title: Identification of proteins highly expressed in uterine fluid from mice with hydrometra.
abstract: Estrogen receptor alpha (ERα) is an important regulator of the estrous cycle and mice with global ERα deletion, as well as some conditional knockout mouse lines, have an interruption in the estrous cycle. In this study we observed that conditional ERα knockout mice where the Cre gene is regulated by the rat insulin promoter (RIP), RIP-Cre/ERα(KO) mice, have a 3.7-fold increase in serum 17β-estradiol levels, blocked estrous cycle, and develop a fluid-filled uterus (hydrometra). Using a proteomics approach, we identified three proteins, lactoferrin, complement C3 and chitinase 3-like protein 1 (CHI3L1), as highly expressed proteins in hydrometra fluid. The mRNA levels of the corresponding genes were more than 50-fold higher in RIP-Cre/ERα(KO) uterus compared to controls. High expression of CHI3L1 in the uterine fluid was not reflected as elevated levels in the serum. The high expression of lactoferrin, complement C3 and CHI3L1 in the uterine fluid, in association with elevated estrogen levels, prompted us to address if the expression of these genes is related to reproduction. However, gonadotropin treatment of mice reduced the uterine expression of these genes in a model of in vitro fertilization. Our findings identify lactoferrin, complement C3 and CHI3L1 as highly expressed proteins in hydrometra fluid in association with chronically elevated serum estradiol levels.
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Novum, SE-141 83, Huddinge, Sweden. Electronic address: per.antonson@ki.se.
authors.forename: Per
authors.initials: P
authors.lastname: Antonson
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Novum, SE-141 83, Huddinge, Sweden.
authors.forename: Ivan
authors.initials: I
authors.lastname: Nalvarte
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Novum, SE-141 83, Huddinge, Sweden.
authors.forename: Mukesh
authors.initials: M
authors.lastname: Varshney
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Novum, SE-141 83, Huddinge, Sweden.
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.affiliation: Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Sara H
authors.initials: SH
authors.lastname: Windahl
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Novum, SE-141 83, Huddinge, Sweden.
authors.forename: Patricia
authors.initials: P
authors.lastname: Humire
authors.affiliation: Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Claes
authors.initials: C
authors.lastname: Ohlsson
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Novum, SE-141 83, Huddinge, Sweden; Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX, 77204, USA.
authors.forename: Jan-Åke
authors.initials: JÅ
authors.lastname: Gustafsson
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Novum, SE-141 83, Huddinge, Sweden; SciLifeLab, Department of Biosciences and Nutrition, Karolinska Institutet, S-171 21, Solna, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Dahlman-Wright
mesh_terms: D000818:Animals; D000071451:Chitinase-3-Like Protein 1; D003176:Complement C3 / Q000235:genetics / Q000378:metabolism; D004958:Estradiol / Q000097:blood; D047628:Estrogen Receptor alpha / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D030762:Estrous Cycle / Q000097:blood / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006023:Glycoproteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D007781:Lactoferrin / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D014591:Uterine Diseases / Q000235:genetics / Q000378:metabolism; D014599:Uterus / Q000378:metabolism*
chemical_list: C509289:Chil1 protein, mouse; D000071451:Chitinase-3-Like Protein 1; D003176:Complement C3; D047628:Estrogen Receptor alpha; D006023:Glycoproteins; C552902:Ltf protein, mouse; D012333:RNA, Messenger; D015843:Serpins; C029708:uterine luminal fluid proteins; D004958:Estradiol; D007781:Lactoferrin
keywords: Estrogen; Estrogen receptor; Knockout; Proteomics; Uterus