eLife:研究确定了健康子宫发育所需的细胞

2019-08-07 佚名 细胞

了解子宫发育的生物学过程对了解子宫健康和生育能力非常重要。由马萨诸塞州总医院(MGH)的研究人员领导的一个研究小组发现了一种细胞类型的新功能,这种细胞对子宫功能的形成至关重要。

了解子宫发育的生物学过程对了解子宫健康和生育能力非常重要。由马萨诸塞州总医院(MGH)的研究人员领导的一个研究小组发现了一种细胞类型的新功能,这种细胞对子宫功能的形成至关重要。

这些细胞是通过表达Misr2+来定义的,Misr2+是缪勒管抑制物质(MIS)的受体,由男性胚胎的睾丸分泌,以阻止产生女性生殖器官的结构的成熟。

尽管Misr2+细胞会抑制男性子宫的形成并不奇怪,但研究人员发现,这些细胞也会积极参与女性子宫的形成。研究结果发表在《eLife》杂志上。

"在没有MIS的情况下,女性生殖看门细胞的命运是未知的,"资深作者David Pepin博士说,他是MGH的分子生物学家助理和哈佛医学院的外科助理教授。"在这项研究中,我们发现,在小鼠、大鼠和人类的性分化时期过后,女性细胞继续表达MIS受体。此外,我们还发现,在啮齿类动物中,即使在出生后,这些细胞对MIS仍保持着敏感性。"

在出生后的第一周用MIS治疗啮齿动物,会干扰子宫的发育,导致日后不孕。Pepin说:"研究结果表明,哺乳动物对性分化信号的反应周期可能不像之前认为的那样受到限制。"

为了揭示更多细节,科学家们分析了MIS治疗后新生啮齿动物子宫内的细胞,发现子宫内膜缺乏某些关键细胞类型。研究人员怀疑,Misr2+细胞通常发展成这些细胞类型,但在暴露于MIS时被阻断。

该研究的第一作者Hatice Duygu Saatcioglu说:"如果没有这些细胞,大量的重要信号就会被破坏,导致子宫发育异常。这段时期对子宫层的规格非常关键,出生后几天就暴露在MIS环境中,会导致日后无法恢复的不孕,因为成人的子宫很薄,几乎完全由子宫肌层构成。"

Patricia K. Donahoe博士是MGH儿童医院 (Mass General Hospital for Children, MGHfC)外科研究实验室的联合作者和主任。她本人长期从事MIS功能的研究。她表示:"找到带有Misr2标记的细胞,可以进一步研究这些细胞是如何参与导致不孕的子宫病理过程。"

相反,这项研究的一些与MIS相关的发现也可能与男性有关,包括那些患有一种罕见的称为持续性穆勒管综合征的疾病的男性,在这种疾病中,子宫等组织可能由于MIS或其受体的突变而部分保留下来。

原始出处:
Saatcioglu HD1,2, Kano M1,2, Horn H1,2,3, et al.Single-cell sequencing of neonatal uterus reveals an Misr2+ endometrial progenitor indispensable for fertility.Elife. 2019 Jun 24;8. pii: e46349. doi: 10.7554/eLife.46349.

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    2019-11-18 clmlylxy
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    2020-02-12 膀胱癌
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    2019-08-09 neurowu
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    2019-08-07 医者仁心5538

    学习了

    0