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Effects of some endocrine disruptors on the proliferation and viability of human endometrial endothelial cells in vitro
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: Reproductive Toxicology, ISSN 0890-6238, E-ISSN 1873-1708, Vol. 23, no 4, 550-559 p.Article in journal (Refereed) Published
Abstract [en]

Endocrine disrupting chemicals (EDCs) pose a potential threat to human reproductive health. We studied the proliferation and viability of human endometrial endothelial cells (HEECs) in vitro after exposure to 2,2-bis(o,p-chlorophenyl)-1,1,1-trichloroethane (o,p′-DDT), 3,3′,4,4′-tetrachlorobiphenyl (CB 77), 3,3′,4,4′,5-pentachlorobiphenyl (CB 126), di-n-butyl phthalate (DBP), bisphenol A (BPA), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and 17β-oestradiol, progesterone, 17α-ethynyl oestradiol and levonorgestrel. Cell proliferation was studied using immunocytochemistry for PCNA expression and a 5-bromo-2′-deoxyuridine assay. Cell viability was studied by vital staining with propidium iodide and Hoechst 33258. HEECs in primary culture responded with increased proliferation to oestradiol and with decreased proliferation to levonorgestrel and the EDCs. Some EDCs also affected cell viability and increased the proportion of necrotic cells. However, the decrease in proliferation in response to DBP and TCDD cannot be explained by cell death. In light of these results, it is possible that the EDCs could have effects in vivo as well as in vitro, and influence processes involving for example endometrial angiogenesis.

Place, publisher, year, edition, pages
2007. Vol. 23, no 4, 550-559 p.
Keyword [en]
Endocrine disruptors, Human endometrial endothelial cells, o, p′-DDT, PCB 77, PCB 126, Di-n-butyl phthalate, Bisphenol A, TCDD
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-96510DOI: 10.1016/j.reprotox.2007.03.006ISI: 000247231000010PubMedID: 17493787OAI: oai:DiVA.org:uu-96510DiVA: diva2:171108
Available from: 2007-11-22 Created: 2007-11-22 Last updated: 2011-02-05Bibliographically 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.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 298
Keyword
Obstetrics and gynaecology, Reproductive toxicology, Baltic grey seal, leiomyoma, myometrial cells, endometrial endothelial cells, hormones, endocrine disruptors, Obstetrik och kvinnosjukdomar
Identifiers
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
Opponent
Supervisors
Available from: 2007-11-22 Created: 2007-11-22Bibliographically approved

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Bredhult, CarolinaOlovsson, Matts

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