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Response of xenografts of developing human female reproductive tracts to the synthetic estrogen, diethylstilbestrol.

Publication ,  Journal Article
Cunha, GR; Kurita, T; Cao, M; Shen, J; Robboy, SJ; Baskin, L
Published in: Differentiation
2017

Human female fetal reproductive tracts 9.5-22 weeks of gestation were grown for 1 month in ovariectomized athymic adult female mouse hosts that were either untreated or treated continuously with diethylstilbestrol (DES) via subcutaneous pellet. Normal morphogenesis and normal patterns of differentiation marker expression (KRT6, KRT7, KRT8, KRT10, KRT14, KRT19, ESR1, PGR, TP63, RUNX1, ISL1, HOXA11 and α-ACT2) were observed in xenografts grown in untreated hosts and mimicked observations of previously reported (Cunha et al., 2017) non-grafted specimens of comparable age. DES elicited several notable morphological affects: (a) induction of endometrial/cervical glands, (b) increased plication (folding) of tubal epithelium, (c) stratified squamous maturation of vaginal epithelium and (d) vaginal adenosis. DES also induced ESR1 in epithelia of the uterine corpus, cervix and globally induced PGR in most cells of the developing human female reproductive tract. Keratin expression (KRT6, KRT7, KRT8, KRT14 and KRT19) was minimally affected by DES. Simple columnar adenotic epithelium was devoid of TP63 and RUNX1, while DES-induced mature vaginal epithelium was positive for both transcription factors. Another striking effect of DES was observed in grafts of human uterine tube, in which DES perturbed smooth muscle patterning. These results define for the first time IHC protein markers of DES action on the developing human reproductive tract, which provide bio-endpoints of estrogen-induced teratogenesis in the developing human female reproductive tract for future testing of estrogenic endocrine disruptors.

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Published In

Differentiation

DOI

EISSN

1432-0436

Publication Date

2017

Volume

98

Start / End Page

35 / 54

Location

England

Related Subject Headings

  • Uterus
  • Transcription Factors
  • Humans
  • Heterografts
  • Genitalia, Female
  • Female
  • Estradiol Congeners
  • Epithelium
  • Epithelial Cells
  • Diethylstilbestrol
 

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Cunha, G. R., Kurita, T., Cao, M., Shen, J., Robboy, S. J., & Baskin, L. (2017). Response of xenografts of developing human female reproductive tracts to the synthetic estrogen, diethylstilbestrol. Differentiation, 98, 35–54. https://doi.org/10.1016/j.diff.2017.10.001
Cunha, Gerald R., Takeshi Kurita, Mei Cao, Joel Shen, Stanley J. Robboy, and Laurence Baskin. “Response of xenografts of developing human female reproductive tracts to the synthetic estrogen, diethylstilbestrol.Differentiation 98 (2017): 35–54. https://doi.org/10.1016/j.diff.2017.10.001.
Cunha GR, Kurita T, Cao M, Shen J, Robboy SJ, Baskin L. Response of xenografts of developing human female reproductive tracts to the synthetic estrogen, diethylstilbestrol. Differentiation. 2017;98:35–54.
Cunha, Gerald R., et al. “Response of xenografts of developing human female reproductive tracts to the synthetic estrogen, diethylstilbestrol.Differentiation, vol. 98, 2017, pp. 35–54. Pubmed, doi:10.1016/j.diff.2017.10.001.
Cunha GR, Kurita T, Cao M, Shen J, Robboy SJ, Baskin L. Response of xenografts of developing human female reproductive tracts to the synthetic estrogen, diethylstilbestrol. Differentiation. 2017;98:35–54.
Journal cover image

Published In

Differentiation

DOI

EISSN

1432-0436

Publication Date

2017

Volume

98

Start / End Page

35 / 54

Location

England

Related Subject Headings

  • Uterus
  • Transcription Factors
  • Humans
  • Heterografts
  • Genitalia, Female
  • Female
  • Estradiol Congeners
  • Epithelium
  • Epithelial Cells
  • Diethylstilbestrol