Dimethyloxaloylglycine-preconditioned human umbilical cord mesenchymal stem cells protect against early pregnancy loss in mice

in Reproduction
Authors:
Anfeng Ning Reproductive and Genetic Center & NHC Key Laboratory of Reproductive Health Engineering Technology Research, National Research Institute for Family Planning (NRIFP), Beijing, China
Graduate Schools, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China

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https://orcid.org/0000-0002-3035-6513
,
Nansong Xiao Reproductive and Genetic Center & NHC Key Laboratory of Reproductive Health Engineering Technology Research, National Research Institute for Family Planning (NRIFP), Beijing, China
Graduate Schools, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China

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Xiaoqin Yu Reproductive and Genetic Center & NHC Key Laboratory of Reproductive Health Engineering Technology Research, National Research Institute for Family Planning (NRIFP), Beijing, China
Graduate Schools, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China

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Hu Wang Reproductive and Genetic Center & NHC Key Laboratory of Reproductive Health Engineering Technology Research, National Research Institute for Family Planning (NRIFP), Beijing, China
Graduate Schools, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China

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Chunyi Guan Reproductive and Genetic Center & NHC Key Laboratory of Reproductive Health Engineering Technology Research, National Research Institute for Family Planning (NRIFP), Beijing, China
Graduate Schools, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China

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Xu Ma Reproductive and Genetic Center & NHC Key Laboratory of Reproductive Health Engineering Technology Research, National Research Institute for Family Planning (NRIFP), Beijing, China
Graduate Schools, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China

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, and
Hong-Fei Xia Reproductive and Genetic Center & NHC Key Laboratory of Reproductive Health Engineering Technology Research, National Research Institute for Family Planning (NRIFP), Beijing, China
Graduate Schools, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China

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https://orcid.org/0000-0003-3305-9108

Correspondence should be addressed to X Ma: maxu_ky@nrifp.org.cn or to H-F X: hongfeixia@126.com

(A Ning and N Xiao contributed equally to this study)

DOI:
https://doi.org/10.1530/REP-24-0285
Volume/Issue:
Volume 169: Issue 5
Article ID:
e240285
Article Type:
Research Article
Online Publication Date:
16 Apr 2025
Copyright:
© the author(s) 2025
Restricted access
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In brief

Early pregnancy loss (EPL) is a common pregnancy problem lacking preventive measures. This study shows that DMOG-preconditioned hUC-MSCs can reduce early embryo loss.

Abstract

EPL, a common pregnancy complication, yet has few effective preventive measures currently. To investigate whether dimethyloxaloylglycine (DMOG)-preconditioned human umbilical cord mesenchymal stem cells (hUC-MSCs) can prevent EPL, we initially evaluated the effect of DMOG on hUC-MSCs in vitro. Subsequently, the DMOG-preconditioned hUC-MSCs were transplanted into the lipopolysaccharide (LPS)-induced murine abortion model for intervention, following which we conducted phenotypic analysis. It was found that DMOG treatment enhanced the mRNA expression of HIF1A, H19 and GLUT1 in hUC-MSCs and augmented their migration capability (P < 0.01). Co-culture experiments showed that DMOG-treated hUC-MSCs notably reduced the mRNA levels of IL6, IL1B and TNFA in LPS-induced HTR-8/SVneo cells (P < 0.01). Moreover, DMOG-preconditioned hUC-MSCs remarkably decreased the fetal resorption rate and increased the embryo weight in LPS-induced abortive mice (P < 0.01). Histological analysis indicated that DMOG-preconditioned hUC-MSCs more effectively promoted their homing and inhibited LPS-induced fibrosis at the maternal–fetal interface. Apart from suppressing inflammatory factors in the serum of pregnant mice, DMOG-preconditioned hUC-MSCs can downregulate the mRNA levels of Il2, Il1b, Tnfa, Il5 and Il9 (P < 0.01), which are pro-inflammatory cytokines secreted by M1 macrophages; and simultaneously upregulate the expression of Cd206 and Pparg (P < 0.01), which serve as the cell surface and nuclear receptors of M2 macrophages in the embryos. Immunofluorescence further verified that the transplantation of DMOG-preconditioned hUC-MSCs could increase the expression of CD206 in embryos. Therefore, DMOG-preconditioned hUC-MSCs might prevent EPL by promoting the transformation of M1 into M2 macrophages.

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Sept 2018 onwards Past Year Past 30 Days
Full Text Views 25 25 12
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Print ISSN:
1470-1626
Online ISSN:
1741-7899

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