排卵时颗粒细胞的新陈代谢与卵母细胞的能力有关,而肥胖和衰老会破坏这种新陈代谢。

IF 6 1区 医学 Q1 OBSTETRICS & GYNECOLOGY
Atsushi Morimoto, Ryan D Rose, Kirsten M Smith, Doan T Dinh, Takashi Umehara, Yasmyn E Winstanley, Hiroaki Shibahara, Darryl L Russell, Rebecca L Robker
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引用次数: 0

摘要

研究问题:卵母细胞的发育能力是否与颗粒细胞(GC)代谢的变化有关?GC代谢受LH激增的调节,肥胖和生殖衰老会改变GC代谢,在女性中,特定的代谢特征与受精失败或囊胚发育增加有关:卵母细胞成熟的细胞环境对其未来的发育能力至关重要。新陈代谢正在成为一个潜在的重要因素;然而,在正常的体内排卵条件下,GCs 和积层细胞之间的相对能量生产概况及其对不同底物的使用情况尚不十分清楚:本研究利用小鼠模型和接受促性腺激素诱导的卵母细胞抽吸术(IVF/ICSI)的妇女的卵母细胞,确定了卵母细胞对LH激增的代谢和底物利用情况:为了全面评估卵泡的能量代谢,我们使用实时代谢分析仪(Seahorse XFe96)绘制了小鼠GC和卵泡-卵母细胞复合体(COC)在排卵前的详细时间过程中的能量代谢动态图(线粒体呼吸、糖酵解和脂肪酸氧化)。与此同时,我们还测量了85名接受体外受精/卵胞浆内单精子显微注射(IVF/ICSI)的妇女(卵巢功能正常者21人;卵巢性不孕者64人)的GCs代谢概况,并将其与临床参数和周期结果联系起来:我们的研究揭示了GC能量代谢在排卵LH作用下的动态变化,线粒体呼吸和糖酵解受肥胖和衰老的影响不同,在小鼠和女性中均是如此。GC 的高呼吸与受精失败有关(P 限制、谨慎的原因:在将与卵母细胞质量呈正相关和负相关的代谢标志物用于临床预测胚胎结果之前,需要进行更大规模的前瞻性研究:这项研究为了解GC代谢对胚胎后续发育的重要性提供了新的视角,并强调了以优化线粒体代谢为重点的治疗策略的潜力,以支持胚胎发育:国家健康与医学研究委员会(澳大利亚)。作者无竞争利益。试验注册号:N/A:不适用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Granulosa cell metabolism at ovulation correlates with oocyte competence and is disrupted by obesity and aging.

Study question: Is oocyte developmental competence associated with changes in granulosa cell (GC) metabolism?

Summary answer: GC metabolism is regulated by the LH surge, altered by obesity and reproductive aging, and, in women, specific metabolic profiles are associated with failed fertilization versus increased blastocyst development.

What is known already: The cellular environment in which an oocyte matures is critical to its future developmental competence. Metabolism is emerging as a potentially important factor; however, relative energy production profiles between GCs and cumulus cells and their use of differential substrates under normal in vivo ovulatory conditions are not well understood.

Study design, size, duration: This study identified metabolic and substrate utilization profiles within ovarian cells in response to the LH surge, using mouse models and GCs of women undergoing gonadotropin-induced oocyte aspiration followed by IVF/ICSI.

Participants/materials, setting, methods: To comprehensively assess follicular energy metabolism, we used real-time metabolic analysis (Seahorse XFe96) to map energy metabolism dynamics (mitochondrial respiration, glycolysis, and fatty acid oxidation) in mouse GCs and cumulus-oocyte complexes (COCs) across a detailed time course in the lead up to ovulation. In parallel, the metabolic profile of GCs was measured in a cohort of 85 women undergoing IVF/ICSI (n = 21 with normal ovarian function; n = 64 with ovarian infertility) and correlated with clinical parameters and cycle outcomes.

Main results and the role of chance: Our study reveals dynamic changes in GC energy metabolism in response to ovulatory LH, with mitochondrial respiration and glycolysis differentially affected by obesity versus aging, in both mice and women. High respiration in GCs is associated with failed fertilization (P < 0.05) in a subset of women, while glycolytic reserve and mitochondrial ATP production are correlated with on-time development at Day 3 (P < 0.05) and blastocyst formation (P < 0.01) respectively. These data provide new insights into the cellular mechanisms of infertility, by uncovering significant associations between metabolism within the ovarian follicle and oocyte developmental competence.

Limitations, reasons for caution: A larger prospective study is needed before the metabolic markers that were positively and negatively associated with oocyte quality can be used clinically to predict embryo outcomes.

Wider implications of the findings: This study offers new insights into the importance of GC metabolism for subsequent embryonic development and highlights the potential for therapeutic strategies focused on optimizing mitochondrial metabolism to support embryonic development.

Study funding/competing interest(s): National Health and Medical Research Council (Australia). The authors have no competing interests.

Trial registration number: N/A.

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来源期刊
Human reproduction
Human reproduction 医学-妇产科学
CiteScore
10.90
自引率
6.60%
发文量
1369
审稿时长
1 months
期刊介绍: Human Reproduction features full-length, peer-reviewed papers reporting original research, concise clinical case reports, as well as opinions and debates on topical issues. Papers published cover the clinical science and medical aspects of reproductive physiology, pathology and endocrinology; including andrology, gonad function, gametogenesis, fertilization, embryo development, implantation, early pregnancy, genetics, genetic diagnosis, oncology, infectious disease, surgery, contraception, infertility treatment, psychology, ethics and social issues.
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