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Decidualization deficiency is considered a contributing factor to the development of PE. CTP synthetase (CTPS) which is the rate\u2010limiting enzyme in the CTP de novo biosynthesis, is essential for nucleic acid synthesis and cellular energy metabolism, and often appears as cytoophidium in many cell types. Here, we found that the expression of CTPS was significantly downregulated in decidual tissues of patients with severe PE compared with healthy pregnant women. During in vitro decidualization, changes in CTPS were accompanied by opposite fluctuation of the AMPK signaling pathway. Moreover, the downregulation of CTPS by glutamine analogs or <jats:italic>CTPS<\/jats:italic> small interfering RNA inhibited the decidualization process and the AMPK signaling pathway. Investigating the underlying mechanism of action by co\u2010immunoprecipitation coupled with mass spectrometry showed that CTPS interacted with ATP synthase (ATPS) and maintained the content of ATP on Day 3 of decidualization. However, when combined with mitochondrial stress protein STRESS\u201070 instead of ATPS, the concentration of ATP on Day 6 of induction was reduced. Corresponding to this, CTPS was mainly distributes in the cytoplasm on Day 3 of induction, while it appeared both in the cytoplasm and the nucleus on Day 6 in decidualized cells, which was similar to that in cells before induction. In summary, we believe that CTPS plays an important role in decidualization by participating in energy metabolism. Abnormal expression of CTPS in decidualization would lead to abnormal decidualization and consequently result in the occurrence of PE.<\/jats:p>","DOI":"10.1002\/jcp.30326","type":"journal-article","created":{"date-parts":[[2021,2,14]],"date-time":"2021-02-14T14:08:54Z","timestamp":1613311734000},"page":"6520-6533","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Energy deficiency caused by CTPS downregulation in decidua may contribute to pre\u2010eclampsia by impairing decidualization"],"prefix":"10.1002","volume":"236","author":[{"given":"Ke","family":"Ma","sequence":"first","affiliation":[{"name":"Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences Shandong Normal University  Ji'nan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Li","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory of Animal 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