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Gene expression analysis of human endometrial endothelial cells exposed to o,p'-DDT
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. (Klinisk och experimentell reproduktionsbiologi/Olovsson)
2008 (English)In: Molecular human reproduction, ISSN 1360-9947, Vol. 14, no 2, 97-106 p.Article in journal (Refereed) Published
Abstract [en]

The endocrine disrupting chemical o, p'-dichlorodiphenyltrichloroethane (DDT) can affect reproductive organs, tissues and cells in several species. Treatment of human endometrial endothelial cells (HEECs) with 50 mu M o, p'0- DDT decreased their proliferation compared with the control. Microarray analyses revealed that o, p'-DDT affected biological processes such as the cell cycle, cell division, defence response and lipid and steroid metabolism, in cellular components such as the plasma membrane and chromosomes, with molecular functions involved in signalling, receptor and cytokine activity, confirming the results of the proliferation assay. Expression of five of the most differentially expressed genes identified in the microarray analysis was verified by real- time quantitative reverse transcription polymerase chain reaction in five HEEC cultures obtained from women in the proliferative phase and in five cultures obtained from women in the secretory phase of the menstrual cycle after treatment with o, p'- DDT. The present study supports our previous findings of decreased proliferation and increased cell death in response to o, p'- DDT and may offer important clues to the mechanisms of action of o, p'-DDT.

Place, publisher, year, edition, pages
2008. Vol. 14, no 2, 97-106 p.
Keyword [en]
endometrial cells, in vitro cell cultures, microarray, o, p'-DDT, reproductive tissue
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-96511DOI: 10.1093/molehr/gam091ISI: 000257148600004PubMedID: 18204070OAI: oai:DiVA.org:uu-96511DiVA: diva2:171109
Available from: 2007-11-22 Created: 2007-11-22 Last updated: 2009-10-29Bibliographically approved
In thesis
1. Effects of some Endocrine Disruptors on Human and Grey Seal Uterine Cells
Open this publication in new window or tab >>Effects of some Endocrine Disruptors on Human and Grey Seal Uterine Cells
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The effects of environmental contaminants in humans and animals are of great concern. Some contaminants are endocrine disruptors that may interfere with the endogenous hormonal signalling and disturb, for example, reproductive organs and functions.

Primary uterine myometrial cells originating from women and Baltic grey seals were exposed to some polychlorinated biphenyls (PCBs) and their metabolites. Even though human and Baltic grey seal myometrial cells responded differently to the tested PCBs, the results indicate that PCBs can influence myometrial cell proliferation in vitro.

The prevalence of uterine leiomyomas was investigated among 257 Baltic grey seals. Leiomyomas were only present in females older than 22 years, at a prevalence of 65%. Proliferation in leiomyoma cells was detected in individuals lacking ovarian proliferation support, suggesting the presence of an exogenous stimulant. By taking into account temporal alterations in the contaminant burden of the seals, PCB exposure was found to be associated with leiomyoma prevalence. In conclusion, PCB exposure may be related to uterine leiomyoma development and proliferation in Baltic grey seals in vivo.

Human endometrial endothelial cells (HEECs) were exposed to some endocrine disruptors, and the effects of the endocrine disruptors on cell proliferation and viability were studied. All evaluated endocrine disruptors decreased HEEC proliferation and most also decreased HEEC viability. Further studies revealed that the reduction in HEEC proliferation after exposure to o,p’-DDT was associated with differential expression of mRNA involved in proliferation, defence response, and lipid and cholesterol metabolism compared to untreated HEEC.

In conclusion, these studies suggest that endocrine disruptors affect cultured cells from the female reproductive tract of humans and grey seals, and may have deleterious effects on proliferation, viability, and genes involved in defence response, and lipid or cholesterol metabolism.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2007. 105 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 298
Obstetrics and gynaecology, Reproductive toxicology, Baltic grey seal, leiomyoma, myometrial cells, endometrial endothelial cells, hormones, endocrine disruptors, Obstetrik och kvinnosjukdomar
urn:nbn:se:uu:diva-8334 (URN)978-91-554-7041-8 (ISBN)
Public defence
2007-12-14, Rosénsalen, Department of Women's and Children's Health, Uppsala University Hospital entrance 95/96, 09:15
Available from: 2007-11-22 Created: 2007-11-22Bibliographically approved

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