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2 February 2022 SIRT1 plays an important role in implantation and decidualization during mouse early pregnancy
Yeon Jeong Hwang, Gi-Jun Sung, Ryan Marquardt, Steven L. Young, Bruce A. Lessey, Tae Hoon Kim, Yong-Pil Cheon, Jae-Wook Jeong
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Abstract

Sirtuin 1 (SIRT1) is a member of the sirtuin family that functions to deacetylate both histones and non-histone proteins. Previous studies have identified significant SIRT1 upregulation in eutopic endometrium from infertile women with endometriosis. However, SIRT1 function in the uterus has not been directly studied. Using immunochemistry analysis, we found SIRT1 to be most strongly expressed at GD4.5 and GD5.5 in decidualized cells and at GD7.5 in secondary decidual cells in mouse. To assess the role of SIRT1 in uterine function, we generated uterine Sirt1 conditional knockout mice (Pgrcre/+Sirt1f/f; Sirt1d/d). A 6-month fertility trial revealed that Sirt1d/d females were subfertile. Implantation site numbers were significantly decreased in Sirt1d/d mice compared with controls at GD5.5. Sirt1d/d implantation sites at GD4.5 could be divided into two groups, Group #1 with luminal closure and nonspecific COX2 expression compared with controls (14/20) and Group #2 with an open lumen and no COX2 (6/20). In Sirt1d/d Group #1, nuclear FOXO1 expression in luminal epithelial cells was significantly decreased. In Sirt1d/d Group #2, nuclear FOXO1 expression was almost completely absent, and there was strong PGR expression in epithelial cells. At GD5.5, stromal PGR and COX2 were significantly decreased in Sirt1d/d uterine in the areas surrounding the embryo compared with controls, indicating defective decidualization. An artificially induced decidualization test revealed that Sirt1d/d females showed defects in decidualization response. All together, these data suggest that SIRT1 is important for decidualization and contributes to preparing a receptive endometrium for successful implantation.

© The Author(s) 2022. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Yeon Jeong Hwang, Gi-Jun Sung, Ryan Marquardt, Steven L. Young, Bruce A. Lessey, Tae Hoon Kim, Yong-Pil Cheon, and Jae-Wook Jeong "SIRT1 plays an important role in implantation and decidualization during mouse early pregnancy," Biology of Reproduction 106(6), 1072-1082, (2 February 2022). https://doi.org/10.1093/biolre/ioac026
Received: 26 September 2021; Accepted: 28 January 2022; Published: 2 February 2022
JOURNAL ARTICLE
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KEYWORDS
implantation
progesterone receptor
SIRT1
subfertility
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