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Decreased Glycolysis at Menstruation is Associated with Increased Menstrual Blood Loss

  • Abnormal uterine bleeding: Original Article
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Abstract

Heavy menstrual bleeding (HMB) is common and severely affects the quality of life of the afflicted women. While HMB is known to be caused by impaired endometrial repair after menstruation, its more proximate cause remains unknown. To investigate whether glycolysis plays any role in endometrial repair and thus HMB, we conducted two mouse experiments using a mouse model of simulated menstruation. We performed immunohistochemistry analyses of proteins involved in glycolysis as well as pro- and anti-inflammatory cytokines in endometrium from decidualized and non-decidualized uterine horns. We also assessed the extent of endometrial repair by staging endometrial morphology from decidualization to full repair using histological scoring of uterine sections and quantitated the amount of menstrual blood loss (MBL). In addition, we employed the scratch assay and the CCK-8 assay to evaluate the effect of glycolysis suppression on cellular migration and proliferation, respectively. Finally, we performed an immunohistochemistry analysis of HK2 in endometrium from women with adenomyosis who experienced either moderate/heavy or excessive MBL. We found that endometrial repair coincided with increased glycolysis in endometrium and glycolysis suppression delayed endometrial repair, resulting in increased MBL. Additionally, glycolysis suppression significantly inhibited the proliferative and migratory capability of endometrial cells, and disrupted normal endometrial repair even when hypoxia was maintained. Women with adenomyosis who experienced excessive MBL had significantly lower HK2 staining than those who experienced moderate/heavy MBL. Thus, our study highlights the importance of glycolysis as well as inflammation in optimal endometrial repair, and provides clues for the cause of HMB in women with adenomyosis.

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Data Availability

The data presented in this study are available upon written request from the corresponding author explaining the use and purposes.

Code Availability

Not applicable.

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Acknowledgment

We acknowledge the generous contribution from Professor Hilary Critchley of the University of Edinburgh for advice on the protocol for development of the simulated mouse model of menstruation and for her constructive commentary during manuscript preparation. We also thank Dr. Xiaojun Chen for providing the ECC-1 cell line.

Funding

This research was supported by grants 82071623 (SWG) and 81871144 (XSL) from the National Natural Science Foundation of China, an Excellence in Centers of Clinical Medicine grant (2017ZZ01016) from the Science and Technology Commission of Shanghai Municipality, and grant SHDC2020CR2062B from Shanghai Shenkang Center for Hospital Development.

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Authors and Affiliations

  1. Department of Gynecology, Shanghai OB/GYN Hospital, Fudan University, Shanghai, 200011, China

    Chenyu Mao & Xishi Liu

  2. Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Fudan University, Shanghai, China

    Xishi Liu & Sun-Wei Guo

  3. Research Institute, Shanghai OB/GYN Hospital, Fudan University, Shanghai, 200011, China

    Sun-Wei Guo

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Contributions

S.-W.G. conceived and designed the entire study, carried out data analysis and interpretation, and drafted the manuscript. C.M. carried out the entire experiments and participated in writing. X.L. participated in the study design, patient recruitment and writing. All participated in the writing and approved the final version of the manuscript.

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Correspondence to Sun-Wei Guo.

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Conflicts of Interest

SWG provided consultancy advice for MSD R&D, Chugai Pharmaceutical Co., and BioHaven Pharmaceuticals, but these activities had no bearing on this work. All authors state that they have no conflicts of interest to declare.

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This study was approved by the institutional ethics review board of Shanghai OB/GYN Hospital, Fudan University (No. 2020-75).

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All subjects enrolled in this study signed an informed consent for all the procedures and to allow data collection and analysis for research purposes.

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Human Rights Statements and Informed Consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and its later amendments. Informed consent was obtained from all patients for being included in the study. The study was approved by the institutional ethics review board of Shanghai OB/GYN Hospital, Fudan University (No. 2020-75). Each patient enrolled in this study signed an informed consent for all the procedures and to allow data collection and analysis for research purposes.

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Mao, C., Liu, X. & Guo, SW. Decreased Glycolysis at Menstruation is Associated with Increased Menstrual Blood Loss. Reprod. Sci. 30, 928–951 (2023). https://doi.org/10.1007/s43032-022-01066-y

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