title: Novel three dimensional human endocervix cultures respond to 28-day hormone treatment.
abstract: The endocervix has both anatomical and biological functions that participate in the delicate balance between tolerance necessary for conception and protection from pathogens. Our goal was to develop a robust 3-dimensional (3D) endocervix model that was a reliable representation of the in vivo tissues and to identify the physiological responses to changing levels of steroid hormones during a 28-day time period. Human endocervical cells were grown on polystyrene scaffolds, and the morphologic and hormonal responses of cultured cells were assessed in response to fluctuating levels of estradiol (E2) or progesterone (P4). Morphologically, the 3D cultures were composed of a mixed population of cells, including epithelial and stromal cells. Treatment with E2 and P4 (d 28) increased cell growth and proliferation as compared with no treatment control. Cells expressed estrogen receptor and P4 receptor and produced both neutral and acidic mucins, including Mucin 16. In addition, a 45-plex Luminex assay identified numerous factors secreted and regulated by hormones. Specifically, IL-1β and leukemia inhibitory factor significantly decreased in the presence of E2 and P4 as compared with the no hormone control at day 26. Cotreatment with RU486 (mifepristone) attenuated the inhibition of IL-1β and leukemia inhibitory factor secretion. In summary, a robust, novel 3D endocervical culture was developed, and physiologic responses to the menstrual cycle mimic of E2 and P4 levels for a period of 28 days were identified.
authors: Division of Reproductive Science in Medicine (S.Y.A., Y.Y., M.E.P., T.K.W., J.J.K.), Department of Obstetrics and Gynecology, and Department of Cell and Molecular Biology (T.J.H.), Northwestern University, Chicago, Illinois 60611; Department of Medicinal Chemistry and Pharmacognosy (J.E.B.), University of Illinois at Chicago, Chicago, Illinois 60607; and Division of Reproductive Endocrinology and Infertility (M.E.P.), Department of Obstetrics and Gynecology, Northwestern University, Chicago, Illinois 60611.
authors: Sevim Yildiz
authors: SY
authors: Arslan
authors: Yanni
authors: Y
authors: Yu
authors: Joanne E
authors: JE
authors: Burdette
authors: Mary Ellen
authors: ME
authors: Pavone
authors: Thomas J
authors: TJ
authors: Hope
authors: Teresa K
authors: TK
authors: Woodruff
authors: J Julie
authors: JJ
authors: Kim
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D053605:Leukemia Inhibitory Factor / Q000235:genetics / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D053605:Leukemia Inhibitory Factor; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D011374:Progesterone; D004958:Estradiol
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