A novel organotypic culture model for normal human endometrium: regulation of epithelial cell proliferation by estradiol and medroxyprogesterone acetate
Source: Human Reproduction, Volume 20, Number 4, April 2005 , pp. 864-871(8)
Publisher: Oxford University Press
Abstract:BACKGROUND: A novel organotypic culture system was established for modelling the hormonal responses of the normal human endometrium in vitro. METHODS: Endometrial epithelial cells were cultured as glandular organoids within reconstituted extracellular matrix (Matrigel) in tissue culture inserts and stromal cells on plastic below the epithelial compartment. The effects of estradiol (E<inf>2</inf>) and E<inf>2</inf> together with medroxyprogesterone acetate (MPA) on cell proliferation and the expression of estrogen receptor (ER) and progesterone receptor (PR) were studied in 10 epithelialstromal co-cultures and in three parallell monocultures of epithelial organoids. RESULTS: In co-cultures, E<inf>2</inf> was shown to increase the percentage of Ki67-positive cells by 2-fold relative to untreated controls. In the presence of MPA, a significant decrease in cell proliferation was detected. Similar results were obtained when the corresponding percentages of Ki67-positive organoids were calculated instead of individual cells. In the absence of stromal fibroblasts, Ki67 epithelial labelling remained below the control value after both hormonal treatments. Epithelial organoids retained their capacity to express estrogen and progesterone receptors in culture. E<inf>2</inf> was shown to markedly increase and MPA to down-regulate the expression of PR. The expression of ER was only slightly affected by either hormonal treatment. CONCLUSIONS: The present organotypic model provides a novel in vitro system in which to study the effects of steroids in the normal human endometrium both in terms of cell proliferation and gene expression. The culture system holds promise as a useful method to screen novel steroid compounds and may help to circumvent problems related to the use of animal models.
Document Type: Research article
Affiliations: 1: Department of Cell Biology, Medical School, 33014 University of Tampere, 2: Department of Obstetrics and Gynecology, Tampere University Hospital and 3: Department of Pathology, Centre for Laboratory Medicine, Tampere University Hospital, 33521Tampere, Finland
Publication date: 2005-04-01
- Human Reproduction features full-length, peer-reviewed papers reporting original research, clinical case histories, as well as opinions and debates on topical issues. Papers published cover the scientific and medical aspects of reproductive physiology and pathology, endocrinology, andrology, gonad function, gametogenesis, fertilization, embryo development, implantation, pregnancy, genetics, genetic diagnosis, oncology, infectious disease, surgery, contraception, infertility treatment, psychology, ethics and social issues. The highest scientific and editorial standard is maintained throughout the journal along with a rapid rate of publication.