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However, its clinical use is hampered by the development of pathologic progesterone receptor modulator-associated endometrial changes (PAECs). The current study was designed to test the hypothesis that UPA-induced PAECs are associated with deranged expression of some metabolic genes. In addition, metformin can mitigate UPA-induced PAECs through modulating the expression of these genes. In the present study, twenty-eight female non-pregnant, nulligravid Wistar rats were treated with UPA (0.1\u00a0mg\/kg\/day, intragastric) and\/or metformin (50\u00a0mg\/kg\/day, intragastric) for 8\u00a0weeks. Our results demonstrated that co-treatment with metformin significantly reduced UPA-induced PAECs. In addition, co-treatment with metformin and UPA was associated with significant increase in the Bax and significant reduction in Bcl-2, PCNA, Cyclin-D1and ER-\u03b1 as compared to treatment with UPA alone. Furthermore, treatment with UPA alone was associated with deranged expression of 3-phosphoglycerate dehydrogenase (3-PHGDH), glucose-6-phosphate dehydrogenase (G6PD), transketolase (TKT), fatty acid synthase (FAS) and CD36. Most importantly, co-treatment with metformin markedly reduced UPA-induced altered expression of these metabolic genes in endometrial tissues. In conclusion, UPA-induced PAECs are associated with altered expression of genes involved in cell proliferation, apoptosis, estrogen receptor, glucose metabolism and lipid metabolism. Co-treatment with metformin abrogated UPA-induced PAECs most likely through the modulation of the expression of these genes.<\/jats:p>","DOI":"10.1038\/s41598-021-88346-w","type":"journal-article","created":{"date-parts":[[2021,4,23]],"date-time":"2021-04-23T10:12:30Z","timestamp":1619172750000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Glucose and fatty acid metabolism involved in the protective effect of metformin against ulipristal-induced endometrial changes in rats"],"prefix":"10.1038","volume":"11","author":[{"given":"Marwa S.","family":"Hamza","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman","family":"Ramadan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salama A.","family":"Salama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,4,23]]},"reference":[{"key":"88346_CR1","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1016\/S0039-128X(03)00130-2","volume":"68","author":"EE Gainer","year":"2003","unstructured":"Gainer, E. 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