PMID- 29684808 OWN - NLM STAT- MEDLINE DCOM- 20181121 LR - 20190501 IS - 1432-0436 (Electronic) IS - 0301-4681 (Print) IS - 0301-4681 (Linking) VI - 101 DP - 2018 May-Jun TI - Tissue interactions and estrogenic response during human female fetal reproductive tract development. PG - 39-45 LID - S0301-4681(18)30034-3 [pii] LID - 10.1016/j.diff.2018.04.002 [doi] AB - The role of tissue interactions was explored to determine whether epithelial differentiation within the developing human reproductive tract is induced and specified by mesenchyme in tissue recombinants composed of mouse vaginal mesenchyme + human uterine tubal epithelium (mVgM+hTubE). The tissue recombinants were grown in DES-treated ovariectomized athymic mice. After 2-4 weeks of in vivo growth, several vaginal specific features were expressed in the human tubal epithelium. The mesenchyme-induced effects included morphological change as well as expression of several immunohistochemical markers. Although the mesenchyme-induced shift in vaginal differentiation in the human tubal epithelium was not complete, the partial induction of vaginal markers in human tubal epithelium verifies the importance of mesenchymal-epithelial interactions in development of the human female reproductive tract. In a separate experiment, DES-induction of uterine epithelial progesterone receptor (PGR) and estrogen receptor 1 (ESR1) was explored in tissue recombinants composed of wild-type or Esr1KO mouse uterine mesenchyme + human fetal uterine epithelium (wt UtM+hUtE and Esr1KO UtM+hUtE). The rationale of this experiment was to determine whether DES-induction of PGR and ESR1 is mediated directly via epithelial ESR1 or indirectly (paracrine mechanism) via mesenchymal ESR1. DES-induction of uterine epithelial ESR1 and PGR in Esr1KO UtM+hUtE tissue recombinants (devoid of mesenchymal ESR1) formally eliminates the paracrine mechanism and demonstrates that DES induction of human uterine epithelial ESR1 and PGR is directly mediated via epithelial ESR1. CI - Copyright (c) 2018 International Society of Differentiation. Published by Elsevier B.V. All rights reserved. FAU - Cunha, Gerald R AU - Cunha GR AD - Department of Urology, University of California, 400 Parnassus Avenue, San Francisco, CA 94143, United States. Electronic address: Gerald.Cunha@ucsf.edu. FAU - Kurita, Takeshi AU - Kurita T AD - Department of Cancer Biology and Genetics, College of Medicine, Comprehensive Cancer Center, Ohio State University, 812 Biomedical Research Tower, 460 W. 12th Avenue, Columbus, OH 43210, United States. FAU - Cao, Mei AU - Cao M AD - Department of Urology, University of California, 400 Parnassus Avenue, San Francisco, CA 94143, United States. FAU - Shen, Joel AU - Shen J AD - Department of Urology, University of California, 400 Parnassus Avenue, San Francisco, CA 94143, United States. FAU - Cooke, Paul S AU - Cooke PS AD - Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, 1333 Center Drive, Gainesville, FL 32610, United States. FAU - Robboy, Stanley J AU - Robboy SJ AD - Department of Pathology, Duke University Medical Center, DUMC 3712, Durham, NC 27710, United States. FAU - Baskin, Laurence S AU - Baskin LS AD - Department of Urology, University of California, 400 Parnassus Avenue, San Francisco, CA 94143, United States. LA - eng GR - R01 CA154358/CA/NCI NIH HHS/United States GR - R01 DK058105/DK/NIDDK NIH HHS/United States GR - R21 HD088006/HD/NICHD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20180418 PL - England TA - Differentiation JT - Differentiation; research in biological diversity JID - 0401650 RN - 0 (Estrogen Receptor alpha) RN - 0 (Receptors, Progesterone) SB - IM MH - Animals MH - Cell Differentiation/*physiology MH - Epithelial Cells/cytology MH - Epithelium/*growth & development MH - Estrogen Receptor alpha/metabolism MH - Female MH - Genitalia, Female MH - Humans MH - Mesoderm/cytology MH - Mice MH - Receptors, Progesterone/*metabolism MH - Uterus/*growth & development/metabolism PMC - PMC5993605 MID - NIHMS961365 OTO - NOTNLM OT - Diethylstilbestrol OT - Estrogen receptor OT - Estrogenic response OT - Human female fetal reproductive tract OT - Mesenchymal-epithelial interactions OT - Progesterone receptor EDAT- 2018/04/24 06:00 MHDA- 2018/11/22 06:00 PMCR- 2019/05/01 CRDT- 2018/04/24 06:00 PHST- 2018/03/15 00:00 [received] PHST- 2018/04/11 00:00 [revised] PHST- 2018/04/16 00:00 [accepted] PHST- 2018/04/24 06:00 [pubmed] PHST- 2018/11/22 06:00 [medline] PHST- 2018/04/24 06:00 [entrez] PHST- 2019/05/01 00:00 [pmc-release] AID - S0301-4681(18)30034-3 [pii] AID - 10.1016/j.diff.2018.04.002 [doi] PST - ppublish SO - Differentiation. 2018 May-Jun;101:39-45. doi: 10.1016/j.diff.2018.04.002. Epub 2018 Apr 18.