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细颗粒物 (PM) 通过其关键调节因子 SERPINB2 对人子宫内膜干细胞的各种有益功能的影响。

The impact of fine particulate matter (PM) on various beneficial functions of human endometrial stem cells through its key regulator SERPINB2.

机构信息

Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon, 21999, Republic of Korea.

Department of Molecular Medicine, School of Medicine, Gachon University, Incheon, 406-840, Republic of Korea.

出版信息

Exp Mol Med. 2021 Dec;53(12):1850-1865. doi: 10.1038/s12276-021-00713-9. Epub 2021 Dec 2.

Abstract

Fine particulate matter (PM) has a small diameter but a large surface area; thus, it may have broad toxic effects that subsequently damage many tissues of the human body. Interestingly, many studies have suggested that the recent decline in female fertility could be associated with increased PM exposure. However, the precise mechanisms underlying the negative effects of PM exposure on female fertility are still a matter of debate. A previous study demonstrated that resident stem cell deficiency limits the cyclic regenerative capacity of the endometrium and subsequently increases the pregnancy failure rate. Therefore, we hypothesized that PM exposure induces endometrial tissue damage and subsequently reduces the pregnancy rate by inhibiting various beneficial functions of local endometrial stem cells. Consistent with our hypothesis, we showed for the first time that PM exposure significantly inhibits various beneficial functions of endometrial stem cells, such as their self-renewal, transdifferentiation, and migratory capacities, in vitro and in vivo through the PM target gene SERPINB2, which has recently been shown to be involved in multiple stem cell functions. In addition, the PM-induced inhibitory effects on the beneficial functions of endometrial stem cells were significantly diminished by SERPINB2 depletion. Our findings may facilitate the development of promising therapeutic strategies for improving reproductive outcomes in infertile women.

摘要

细颗粒物(PM)直径小但表面积大;因此,它可能具有广泛的毒性作用,随后会损害人体的许多组织。有趣的是,许多研究表明,女性生育能力的近期下降可能与 PM 暴露的增加有关。然而,PM 暴露对女性生育力的负面影响的确切机制仍存在争议。先前的一项研究表明,驻留干细胞缺乏会限制子宫内膜的周期性再生能力,从而增加妊娠失败率。因此,我们假设 PM 暴露会导致子宫内膜组织损伤,并通过抑制局部子宫内膜干细胞的各种有益功能,进而降低妊娠率。与我们的假设一致,我们首次表明,PM 暴露通过最近被证明参与多种干细胞功能的 PM 靶基因 SERPINB2,显著抑制子宫内膜干细胞的各种有益功能,如自我更新、转分化和迁移能力,在体外和体内均如此。此外,SERPINB2 耗竭显著减弱了 PM 对子宫内膜干细胞有益功能的抑制作用。我们的发现可能有助于开发有前途的治疗策略,以改善不孕妇女的生殖结局。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f223/8741906/0bf92893bde0/12276_2021_713_Fig1_HTML.jpg

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