oxytocin, calcium, Wnt, FoxO, ErbB and Ras signalling pathways, as well as the oocyte meiosis pathway. CONCLUSION: The present findings bring new perspectives to understanding the follicular microenvironment of infertile women with different stages of endometriosis. It is suggested that the dysregulation of miR-532-3p may be a potential mechanism involved in the aetiopathogenesis of endometriosis-related infertility. Further studies are needed to evaluate these pathways in cumulus cells of infertile women with the disease, as well as their impact on the acquisition of oocyte competence.