目的:接受生育力保存的青少年的卵丘细胞(CC)和卵泡液(FF)的分子特征是否与卵母细胞供体不同?
结论:卵母细胞周围的微环境,包括CC和FF,与卵母细胞供体相比,接受生育能力保存的青少年发生了变化。
背景:青少年在月经初潮后经历了一段时间的发育不良。最近的证据表明,这可能至少部分是由于卵母细胞非整倍性增加。哺乳动物的生殖幼年与次优卵母细胞质量有关。
■这是一项前瞻性队列研究。青少年(10-19岁,n=23)和卵母细胞供体(22-30岁,n=31)在2020年11月1日至2023年5月1日期间在单个中心进行卵巢刺激和卵母细胞提取的研究纳入本研究。
方法:患者人口统计,卵巢刺激,并收集所有参与者的卵母细胞提取结果.在青少年(10-19岁,n=19)和卵母细胞供体(22-30岁,n=19)使用批量RNA测序。FF细胞因子谱(10-19岁,n=18vs25-30岁,n=16)使用细胞因子阵列进行比较。
结果:RNA-seq分析显示,与卵母细胞供体相比,青少年的CCs中有581个差异表达基因,361个基因下调,220个基因上调。与细胞周期和细胞分裂相关的通路富集的基因(如GO:1903047,P=3.5×10-43;GO:0051983,P=4.1×10-30;GO:0000281,P=7.7×10-15;GO:0044839,P=5.3×10-13)显著下调,与卵母细胞供体相比,在青少年的CC中,富含参与细胞和囊泡组织的几种途径的基因(例如GO:0010256,P=1.2×10-8;GO:0051129,P=6.8×10-7;GO:0016050,P=7.4×10-7;GO:0051640,P=8.1×10-7)被上调。与卵母细胞供体相比,青少年FF中9种细胞因子的水平显着增加:IL-1α(2倍),IL-1β(1.7倍),I-309(2倍),IL-15(1.6倍),TARC(1.9倍),TPO(2.1倍),IGFBP-4(2倍),IL-12-p40(1.7倍),和ENA-78(1.4倍)。有趣的是,这些细胞因子中的七种具有已知的促炎作用。重要的是,在患有或不患有癌症的青少年中,CC转录组和FF细胞因子谱均无差异.
方法:原始高通量测序数据已保存在基因表达综合(GEO)数据库中,登录号为GSE265995。
结论:本研究旨在通过研究即时卵母细胞微环境来获得相关配子质量的见解。由于样本稀缺,直接研究卵母细胞更具挑战性,因为它们被冷冻保存以备将来使用,但可以更准确地评估卵母细胞的生殖潜力。
结论:我们的研究结果对青少年生育力保持周期具有重要意义。了解该年龄组冷冻保存卵子的预期质量将为这些患者提供更好的生殖潜力咨询,并可能有助于确定建议库存的卵子数量,以实现未来活产的合理机会。
背景:该项目得到了普伦蒂斯之友组织SP0061324(M.M.L.和E.B.)的支持,Gesualdo家庭基金会(研究学者:M.M.L.),和NIH/NICHDK12HD050121(E.B.)。作者宣称不存在利益冲突。
OBJECTIVE: Do the molecular signatures of cumulus cells (CCs) and follicular fluid (FF) of adolescents undergoing fertility preservation differ from that of oocyte donors?
CONCLUSIONS: The microenvironment immediately surrounding the oocyte, including the CCs and FF, is altered in adolescents undergoing fertility preservation compared to oocyte donors.
BACKGROUND: Adolescents experience a period of subfecundity following menarche. Recent evidence suggests that this may be at least partially due to increased oocyte aneuploidy. Reproductive juvenescence in mammals is associated with suboptimal oocyte quality.
UNASSIGNED: This was a prospective cohort study. Adolescents (10-19 years old, n = 23) and oocyte donors (22-30 years old, n = 31) undergoing ovarian stimulation and oocyte retrieval at a single center between 1 November 2020 and 1 May 2023 were enrolled in this study.
METHODS: Patient demographics, ovarian stimulation, and oocyte retrieval outcomes were collected for all participants. The transcriptome of CCs associated with mature oocytes was compared between adolescents (10-19 years old, n = 19) and oocyte donors (22-30 years old, n = 19) using bulk RNA-sequencing. FF cytokine profiles (10-19 years old, n = 18 vs 25-30 years old, n = 16) were compared using cytokine arrays.
RESULTS: RNA-seq analysis revealed 581 differentially expressed genes in CCs of adolescents relative to oocyte donors, with 361 genes downregulated and 220 upregulated. Genes enriched in pathways involved in cell cycle and cell division (e.g. GO: 1903047, P = 3.5 × 10-43; GO: 0051983, P = 4.1 × 10-30; GO: 0000281, P = 7.7 × 10-15; GO: 0044839, P = 5.3 × 10-13) were significantly downregulated, while genes enriched in several pathways involved in cellular and vesicle organization (e.g. GO: 0010256, P = 1.2 × 10-8; GO: 0051129, P = 6.8 × 10-7; GO: 0016050, P = 7.4 × 10-7; GO: 0051640, P = 8.1 × 10-7) were upregulated in CCs of adolescents compared to oocyte donors. The levels of nine cytokines were significantly increased in FF of adolescents compared to oocyte donors: IL-1 alpha (2-fold), IL-1 beta (1.7-fold), I-309 (2-fold), IL-15 (1.6-fold), TARC (1.9-fold), TPO (2.1-fold), IGFBP-4 (2-fold), IL-12-p40 (1.7-fold), and ENA-78 (1.4-fold). Interestingly, seven of these cytokines have known pro-inflammatory roles. Importantly, neither the CC transcriptomes nor FF cytokine profiles were different in adolescents with or without cancer.
METHODS: Original high-throughput sequencing data have been deposited in Gene Expression Omnibus (GEO) database with the accession number GSE265995.
CONCLUSIONS: This study aims to gain insights into the associated gamete quality by studying the immediate oocyte microenvironment. The direct study of oocytes is more challenging due to sample scarcity, as they are cryopreserved for future use, but would provide a more accurate assessment of oocyte reproductive potential.
CONCLUSIONS: Our findings have implications for the adolescent fertility preservation cycles. Understanding the expected quality of cryopreserved eggs in this age group will lead to better counseling of these patients about their reproductive potential and may help to determine the number of eggs that is recommended to be banked to achieve a reasonable chance of future live birth(s).
BACKGROUND: This project was supported by Friends of Prentice organization SP0061324 (M.M.L. and E.B.), Gesualdo Family Foundation (Research Scholar: M.M.L.), and NIH/NICHD K12 HD050121 (E.B.). The authors have declared that no conflict of interest exists.