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RESEARCH PAPER / 2025-05-31

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.

B V Zingerenko, O V Burmenskaya, A P Sysoeva, J A Shevtsova, D N Silachev, N P Makarova, E A Kalinina

Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation, Moscow, Russia.Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation, Moscow, Russia. · pubmed

Abstract

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.

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Research summary

The paper claims that co-culturing cumulus cells from women of advanced maternal age with extracellular vesicles from young donors can lead to increased expression of genes associated with cell proliferation and decreased expression of apoptosis genes. This research is relevant as it explores potential mechanisms for rejuvenating reproductive cells, which could contribute to understanding and addressing age-related declines in fertility and cellular function.

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