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. 2021 Dec 23;3:804921. doi: 10.3389/frph.2021.804921

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Copyright © 2021 Muter, Kong and Brosens.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Dynamic changes in cell states across the menstrual cycle. (A) Following menstruation, rapid re-epithelization of the endometrium may involve mesenchymal-epithelial transition (MET), proliferation of epithelial progenitors from unshed areas, or both. Positional oestrogen-dependent proliferation, reflecting an IFN-γ gradient generated by lymphoid aggregates residing in the endometrial-myometrial junction, imposes various levels of replication stress on individual cells during the follicular phase, which in turn drives the divergence in cell states upon decidualization. (B) Upper panel: In a non-conception cycle, falling progesterone levels promote senDeC/transDeC dominance and bystander senescence via prolonged SASP secretion, resulting in leukocyte recruitment and menstrual breakdown. Lower panel: Upon successful embryo implantation, progesterone-dependent DeC cells control rapid clearance of senDeC by recruiting and activating uNK cells.