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利用常规刺激周期中的人卵母细胞的卵巢支持细胞进行体外成熟挽救，可获得核成熟度提高且转录组与体内成熟卵母细胞相似的卵母细胞。

Rescue in vitro maturation using ovarian support cells of human oocytes from conventional stimulation cycles yields oocytes with improved nuclear maturation and transcriptomic resemblance to in vivo matured oocytes.

机构信息

Gameto Inc., 430 E. 29th St Fl 14, New York, NY, 10016, USA.

Obstetrics, Gynecology, and Reproductive Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

出版信息

J Assist Reprod Genet. 2024 Aug;41(8):2021-2036. doi: 10.1007/s10815-024-03143-4. Epub 2024 May 30.

DOI:10.1007/s10815-024-03143-4
PMID:38814543
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11339229/
Abstract

PURPOSE

Determine if the gene expression profiles of ovarian support cells (OSCs) and cumulus-free oocytes are bidirectionally influenced by co-culture during in vitro maturation (IVM).

METHODS

Fertility patients aged 25 to 45 years old undergoing conventional ovarian stimulation donated denuded immature oocytes for research. Oocytes were randomly allocated to either OSC-IVM culture (intervention) or Media-IVM culture (control) for 24-28 h. The OSC-IVM culture condition was composed of 100,000 OSCs in suspension culture with human chorionic gonadotropin (hCG), recombinant follicle stimulating hormone (rFSH), androstenedione, and doxycycline supplementation. The Media-IVM control lacked OSCs and contained the same supplementation. A limited set of in vivo matured MII oocytes were donated for comparative evaluation. Endpoints consisted of MII formation rate, morphological and spindle quality assessment, and gene expression analysis compared to in vitro and in vivo controls.

RESULTS

OSC-IVM resulted in a statistically significant improvement in MII formation rate compared to the Media-IVM control, with no apparent effect on morphology or spindle assembly. OSC-IVM MII oocytes displayed a closer transcriptomic maturity signature to IVF-MII controls than Media-IVM control MII oocytes. The gene expression profile of OSCs was modulated in the presence of oocytes, displaying culture- and time-dependent differential gene expression during IVM.

CONCLUSION

The OSC-IVM platform is a novel tool for rescue maturation of human oocytes, yielding oocytes with improved nuclear maturation and a closer transcriptomic resemblance to in vivo matured oocytes, indicating a potential enhancement in oocyte cytoplasmic maturation. These improvements on oocyte quality after OSC-IVM are possibly occurring through bidirectional crosstalk of cumulus-free oocytes and ovarian support cells.

摘要

目的

确定卵巢支持细胞（OSC）和无卵丘卵母细胞的基因表达谱是否在体外成熟（IVM）过程中通过共培养而双向影响。

方法

接受常规卵巢刺激的 25-45 岁的生育患者捐献裸化不成熟卵母细胞用于研究。将卵母细胞随机分配到 OSC-IVM 培养（干预）或 Media-IVM 培养（对照）中 24-28 小时。OSC-IVM 培养条件由悬浮培养的 100000 个 OSC 组成，补充人绒毛膜促性腺激素（hCG）、重组卵泡刺激素（rFSH）、雄烯二酮和强力霉素。Media-IVM 对照缺乏 OSCs，但含有相同的补充物。还捐赠了一组有限的体内成熟的 MII 卵母细胞进行比较评估。终点包括 MII 形成率、形态和纺锤体质量评估，以及与体内和体外对照相比的基因表达分析。

结果

与 Media-IVM 对照相比，OSC-IVM 导致 MII 形成率有统计学意义的提高，对形态或纺锤体组装没有明显影响。OSC-IVM MII 卵母细胞的转录组成熟特征与 IVF-MII 对照更接近，而 Media-IVM 对照 MII 卵母细胞则不然。在存在卵母细胞的情况下，OSC 的基因表达谱发生了调节，在 IVM 过程中表现出培养和时间依赖性的差异基因表达。

结论

OSC-IVM 平台是一种挽救人类卵母细胞成熟的新工具，可产生核成熟程度提高且与体内成熟卵母细胞转录组更相似的卵母细胞，表明卵母细胞细胞质成熟有潜在增强。在 OSC-IVM 后卵母细胞质量的这些改善可能是通过无卵丘卵母细胞和卵巢支持细胞的双向串扰发生的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/675a/11339229/9e04c327c3d2/10815_2024_3143_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/675a/11339229/d1b446675605/10815_2024_3143_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/675a/11339229/3ea0679b9e22/10815_2024_3143_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/675a/11339229/6b46af6ea8b9/10815_2024_3143_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/675a/11339229/9e04c327c3d2/10815_2024_3143_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/675a/11339229/d1b446675605/10815_2024_3143_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/675a/11339229/3ea0679b9e22/10815_2024_3143_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/675a/11339229/6b46af6ea8b9/10815_2024_3143_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/675a/11339229/9e04c327c3d2/10815_2024_3143_Fig4_HTML.jpg

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