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Effects of chlorinated biphenyls and metabolites on human uterine myocyte proliferation
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. (Klinisk och experimentell reproduktionsbiologi/Olovsson)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. (Klinisk och experimentell reproduktionsbiologi/Olovsson)
2007 (English)In: Human and Experimental Toxicology, ISSN 0960-3271, Vol. 26, no 10, 801-809 p.Article in journal (Refereed) Published
Abstract [en]

Uterine myometrial cells are responsive to sex steroids, which could make them susceptible to actions of endocrine disrupting environmental contaminants such as some PCBs. The aim of this investigation was to identify possible effects of some chlorinated biphenyls (CBs) and their metabolites on myometrial cell proliferation. Myometrial cells obtained from women in both phases of the menstrual cycle and from pregnant women were grown in vitro and exposed to CB 101, CB 118, 3'-MeSO2-CB 101, 4'-MeSO2-CB 101, 4-OH-CB 107, 17 beta-estradiol, progesterone, ethinylestradiol or levonorgestrel. The proliferative activity was studied by a BrdU assay. Myometrial cell cultures originating from pregnant women exhibited decreased proliferation in response to 3'-MeSO2-CB 101, 4'-MeSO2-CB 101 and 4-OH-CB 107. Estradiol, a combination of 1 nM 17 beta-estradiol and 10 nM progesterone, ethinylestradiol and levonorgestrel also reduced the proliferation of the myometrial cells, regardless of whether the cells were collected from either of the menstrual cycle phases or from pregnant women. To our knowledge this study is the first to demonstrate that some CBs affect the proliferative activity of human uterine myocytes.

Place, publisher, year, edition, pages
2007. Vol. 26, no 10, 801-809 p.
Keyword [en]
CB, in vitro, myometrial cells, PCB, proliferation, reproductive tissue
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-96508DOI: 10.1177/0960327107084534ISI: 000251684200005PubMedID: 18025052OAI: oai:DiVA.org:uu-96508DiVA: diva2:171106
Available from: 2010-03-18 Created: 2007-11-22 Last updated: 2010-04-14Bibliographically 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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