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RGMc作为新基因配体在卵巢卵泡发育中的作用。

Role of RGMc as a Neogenin Ligand in Follicular Development in the Ovary.

作者信息

Kim Yu Jin, Park YoungJoon, Park Yeo Reum, Kim Young Sang, Lee Hye Ran, Lee Sang Jin, Kim Myung Joo, Kwack KyuBum, Ko Jung Jae, Lee Jae Ho

机构信息

CHA Fertility Center Seoul Station, Seoul 04637, Korea.

Department of Biomedical Science, CHA University, Gyeonggi-do, Seongnam 13488, Korea.

出版信息

Biomedicines. 2021 Mar 10;9(3):280. doi: 10.3390/biomedicines9030280.

DOI:10.3390/biomedicines9030280
PMID:33801938
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7999520/
Abstract

There is currently no cure for infertility in women with a poor ovarian response (POR). Neogenin is reported to be abundantly expressed in the ovary; however, its role in mammalian follicular development is unclear and its ligand and signaling pathway remain uncertain. We systematically investigated the role of neogenin and the ligand repulsive guidance molecule c (RGMc) during follicular development. We treated hyperstimulated mouse ovaries with RGMc and analyzed follicular development. Furthermore, we investigated clusters of up/downregulated genes in RGMc-treated ovaries using whole-transcriptome next-generation sequencing (NGS). In addition, we investigated whether expression of up/downregulated factors identified by NGS was also altered in cumulus cells (CCs) of patients with a POR. The number of oocytes was 40% higher in RGMc-treated ovaries than in control ovaries. NGS data indicated that prostaglandin D2 (PGD2) was involved in the RGMc signaling pathway during follicular development. RGMc treatment significantly elevated the PGD2 level in culture medium of CCs obtained from patients with a POR. Our results demonstrate that RGMc as neogenin ligand promotes follicular development in ovaries via the PGD2 signaling pathway. Therefore, it may be possible to use RGMc for ovarian stimulation in patients with a POR.

摘要

目前，对于卵巢反应不良（POR）的女性不孕症尚无治愈方法。据报道，Neogenin在卵巢中大量表达；然而，其在哺乳动物卵泡发育中的作用尚不清楚，其配体和信号通路也仍不明确。我们系统地研究了Neogenin和配体排斥导向分子c（RGMc）在卵泡发育过程中的作用。我们用RGMc处理超刺激的小鼠卵巢，并分析卵泡发育情况。此外，我们使用全转录组下一代测序（NGS）研究了RGMc处理的卵巢中上调/下调基因的簇。另外，我们研究了NGS鉴定出的上调/下调因子的表达在POR患者的卵丘细胞（CCs）中是否也发生了改变。RGMc处理的卵巢中的卵母细胞数量比对照卵巢中的高40%。NGS数据表明，前列腺素D2（PGD2）在卵泡发育过程中参与了RGMc信号通路。RGMc处理显著提高了从POR患者获得的CCs培养基中的PGD2水平。我们的结果表明，RGMc作为Neogenin配体通过PGD2信号通路促进卵巢中的卵泡发育。因此，有可能将RGMc用于POR患者的卵巢刺激。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f983/7999520/ddee1f15652b/biomedicines-09-00280-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f983/7999520/b7c7c843b93c/biomedicines-09-00280-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f983/7999520/52c32b0b2fa2/biomedicines-09-00280-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f983/7999520/5deb859e867e/biomedicines-09-00280-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f983/7999520/1b45a5e579fe/biomedicines-09-00280-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f983/7999520/fae060f1dfe2/biomedicines-09-00280-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f983/7999520/831069989033/biomedicines-09-00280-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f983/7999520/bfa891dba396/biomedicines-09-00280-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f983/7999520/ddee1f15652b/biomedicines-09-00280-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f983/7999520/b7c7c843b93c/biomedicines-09-00280-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f983/7999520/52c32b0b2fa2/biomedicines-09-00280-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f983/7999520/5deb859e867e/biomedicines-09-00280-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f983/7999520/1b45a5e579fe/biomedicines-09-00280-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f983/7999520/fae060f1dfe2/biomedicines-09-00280-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f983/7999520/831069989033/biomedicines-09-00280-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f983/7999520/bfa891dba396/biomedicines-09-00280-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f983/7999520/ddee1f15652b/biomedicines-09-00280-g008.jpg

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