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

Published on Nov 1, 2019in The Journal of Steroid Biochemistry and Molecular Biology4.294
路 DOI :10.1016/J.JSBMB.2019.105458
A.D. van den Brand2
Estimated H-index: 2
(UU: Utrecht University),
E. Rubinstein2
Estimated H-index: 2
+ 2 AuthorsM.B.M. van Duursen2
Estimated H-index: 2
(VU: VU University Amsterdam)
Sources
Abstract
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.
馃摉 Papers frequently viewed together
References50
Newest
#1Samantha C Faber (UC Davis: University of California, Davis)H-Index: 2
#2Anatoly A. Soshilov (UC Davis: University of California, Davis)H-Index: 18
Last. Michael S. Denison (UC Davis: University of California, Davis)H-Index: 67
view all 5 authors...
The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that modulates gene expression following its binding and activation by structurally diverse chemicals. Species differences in AhR functionality have been observed, with the mouse AhR (mAhR) and human AhR (hAhR) exhibiting significant differences in ligand binding, coactivator recruitment, gene expression and response. While the AhR agonist indirubin (IR) is a more potent activator of hAhR-dependent gene expression tha...
Source
#1Maddalena Mallozzi (Sapienza University of Rome)H-Index: 11
#2C Leone (Sapienza University of Rome)H-Index: 3
Last. Donatella Caserta (Sapienza University of Rome)H-Index: 29
view all 5 authors...
Background: Although exposure to endocrine disruptor compounds (EDCs) has been suggested as a contributing factor to a range of women鈥檚 health disorders including infertility, polycystic ovaries and the early onset of puberty, considerable challenges remain in attributing cause and effect on gynaecological cancer. Until recently, there were relatively few epidemiological studies examining the relationship between EDCs and endometrial cancer, however, in the last years the number of these studies...
Source
#1Kaylon L. Bruner-Tran (Vandy: Vanderbilt University)H-Index: 32
#2Juan S. Gnecco (Vandy: Vanderbilt University)H-Index: 11
Last. Kevin G. Osteen (Vandy: Vanderbilt University)H-Index: 55
view all 6 authors...
Humans and other animals are exposed to a wide array of man-made toxicants, many of which act as endocrine disruptors that exhibit differential effects across the lifespan. In humans, while the impact of adult exposure is known for some compounds, the potential consequences of developmental exposure to endocrine disrupting chemicals (EDCs) is more difficult to ascertain. Animal studies have revealed that exposure to EDCs prior to puberty can lead to adult reproductive disease and dysfunction. Sp...
Source
The aryl hydrocarbon receptor is best known for its ability to mediate the toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, AHR plays important roles in the immune system, cell growth and numerous other cell functions. Similar to other transcription factors, tight control of AHR activity is necessary to prevent its over-activation. The AHR target gene, TCDD-inducible poly-ADP-ribose polymerase (TIPARP) was recently reported to be part of a new negative feedback loop that reg...
Source
Laquinimod is an oral drug currently being evaluated for the treatment of relapsing, remitting, and primary progressive multiple sclerosis and Huntington鈥檚 disease. Laquinimod exerts beneficial activities on both the peripheral immune system and the CNS with distinctive changes in CNS resident cell populations, especially astrocytes and microglia. Analysis of genome-wide expression data revealed activation of the aryl hydrocarbon receptor (AhR) pathway in laquinimod-treated mice. The AhR pathway...
Source
#1J.C. Paredes Palma (Institute for Social Security and Services for State Workers)H-Index: 1
#2C. Paredes Palma (Institute for Social Security and Services for State Workers)H-Index: 1
Last. V. Moreira ArmandoH-Index: 1
view all 7 authors...
Abstract Background Hysteroscopy is a clinical procedure that allows a gynecologist to see inside the uterus through endoscopy. This can be done for diagnosis or treatment of intrauterine conditions and as a method of surgery. Purpose To establish the prevalence of uterine disease in a group of healthy patients who underwent hysteroscopy as part of their gynecological examination. Materials and methods It was an observational study. 18 patients who attended a regular consultation provided by the...
Source
#1Philippe KoninckxH-Index: 61
#2Anastasia Ussia (UCSC: Catholic University of the Sacred Heart)H-Index: 11
Last. Leila Adamyan (Moscow State University of Medicine and Dentistry)H-Index: 14
view all 5 authors...
Endometriosis is known as a cause of pelvic pain and infertility. The epidemiology of endometriosis is important since the prevalence and severity of endometriosis might be linked to pollution and to our modern lifestyle, comprising food intake, chemical disruptors, postponement of the first pregnancy, and stress, as indicated by 鈥渁 career women鈥檚 disease.鈥 Epidemiological data based upon hospital discharge records should be viewed with caution. Indeed, that subtle lesions are considered patholo...
Source
#1M.A. Mart铆nez-Zamora (University of Barcelona)H-Index: 5
#2L. Mattioli (CSIC: Spanish National Research Council)H-Index: 2
Last. Francesc Carmona (University of Barcelona)H-Index: 16
view all 9 authors...
STUDY QUESTION: Are the levels of biologically active and the most toxic dioxin-like substances in adipose tissue of patients with deep infiltrating endometriosis (DIE) higher than in a control gro ...
Source
#1Felicitas Rataj (TUD: Dresden University of Technology)H-Index: 4
#2Frank Josef M枚ller (TUD: Dresden University of Technology)H-Index: 11
Last. Georg Kretzschmar (TUD: Dresden University of Technology)H-Index: 17
view all 7 authors...
Several studies indicate that the aryl hydrocarbon receptor (AHR), which plays an important role in mediating the toxicity of many industrial chemicals, plays an important role in the physiology of female reproductive tract organs. This makes it likely that the AHR and additional components of the AHR signalling pathway are under the control of female sex steroids. In a previous study, we could already demonstrate the regulation of many members of the AHR battery by 17尾-estradiol (E2) in the ute...
Source
#1Olivier Sorg (University of Geneva)H-Index: 26
Dioxins are a family of molecules associated to several industrial accidents such as Ludwigshafen in 1953 or Seveso in 1976, to the Agent Orange used during the war of Vietnam, and more recently to the poisoning of the former president of Ukraine, Victor Yushchenko. These persistent organic pollutants are by-products of industrial activity and bind to an intracellular receptor, AhR, with a high potency. In humans, exposure to dioxins, in particular 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) indu...
Source
Cited By4
Newest
#1Komodo Matta (INRA: Institut national de la recherche agronomique)H-Index: 3
#2Meriem Koual (French Institute of Health and Medical Research)H-Index: 5
Last. German Cano-Sancho (INRA: Institut national de la recherche agronomique)H-Index: 25
view all 8 authors...
Background: Growing epidemiological evidence suggests that organochlorine chemicals (OCCs), including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), may play a role in the pathogenesis of endometriosi...
Source
#1A.D. van den Brand (UU: Utrecht University)H-Index: 2
#2E. RubinsteinH-Index: 2
Last. Mbm van Duursen (VU: VU University Amsterdam)H-Index: 1
view all 5 authors...
Abstract Unopposed estrogenic action in the uterus can lead to the development of endometrial cancer in both humans and rats. Aryl hydrocarbon receptor (AHR) activation gives rise to anti-estrogenic actions and may consequently reduce the development of endometrial cancer. In this study, the anti-estrogenic potential of the AHR ligands 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and DELAQ, a metabolite of the pharmaceutical laquinimod, was assessed in in primary human and rat endometrial epitheli...
Source
#1J. FelgueirasH-Index: 1
#2Ricardo RibeiroH-Index: 9
Last. Pedro F. CostaH-Index: 16
view all 4 authors...
Abstract Infertility is a growing issue in modern society, being the fifth highest serious global disability according to the World Health Organization. To study infertility and other reproductive system complications, bench science still relies on 2D and animal studies, which regularly have been criticized due to their inability to mimic the human body. Particular challenges in 2D studies include the inability to mimic fluid dynamics, gametes modulation and their crosstalk, hormonal patterns as...
Source
#1Shanmugam Muruganandan (Harvard University)H-Index: 1
#2Xiujun Fan (CAS: Chinese Academy of Sciences)H-Index: 16
Last. Nihar R. Nayak (WSU: Wayne State University)H-Index: 26
view all 4 authors...
The human endometrium undergoes sequential phases of shedding of the upper functionalis zone during menstruation, followed by regeneration of the functionalis zone from the remaining basalis zone cells, and secretory differentiation under the influence of the ovarian steroid hormones estradiol (E2) and progesterone (P4). This massive tissue regeneration after menstruation is believed to arise from endometrial stromal and epithelial stem cells residing in the basal layer of the endometrium. Altho...
Source
This website uses cookies.
We use cookies to improve your online experience. By continuing to use our website we assume you agree to the placement of these cookies.
To learn more, you can find in our Privacy Policy.