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In the present study, pregnant mice were administered either flutamide (300 mg kg\u22121 day\u22121, p.o.) on an equivalent volume of soybean oil (control) on Days 12\u201318 of gestation. Eight weeks after birth, female offspring in the flutamide-treated group had a lower bodyweight and lower ovarian and uterine weights, but there was no significant difference in uterine and ovarian weights normalised by bodyweight between the flutamide-treated and control groups. Furthermore, histopathological changes were observed in all uteri and ovaries in the flutamide-treated group, with fewer and less-developed follicles in the ovaries. In both the uteri and ovaries, flutamide increased the expression of UPR members, although the expression of cell cycle-related genes remained unchanged compared with the control group. Flutamide increased the expression of all autophagy- and apoptosis-related genes evaluated in the uterus, as well as some in the ovary. The results suggest that the in utero exposure of mice to flutamide may contribute to uterine and ovarian damage in the offspring, with endoplasmic reticulum stress possibly triggered by the UPR leading to the induction of excessive autophagy and apoptosis.<\/jats:p>","DOI":"10.1071\/rd20287","type":"journal-article","created":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T17:50:33Z","timestamp":1617213033000},"page":"466-475","source":"Crossref","is-referenced-by-count":5,"title":["Flutamide induces uterus and ovary damage in the mouse via apoptosis and excessive autophagy of cells following triggering of the unfolded protein response"],"prefix":"10.1071","volume":"33","author":[{"given":"Haiming","family":"Yu","sequence":"first","affiliation":[{"name":"ADepartment of Critical Medicine, The First Affiliated Hospital of Hunan Normal University (The People\u2019s Hospital of Hunan Province), Changsha 410002, PR China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqing","family":"Zhou","sequence":"additional","affiliation":[{"name":"BKey Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Medical School, Hunan Normal University, Changsha 410013, PR China."},{"name":"CDepartment of Infection Control, The Eighth Hospital of Xi\u2019An\/Shanxi Provincial Infectious Disease Hospital, Xi\u2019An 710061, PR China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujing","family":"Zhang","sequence":"additional","affiliation":[{"name":"BKey Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Medical School, Hunan Normal University, Changsha 410013, PR China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kexin","family":"Wen","sequence":"additional","affiliation":[{"name":"BKey Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Medical School, Hunan Normal University, Changsha 410013, PR China."},{"name":"DChangsha Center for Disease Control and Prevention of Hunan Province, Changsha 410004, PR China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengli","family":"Yan","sequence":"additional","affiliation":[{"name":"BKey Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Medical School, Hunan Normal University, Changsha 410013, PR China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hu","family":"Fu","sequence":"additional","affiliation":[{"name":"BKey Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Medical School, Hunan Normal University, Changsha 410013, PR China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8722-6445","authenticated-orcid":true,"given":"Yongfei","family":"Zhu","sequence":"additional","affiliation":[{"name":"BKey Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Medical School, Hunan Normal University, Changsha 410013, PR China."},{"name":"ECorresponding author. 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