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.

IF 0.9 4区医学 Q4 MEDICINE, RESEARCH & EXPERIMENTAL

Bulletin of Experimental Biology and Medicine Pub Date : 2025-04-01 Epub Date: 2025-05-31 DOI:10.1007/s10517-025-06417-8

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

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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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在年轻献血者卵泡液细胞外泡的影响下，高龄产妇积云细胞基因转录的变化

尝试使用从年轻捐赠者的卵泡液（FF）中分离的细胞外囊泡（EV）来恢复高龄产妇（AMA）的积云细胞（CCs）。FF样本取自抗逆转录病毒治疗期间23-26岁的健康女性。高龄产妇（36-47岁）的cc与年轻献血者的EV共培养。根据靶基因在CC和早期胚胎发生中的功能选择靶基因（PFKP、EREG、UBE2T、HAS2、VCAN、CYP19A、GREM1、STS、BAX、PTGS2、BCL2、SPSB2、AREG、CCNB1、EGFR）。根据最终卵泡成熟药物（hCG或促性腺激素释放激素激动剂，GnRHa）的类型对所有未分层的妇女进行比较分析，结果显示所选基因的表达无统计学差异。GnRHa组与年轻供体FF ev共培养后，cc中HAS2（增加1.8倍，p = 0.04）、GREM1（增加1.4倍，p = 0.08）、BAX（增加1.4倍，p = 0.04）的表达均有统计学意义。研究结果表明，当aGnRH与年轻女性的FF ev联合使用时，高龄产妇CC的“年轻化”潜力，因为在CC与FF ev共培养过程中，凋亡基因的表达减少，细胞增殖基因的表达增加。

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来源期刊

Bulletin of Experimental Biology and Medicine 医学-医学：研究与实验

CiteScore

1.50

自引率

14.30%

发文量

265

审稿时长

2 months

期刊介绍： Bulletin of Experimental Biology and Medicine presents original peer reviewed research papers and brief reports on priority new research results in physiology, biochemistry, biophysics, pharmacology, immunology, microbiology, genetics, oncology, etc. Novel trends in science are covered in new sections of the journal - Biogerontology and Human Ecology - that first appeared in 2005. World scientific interest in stem cells prompted inclusion into Bulletin of Experimental Biology and Medicine a quarterly scientific journal Cell Technologies in Biology and Medicine (a new Russian Academy of Medical Sciences publication since 2005). It publishes only original papers from the leading research institutions on molecular biology of stem and progenitor cells, stem cell as the basis of gene therapy, molecular language of cell-to-cell communication, cytokines, chemokines, growth and other factors, pilot projects on clinical use of stem and progenitor cells. The Russian Volume Year is published in English from April.