Abstract

BACKGROUND

Human endometrium remains a poorly understood tissue of the female reproductive tract. The superficial endometrial functionalis, the site of embryo implantation, is repeatedly shed with menstruation, and the stem cell-rich deeper basalis is postulated to be responsible for the regeneration of the functionalis. Two recent manuscripts have demonstrated the 3D architecture of endometrial glands. These manuscripts have challenged and replaced the prevailing concept that these glands end in blind pouches in the basalis layer that contain stem cells in crypts, as in the intestinal mucosa, providing a new paradigm for endometrial glandular anatomy. This necessitates re-evaluation of the available evidence on human endometrial regeneration in both health and disease in the context of this previously unknown endometrial glandular arrangement.

OBJECTIVE AND RATIONALE

The aim of this review is to determine if the recently discovered glandular arrangement provides plausible explanations for previously unanswered questions related to human endometrial biology. Specifically, it will focus on re-appraising the theories related to endometrial regeneration, location of stem/progenitor cells and endometrial pathologies in the context of this recently unravelled endometrial glandular organization.

SEARCH METHODS

An extensive literature search was conducted from inception to April 2021 using multiple databases, including PubMed/Web of Science/EMBASE/Scopus, to select studies using keywords applied to endometrial glandular anatomy and regeneration, and the references included in selected publications were also screened. All relevant publications were included.

OUTCOMES

The human endometrial glands have a unique and complex architecture; branched basalis glands proceed in a horizontal course adjacent to the myometrium, as opposed to the non-branching, vertically coiled functionalis glands, which run parallel to each other as is observed in intestinal crypts. This complex network of mycelium-like, interconnected basalis glands is demonstrated to contain endometrial epithelial stem cells giving rise to single, non-branching functionalis glands. Several previous studies that have tried to confirm the existence of epithelial stem cells have used methodologies that prevent sampling of the stem cell-rich basalis. More recent findings have provided insight into the efficient regeneration of the human endometrium, which is preferentially evolved in humans and menstruating upper-order primates.

WIDER IMPLICATIONS

The unique physiological organization of the human endometrial glandular element, its relevance to stem cell activity and scarless endometrial regeneration will inform reproductive biologists and clinicians to direct their future research to determine disease-specific alterations in glandular anatomy in a variety of endometrial pathological conditions.

中文翻译：

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人类子宫内膜腺体的新型微结构：对子宫内膜再生和病理的影响

摘要

背景

人类子宫内膜仍然是一个鲜为人知的女性生殖道组织。浅表的子宫内膜功能区，即胚胎着床的部位，随着月经反复脱落，而富含干细胞的深层基底被推测负责功能区的再生。最近的两份手稿展示了子宫内膜腺体的 3D 结构。这些手稿挑战并取代了流行的概念，即这些腺体在基底层的盲袋中结束，其中包含隐窝中的干细胞，如在肠粘膜中，为子宫内膜腺体解剖学提供了新的范例。这需要在这种以前未知的子宫内膜腺体排列的背景下，重新评估人类子宫内膜在健康和疾病方面再生的现有证据。

目标和理由

本综述的目的是确定最近发现的腺体排列是否为以前未回答的与人类子宫内膜生物学相关的问题提供了合理的解释。具体来说，它将重点重新评估与子宫内膜再生、干/祖细胞位置和子宫内膜病理相关的理论，以在这个最近解开的子宫内膜腺体组织的背景下进行。

搜索方法

从开始到 2021 年 4 月，使用多个数据库（包括 PubMed/Web of Science/EMBASE/Scopus）进行了广泛的文献搜索，以选择使用应用于子宫内膜腺体解剖和再生的关键字的研究，并筛选了所选出版物中包含的参考文献。包括所有相关出版物。

结果

人类子宫内膜腺体具有独特而复杂的结构；与在肠隐窝中观察到的不分枝、垂直盘绕的功能性腺体相反，分支的基底腺在与子宫肌层相邻的水平过程中进行。这种由类似菌丝体的、相互连接的基底腺组成的复杂网络被证明含有子宫内膜上皮干细胞，从而产生单一的、非分支的功能性腺体。之前的几项试图证实上皮干细胞存在的研究使用了阻止对富含干细胞的基底进行取样的方法。最近的研究结果为人类子宫内膜的有效再生提供了见解，子宫内膜优先在人类和经期的高阶灵长类动物中进化。

更广泛的影响

人类子宫内膜腺元素的独特生理组织、其与干细胞活性和无疤痕子宫内膜再生的相关性将告知生殖生物学家和临床医生指导他们未来的研究，以确定各种子宫内膜病理条件下腺体解剖结构的疾病特异性改变。