Endometrial pyruvate kinase M2 is essential for decidualization during early pregnancy

in Journal of Endocrinology
Authors:
Yan Su Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Chongqing, China
Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, China

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Sujuan Guo Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Chongqing, China
Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, China

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Chunyan Liu Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Chongqing, China
Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, China

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Na Li Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Chongqing, China
Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, China

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Shuang Zhang Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Chongqing, China
Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, China

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Yubin Ding Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Chongqing, China
Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, China

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Xuemei Chen Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Chongqing, China
Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, China

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Junlin He Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Chongqing, China
Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, China

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Xueqing Liu Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Chongqing, China
Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, China

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Yingxiong Wang Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Chongqing, China
Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, China

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Rufei Gao Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Chongqing, China
Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, China

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Correspondence should be addressed to Y-X Wang or R-F Gao: yxwang@cqmu.edu.cn or gao_ru_fei@cqmu.edu.cn

*(Y Su and S Guo contributed equally to this work)

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Embryo implantation is essential for normal pregnancy. Decidualization is known to facilitate embryo implantation and maintain pregnancy. Uterine stromal cells undergo transformation into decidual cells after embryo attachment to the endometrium. Pyruvate kinase M2 (PKM2) is a rate limiting enzyme in the glycolysis process which catalyzes phosphoenolpyruvic acid into pyruvate. However, little is known regarding the role of PKM2 during endometrial decidualization. In this study, PKM2 was found to be mainly located in the uterine glandular epithelium and luminal epithelium on day 1 and day 4 of pregnancy and strongly expressed in the decidual zone after embryo implantation. PKM2 was dramatically increased with the onset of decidualization. Upon further exploration, PKM2 was found to be more highly expressed at the implantation sites than at the inter-implantation sites on days 5 to 7 of pregnancy. PKM2 expression was also significantly increased after artificial decidualization both in vivo and in vitro. After PKM2 expression was knocked down by siRNA, the number of embryo implantation sites in mice on day 7 of pregnancy was significantly reduced, and the decidualization markers BMP2 and Hoxa10 were also obviously downregulated in vivo and in vitro. Downregulated PKM2 could also compromise cell proliferation in primary endometrial stromal cells and in Ishikawa cells. The migration rate of Ishikawa cells was also obviously suppressed by si-PKM2 according to the wound healing assay. In conclusion, PKM2 might play an important role in decidualization during early pregnancy, and cell proliferation might be one pathway for PKM2 regulated decidualization.

 

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