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双调蛋白对卵母细胞成熟和胚胎质量的影响:临床与分子视角的见解

Impact of Amphiregulin on Oocyte Maturation and Embryo Quality: Insights from Clinical and Molecular Perspectives.

作者信息

Kljajic Marija, Ney Jasmin Teresa, Wagenpfeil Gudrun, Baus Simona, Solomayer Erich-Franz, Kasoha Mariz

机构信息

Department of Gynecology, Obstetrics and Reproductive Medicine, Saarland University Hospital, Homburg, Saar, Germany.

Institute of Medical Biometry, Epidemiology and Medical Informatics, Saarland University, Homburg, Saar, Germany.

出版信息

Geburtshilfe Frauenheilkd. 2024 Sep 17;85(1):69-79. doi: 10.1055/a-2384-9193. eCollection 2025 Jan.

DOI:10.1055/a-2384-9193
PMID:39758117
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11695094/
Abstract

INTRODUCTION

Identifying non-invasive biomarkers which can predict the outcome of intracytoplasmic sperm injection (ICSI) is crucial, particularly in Germany where the challenges are intensified by the Embryo Protection Act. Recent research has highlighted biomarkers within the epidermal growth factor (EGF) family as central to follicular processes, although their predictive utility remains a subject of debate in the literature. Therefore, the primary objective of this study was to investigate the significance of amphiregulin concentrations in follicular fluid and gene expression in mural granulosa cells on oocyte maturation, fertilization, and embryo quality.

PATIENTS AND METHODS

A total of 33 women were recruited at the University Clinic of Saarland Fertility Center (Homburg, Germany). Follicular fluid aspiration consisted of single/individual aspiration of follicles, enabling a 1 : 1 correlation with retrieved oocytes. Follicular fluid and mural granulosa cell samples from 108 oocytes were analyzed. Amphiregulin levels were determined with enzyme-linked immunosorbent assay, while gene expression was analyzed with the StepOnePlus Real-Time PCR System using TaqMan Fast Advanced Master Mix assays.

RESULTS

Results showed that amphiregulin concentrations affect oocyte maturation, fertilization, and embryo quality, while luteinizing hormone concentrations influence oocyte maturation, with significant differences identified between fertilized/unfertilized and good/poor embryo groups. Amphiregulin expression significantly impacts oocyte maturation, with downregulation observed in immature oocytes, while luteinizing hormone/chorionic gonadotropin receptor expression showed no significant differences between groups and did not influence maturation, fertilization, or embryo quality.

CONCLUSION

These findings are very important for advancing infertility treatment, especially in Germany. The results for amphiregulin may provide prognostic insights which could be useful when selecting viable oocytes and embryos. This research underscores the importance of non-invasive biomarkers for optimizing ICSI outcomes and potentially enhancing the success rates of assisted reproductive technology.

摘要

引言

识别能够预测卵胞浆内单精子注射(ICSI)结果的非侵入性生物标志物至关重要,尤其是在德国,《胚胎保护法》加剧了这方面的挑战。近期研究强调表皮生长因子(EGF)家族中的生物标志物是卵泡发育过程的核心,尽管其预测效用在文献中仍是一个有争议的话题。因此,本研究的主要目的是探讨卵泡液中双调蛋白浓度及壁颗粒细胞中基因表达对卵母细胞成熟、受精和胚胎质量的意义。

患者与方法

在德国洪堡萨尔州立大学临床生育中心招募了33名女性。卵泡液抽吸包括对卵泡进行单次/个体抽吸,从而使抽取的卵泡液与回收的卵母细胞实现1:1对应。对来自108个卵母细胞的卵泡液和壁颗粒细胞样本进行了分析。采用酶联免疫吸附测定法测定双调蛋白水平,同时使用TaqMan Fast Advanced Master Mix检测法通过StepOnePlus实时PCR系统分析基因表达。

结果

结果显示,双调蛋白浓度影响卵母细胞成熟、受精和胚胎质量,而促黄体生成素浓度影响卵母细胞成熟,在受精/未受精以及优质/劣质胚胎组之间发现了显著差异。双调蛋白表达对卵母细胞成熟有显著影响,在未成熟卵母细胞中观察到表达下调,而促黄体生成素/绒毛膜促性腺激素受体表达在各组之间无显著差异,且不影响成熟、受精或胚胎质量。

结论

这些发现对于推进不孕症治疗非常重要,尤其是在德国。双调蛋白的结果可能提供预后见解,这在选择有活力的卵母细胞和胚胎时可能会很有用。本研究强调了非侵入性生物标志物对于优化ICSI结果以及潜在提高辅助生殖技术成功率的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cb7/11695094/034b694cbe62/10-1055-a-2384-9193_23851287.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cb7/11695094/5fd894f5440e/10-1055-a-2384-9193_23851284.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cb7/11695094/7a53bb87916b/10-1055-a-2384-9193_23851285.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cb7/11695094/0e7c628dcab8/10-1055-a-2384-9193_23851286.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cb7/11695094/034b694cbe62/10-1055-a-2384-9193_23851287.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cb7/11695094/5fd894f5440e/10-1055-a-2384-9193_23851284.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cb7/11695094/7a53bb87916b/10-1055-a-2384-9193_23851285.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cb7/11695094/0e7c628dcab8/10-1055-a-2384-9193_23851286.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cb7/11695094/034b694cbe62/10-1055-a-2384-9193_23851287.jpg

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Luteinizing hormone stimulates the expression of amphiregulin in human theca cells.促黄体生成素刺激人卵巢膜细胞中 Amphiregulin 的表达。
J Ovarian Res. 2022 Dec 7;15(1):129. doi: 10.1186/s13048-022-01062-5.
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Follicular fluid steroid and gonadotropic hormone levels and mitochondrial function from exosomes predict embryonic development.
卵泡液类固醇和促性腺激素水平以及外泌体中的线粒体功能可预测胚胎发育。
Front Endocrinol (Lausanne). 2022 Nov 9;13:1025523. doi: 10.3389/fendo.2022.1025523. eCollection 2022.
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Recombinant LH supplementation improves cumulative live birth rates in the GnRH antagonist protocol: a multicenter retrospective study using a propensity score-matching analysis.重组 LH 补充治疗改善 GnRH 拮抗剂方案中的累积活产率:一项采用倾向评分匹配分析的多中心回顾性研究。
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