Changes in Gene Transcription in Cumulus Cells from Women of Advanced Maternal Age under the Influence of Extracellular Vesicles from Follicular Fluid of Young Donors.

An attempt was made to rejuvenate cumulus cells (CCs) of women of advanced maternal age (AMA) using extracellular vesicles (EV) isolated from the follicular fluid (FF) of young donors. FF samples were taken from healthy women aged 23-26 during the ART program. CCs from patients of advanced maternal age (36-47 years) were co-cultured with EV of young donors. The target genes were selected based on their functions in CC and early embryogenesis (PFKP, EREG, UBE2T, HAS2, VCAN, CYP19A, GREM1, STS, BAX, PTGS2, BCL2, SPSB2, AREG, CCNB1, EGFR). Comparative analysis of all women without stratification by the type of final follicle maturation drug (hCG or gonadotropin-releasing hormone agonist, GnRHa) revealed no statistically significant difference in the expression of the selected genes. In the group treated with GnRHa, a statistically significant increase in the expression of HAS2 (by 1.8 times, p = 0.04), GREM1 (by 1.4 times, p = 0.08), and BAX (by 1.4 times, p = 0.04) in CCs was observed after their co-culturing with FF EVs from young donors. The findings suggest the potential for the "rejuvenation" of CC in women of advanced maternal age when aGnRH is used in combination with FF EVs from young women, because the expression of apoptosis genes decreases and the expression cell proliferation gene increases during co-culturing of CC with FF EVs.