Identification of proteins highly expressed in uterine fluid from mice with hydrometra

• Published in: Biochemical and biophysical research communications Vol. 466; no. 4; pp. 650 - 655
• Main Authors: Antonson, Per, Nalvarte, Ivan, Varshney, Mukesh, Xu, Li, Windahl, Sara H., Humire, Patricia, Ohlsson, Claes, Gustafsson, Jan-Åke, Dahlman-Wright, Karin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30.10.2015
• Subjects: ANALYSIS; Animals; BETA-CELLS; Biochemistry & Molecular Biology; Biochemistry and Molecular Biology; Biokemi och molekylärbiologi; Biophysics; Chitinase-3-Like Protein 1; Complement C3 - genetics; Complement C3 - metabolism; Endocrinology and Diabetes; Endokrinologi och diabetes; ER-ALPHA; Estradiol - blood; Estrogen; Estrogen receptor; Estrogen Receptor alpha - deficiency; Estrogen Receptor alpha - genetics; Estrogen Receptor alpha - metabolism; ESTROGEN-RECEPTOR-ALPHA; Estrous Cycle - blood; Estrous Cycle - genetics; Estrous Cycle - metabolism; Female; Gene Expression; GENERATION; Glycoproteins - blood; Glycoproteins - genetics; Glycoproteins - metabolism; HUMAN AMNIOTIC-FLUID; Knockout; LACTOFERRIN; Lactoferrin - genetics; Lactoferrin - metabolism; MECHANISM; Medicin och hälsovetenskap; Mice; Mice, Inbred C57BL; Mice, Knockout; Proteomics; Rats; RNA, Messenger - genetics; RNA, Messenger - metabolism; SECRETOME; Serpins - genetics; Serpins - metabolism; SUBSTRATE-2; Uterine Diseases - genetics; Uterine Diseases - metabolism; Uterus; Uterus - metabolism; C3; Estrogen receptor; MALDI-TOF-MS; Uterus; KO; Estrogen; Proteomics; CHI3L1; LF; E2; ER; Knockout
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2015.09.099

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/ERαKO 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/ERαKO 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. •Cre/ERαKO mice have increased serum estradiol levels and develop hydrometra.•Cre/ERαKO mice have reduced ERα levels in the hypothalamus.•We identified LF, C3 and CHI3L1 as highly expressed proteins in hydrometra fluid.•Chronically elevated serum estradiol levels increase LF, C3 and CHI3L1 in uterus.