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Proliferative Effects of Estradiol, Progesterone, and Two CB Congeners and Their Metabolites on Gray Seal (Halichoerus grypus) Uterine Myocytes in Vitro
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
2003 (English)In: Toxicological Sciences, ISSN 1096-6080, E-ISSN 1096-0929, Vol. 75, no 1, 154-160 p.Article in journal (Refereed) Published
Abstract [en]

Gray seal females living in the Baltic Sea have been found to exhibit a high prevalence of uterine leiomyomas. These animals are also known to accumulate lipid-soluble PCBs in their blubber. PCBs have documented endocrine-disrupting effects; to investigate whether the PCBs could be part of the genesis of uterine smooth muscle tumors in this species, gray seal myometrial cell cultures were exposed to two CBs and their metabolites, as well as to estradiol and progesterone, after which the effects were analyzed in terms of proliferative activity by measurements of BrdU absorbance and protein content. Progesterone was found to have an inhibitory effect, whereas one CB acted as a stimulant on the myometrial cell proliferation. One of the CB metabolites also seemed to have an inhibitory effect, although this could not be statistically verified. These results suggest that some CBs have effects on uterine myometrial cell proliferation in gray seals and, thus, may also take part in the growth regulation of uterine leiomyomas.

Place, publisher, year, edition, pages
2003. Vol. 75, no 1, 154-160 p.
National Category
Clinical Medicine
URN: urn:nbn:se:uu:diva-96507DOI: 10.1093/toxsci/kfg161PubMedID: 12805643OAI: oai:DiVA.org:uu-96507DiVA: diva2:171105
Available from: 2007-11-22 Created: 2007-11-22 Last updated: 2016-02-10Bibliographically 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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