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MUC16 can Predict the Pregnancy Outcomes in Human and Intraperitoneal Administration of MUC16 can Rescue Pregnancy Losses in Mouse Models

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Abstract

Mucin 16 (MUC16) participates in the process of embryo implantation, but few studies have examined the association between MUC16 and pregnancy loss. To investigate this association, the expression of MUC16 in serum and decidua was compared between women with pregnancy loss and ongoing pregnancies. In vitro experiments and animal models were used to explore the role and underlying mechanisms of MUC16 in pregnancy loss. In human study, the expression of MUC16 in serum and decidua was both consistently lower in the women with pregnancy loss compared with those in women with ongoing pregnancies. In vitro experiments revealed the interaction of MUC16 with peripheral blood natural killer (pNK) cells. MUC16 changed the phenotype and reduced the pro-inflammation ability of pNK cells. MUC16 also inhibited the cytotoxicity of pNK cells through the Src homology region 2 domain-containing phosphatase-1/extracellular signal-regulated kinase (SHP-ERK) pathway. Furthermore, MUC16 promoted the migration, invasion and tube formation of trophoblast cells by co-culturing together with pNK cells. In vivo experiments, the mouse model of abortion was used to further confirm that intraperitoneal administration of MUC16 could rescue the pregnancy loss. This study reveals the still-unknown connection between MUC16 and pNK cells and indicates that MUC16 provides a novel method for future prediction and treatment of unfavorable pregnancy outcomes.

Graphical Abstract

Representative cartoon illustrating the effects of MUC16. A. The direct effects of MUC16 were to shape the phenotype and decrease TNF-α secretion of pNK cells, while inhibiting their cytotoxicity through the SHP-ERK pathway. B. The indirect effects of MUC16 were to promote the tube formation and invasion, migration of extravillous trophoblast cells (EVTs) by co-culturing with pNK cells.

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Acknowledgements

We thank former members of the Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine for technical assistance.This research was supported by the Huadong Medicine Joint Funds of the Zhejiang Provincial Natural Science Foundation of China (Grant No. LHDMZ22H040001). We thank Liwen Bianji (Edanz) (www.liwenbianji.cn/) for editing the English text of a draft of this manuscript.

Funding

This research was supported by the Huadong Medicine Joint Funds of the Zhejiang Provincial Natural Science Foundation of China (Grant No. LHDMZ22H040001).

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Authors and Affiliations

  1. Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China

    Xiaona Huang, Huizhen Lin, Yue Zhao, Peixin Wang, Hanqi Ying, Songying Zhang & Liu Liu

  2. Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, Hangzhou, China

    Xiaona Huang, Huizhen Lin, Yue Zhao, Peixin Wang, Hanqi Ying, Songying Zhang & Liu Liu

  3. Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Hangzhou, China

    Xiaona Huang, Huizhen Lin, Yue Zhao, Peixin Wang, Hanqi Ying, Songying Zhang & Liu Liu

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  1. Xiaona Huang
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Contributions

Conceptualization, Xiaona Huang, Liu Liu; methodology, Xiaona Huang, Huizhen Lin, Yue Zhao; Data analysis, Xiaona Huang, Huizhen Lin, Peixin Wang, Hanqi Ying; Supervision: LiuLiu; Writing – Original Draft: Xiaona Huang, Huizhen Lin; Writing – Review & Editing: Songying Zhang, Liu Liu.

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Correspondence to Liu Liu.

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The authors declare they have no financial interests.

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The authors declare no competing interests.

Ethical Approval

All experimental work included in this work was performed in compliance with ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments, and the study protocol was approved by approved by the institutional review board of Sir Run Run Shaw hospital (No.2023–0309). The animal experiment protocols were approved by the Zhejiang University Institutional Animal Care and Use Committee (No.26165).

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Informed consent was obtained from all individual participants included in the study.

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The authors declare no competing interests.

Ethics Approval

This retrospective chart review study involving human participants was in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The Human Investigation Committee (IRB) of Zhejiang University approved this study.

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Informed consent was obtained from all individual participants included in the study.

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The authors affirm that human research participants provided informed consent for publication of the images in Fig. 1E and 1F.

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Huang, X., Lin, H., Zhao, Y. et al. MUC16 can Predict the Pregnancy Outcomes in Human and Intraperitoneal Administration of MUC16 can Rescue Pregnancy Losses in Mouse Models. Reprod. Sci. (2024). https://doi.org/10.1007/s43032-024-01550-7

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