Primary endometrial 3D co-cultures: A comparison between human and rat endometrium

A. D. van den Brand, E. Rubinstein, P. C. de Jong, M. van den Berg, M. B.M. van Duursen

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Human and rat reproductive systems differ significantly with respect to hormonal cyclicity and endometrial cell behavior. However, species-differences in endometrial cell responses upon hormonal stimulation and exposure to potentially toxic compounds are poorly characterized. In this study, human and rat endometrial hormonal responses were assessed in vitro using a 3D co-culture model of primary human and rat endometrial cells. The models were exposed to the aryl hydrocarbon receptor (AHR) ligands 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), laquinimod, and its AHR active metabolite DELAQ. In both the human and rat endometrial models, estrogen receptor and progesterone receptor gene expression was modulated by the hormonal treatments, comparable to the in vivo situation. AHR gene expression in the human endometrial model did not change when exposed to hormones. In contrast, AHR expression decreased 2-fold in the rat model when exposed to predominantly progesterone, which resulted in a 2.8-fold attenuation of gene expression induction of cytochrome P450 1A1 (CYP1A1) by TCDD. TCDD and DELAQ, but not laquinimod, concentration-dependently induced CYP1A1 gene expression in both human and rat endometrial models. Interestingly, the relative degree of DELAQ to induce CYP1A1 was higher than that of TCDD in the human model, while it was lower in the rat model. These data clearly show species-differences in response to hormones and AHR ligands between human and rat endometrial cells in vitro, which might greatly affect the applicability of the rat as translational model for human endometrial effects. This warrants further development of human relevant, endometrium-specific test methods for risk assessment purposes.

Original languageEnglish
Article number105458
Pages (from-to)1-9
Number of pages9
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume194
Early online date26 Aug 2019
DOIs
Publication statusPublished - 1 Nov 2019

Fingerprint

Endometrium
Coculture Techniques
Rats
Aryl Hydrocarbon Receptors
Gene expression
Cytochrome P-450 Enzyme System
Gene Expression
Hormones
Ligands
Poisons
Human Development
Periodicity
Progesterone Receptors
Metabolites
Estrogen Receptors
Risk assessment
Progesterone
Polychlorinated Dibenzodioxins
1,4-dioxin

Keywords

  • Aryl hydrocarbon receptor
  • Cytochrome P450 1A1
  • Endometrium
  • Hormone receptors

Cite this

van den Brand, A. D. ; Rubinstein, E. ; de Jong, P. C. ; van den Berg, M. ; van Duursen, M. B.M. / Primary endometrial 3D co-cultures : A comparison between human and rat endometrium. In: Journal of Steroid Biochemistry and Molecular Biology. 2019 ; Vol. 194. pp. 1-9.
@article{6e705cf9a6934af49551b0e5637a4e9b,
title = "Primary endometrial 3D co-cultures: A comparison between human and rat endometrium",
abstract = "Human and rat reproductive systems differ significantly with respect to hormonal cyclicity and endometrial cell behavior. However, species-differences in endometrial cell responses upon hormonal stimulation and exposure to potentially toxic compounds are poorly characterized. In this study, human and rat endometrial hormonal responses were assessed in vitro using a 3D co-culture model of primary human and rat endometrial cells. The models were exposed to the aryl hydrocarbon receptor (AHR) ligands 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), laquinimod, and its AHR active metabolite DELAQ. In both the human and rat endometrial models, estrogen receptor and progesterone receptor gene expression was modulated by the hormonal treatments, comparable to the in vivo situation. AHR gene expression in the human endometrial model did not change when exposed to hormones. In contrast, AHR expression decreased 2-fold in the rat model when exposed to predominantly progesterone, which resulted in a 2.8-fold attenuation of gene expression induction of cytochrome P450 1A1 (CYP1A1) by TCDD. TCDD and DELAQ, but not laquinimod, concentration-dependently induced CYP1A1 gene expression in both human and rat endometrial models. Interestingly, the relative degree of DELAQ to induce CYP1A1 was higher than that of TCDD in the human model, while it was lower in the rat model. These data clearly show species-differences in response to hormones and AHR ligands between human and rat endometrial cells in vitro, which might greatly affect the applicability of the rat as translational model for human endometrial effects. This warrants further development of human relevant, endometrium-specific test methods for risk assessment purposes.",
keywords = "Aryl hydrocarbon receptor, Cytochrome P450 1A1, Endometrium, Hormone receptors",
author = "{van den Brand}, {A. D.} and E. Rubinstein and {de Jong}, {P. C.} and {van den Berg}, M. and {van Duursen}, {M. B.M.}",
year = "2019",
month = "11",
day = "1",
doi = "10.1016/j.jsbmb.2019.105458",
language = "English",
volume = "194",
pages = "1--9",
journal = "Journal of Steroid Biochemistry and Molecular Biology",
issn = "0960-0760",
publisher = "Elsevier Limited",

}

Primary endometrial 3D co-cultures : A comparison between human and rat endometrium. / van den Brand, A. D.; Rubinstein, E.; de Jong, P. C.; van den Berg, M.; van Duursen, M. B.M.

In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 194, 105458, 01.11.2019, p. 1-9.

Research output: Contribution to JournalArticleAcademicpeer-review

TY - JOUR

T1 - Primary endometrial 3D co-cultures

T2 - A comparison between human and rat endometrium

AU - van den Brand, A. D.

AU - Rubinstein, E.

AU - de Jong, P. C.

AU - van den Berg, M.

AU - van Duursen, M. B.M.

PY - 2019/11/1

Y1 - 2019/11/1

N2 - Human and rat reproductive systems differ significantly with respect to hormonal cyclicity and endometrial cell behavior. However, species-differences in endometrial cell responses upon hormonal stimulation and exposure to potentially toxic compounds are poorly characterized. In this study, human and rat endometrial hormonal responses were assessed in vitro using a 3D co-culture model of primary human and rat endometrial cells. The models were exposed to the aryl hydrocarbon receptor (AHR) ligands 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), laquinimod, and its AHR active metabolite DELAQ. In both the human and rat endometrial models, estrogen receptor and progesterone receptor gene expression was modulated by the hormonal treatments, comparable to the in vivo situation. AHR gene expression in the human endometrial model did not change when exposed to hormones. In contrast, AHR expression decreased 2-fold in the rat model when exposed to predominantly progesterone, which resulted in a 2.8-fold attenuation of gene expression induction of cytochrome P450 1A1 (CYP1A1) by TCDD. TCDD and DELAQ, but not laquinimod, concentration-dependently induced CYP1A1 gene expression in both human and rat endometrial models. Interestingly, the relative degree of DELAQ to induce CYP1A1 was higher than that of TCDD in the human model, while it was lower in the rat model. These data clearly show species-differences in response to hormones and AHR ligands between human and rat endometrial cells in vitro, which might greatly affect the applicability of the rat as translational model for human endometrial effects. This warrants further development of human relevant, endometrium-specific test methods for risk assessment purposes.

AB - Human and rat reproductive systems differ significantly with respect to hormonal cyclicity and endometrial cell behavior. However, species-differences in endometrial cell responses upon hormonal stimulation and exposure to potentially toxic compounds are poorly characterized. In this study, human and rat endometrial hormonal responses were assessed in vitro using a 3D co-culture model of primary human and rat endometrial cells. The models were exposed to the aryl hydrocarbon receptor (AHR) ligands 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), laquinimod, and its AHR active metabolite DELAQ. In both the human and rat endometrial models, estrogen receptor and progesterone receptor gene expression was modulated by the hormonal treatments, comparable to the in vivo situation. AHR gene expression in the human endometrial model did not change when exposed to hormones. In contrast, AHR expression decreased 2-fold in the rat model when exposed to predominantly progesterone, which resulted in a 2.8-fold attenuation of gene expression induction of cytochrome P450 1A1 (CYP1A1) by TCDD. TCDD and DELAQ, but not laquinimod, concentration-dependently induced CYP1A1 gene expression in both human and rat endometrial models. Interestingly, the relative degree of DELAQ to induce CYP1A1 was higher than that of TCDD in the human model, while it was lower in the rat model. These data clearly show species-differences in response to hormones and AHR ligands between human and rat endometrial cells in vitro, which might greatly affect the applicability of the rat as translational model for human endometrial effects. This warrants further development of human relevant, endometrium-specific test methods for risk assessment purposes.

KW - Aryl hydrocarbon receptor

KW - Cytochrome P450 1A1

KW - Endometrium

KW - Hormone receptors

UR - http://www.scopus.com/inward/record.url?scp=85071577768&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85071577768&partnerID=8YFLogxK

U2 - 10.1016/j.jsbmb.2019.105458

DO - 10.1016/j.jsbmb.2019.105458

M3 - Article

VL - 194

SP - 1

EP - 9

JO - Journal of Steroid Biochemistry and Molecular Biology

JF - Journal of Steroid Biochemistry and Molecular Biology

SN - 0960-0760

M1 - 105458

ER -