title: FSH receptor (FSHR) expression in human extragonadal reproductive tissues and the developing placenta, and the impact of its deletion on pregnancy in mice.
abstract: Expression and function of the follicle-stimulating hormone receptor (FSHR) in females were long thought to be limited to the ovary. Here, however, we identify extragonadal FSHR in both the human female reproductive tract and the placenta, and test its physiological relevance in mice. We show that in nonpregnant women FSHR is present on: endothelial cells of blood vessels in the endometrium, myometrium, and cervix; endometrial glands of the proliferative and secretory endometrium; cervical glands and the cervical stroma; and (at low levels) stromal cells and muscle fibers of the myometrium. In pregnant women, placental FSHR was detected as early as 8-10 wk of gestation and continued through term. It was expressed on: endothelial cells in fetal portions of the placenta and the umbilical cord; epithelial cells of the amnion; decidualized cells surrounding the maternal arteries in the maternal decidua; and the stromal cells and muscle fibers of the myometrium, with particularly strong expression at term. These findings suggest that FSHR expression is upregulated during decidualization and upregulated in myometrium as a function of pregnancy. The presence of FSHR in the placental vasculature suggests a role in placental angiogenesis. Analysis of genetically modified mice in which Fshr is lacking in fetal portions of the placenta revealed adverse effects on fetoplacental development. Our data further demonstrate FSHB and CGA mRNAs in placenta and uterus, consistent with potential local sources of FSH. Collectively, our data suggest heretofore unappreciated roles of extragonadal FSHR in female reproductive physiology.
authors.affiliation: Department of Molecular Biophysics and Physiology, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa.
authors.forename: Julie A W
authors.initials: JA
authors.lastname: Stilley
authors.affiliation: Department of Molecular Biophysics and Physiology, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa.
authors.forename: Debora E
authors.initials: DE
authors.lastname: Christensen
authors.affiliation: Department of Molecular Biophysics and Physiology, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa.
authors.forename: Kristin B
authors.initials: KB
authors.lastname: Dahlem
authors.affiliation: Department of Molecular Biophysics and Physiology, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa.
authors.forename: Rongbin
authors.initials: R
authors.lastname: Guan
authors.affiliation: Department of Obstetrics and Gynecology, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa.
authors.forename: Donna A
authors.initials: DA
authors.lastname: Santillan
authors.affiliation: Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: England
authors.affiliation: Department of Obstetrics and Gynecology, Meharry Medical Center, Nashville, Tennessee.
authors.forename: Ayman
authors.initials: A
authors.lastname: Al-Hendy
authors.affiliation: Department of Pathology, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Kirby
authors.affiliation: Department of Molecular Biophysics and Physiology, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa deborah-segaloff@uiowa.edu.
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Segaloff
mesh_terms: D000328:Adult; D000818:Animals; D002584:Cervix Uteri / Q000098:blood supply / Q000166:cytology / Q000378:metabolism; D004717:Endometrium / Q000098:blood supply / Q000166:cytology / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005321:Extraembryonic Membranes / Q000098:blood supply / Q000166:cytology / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007150:Immunohistochemistry; D018345:Mice, Knockout; D009215:Myometrium / Q000098:blood supply / Q000166:cytology / Q000378:metabolism; D010920:Placenta / Q000098:blood supply / Q000166:cytology / Q000378:metabolism*; D010929:Placentation; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D011962:Receptors, FSH / Q000235:genetics / Q000378:metabolism*; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D014470:Umbilical Cord / Q000166:cytology / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D012333:RNA, Messenger; D011962:Receptors, FSH
keywords: FSH receptor; cervix; follicle-stimulating hormone; gonadotropin; placenta; pregnancy; uterus
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