Biomedical subjects

R Grümmer

Publications and source records attributed to R Grümmer.

23 records · Page 2Linked to original sources

PubMed1996

Induction of connexin 32 expression by potential embryonic signals in rabbit uterine epithelium.

Connexin 32 induction is found in rabbit uterine epithelium as a response to embryo recognition. Here we have chosen this connexin 32 expression as a cell biological marker to define the type of a locally acting embryonic signal. 17 beta-estradiol, onapristone, catechol estrogen (4-hydroxy-estradiol), prostaglandins E2 and F2 alpha, db-cAMP, and glass beads as mechanical stimuli were given to pseudopregnant animals on day 4, 5 or 6 posthuman chorionic gonadotropin (hCG). The induction of connexin 32 corresponded to the time of implantation at days 6-8 post-hCG by immunohistochemistry and Northern blot analysis. Untreated pseudopregnant animals started to express connexin 32 on day 8 post-hCG. In animals treated with 4-hydroxy-estradiol, 17 beta-estradiol or prostaglandins, connexin 32 expression started 1 day earlier (day 7 post-hCG) and led to an enhanced connexin 32 expression on day 8 post-hCG compared to control animals. The antigestagen, onapristone, as well as cAMP did not alter the endogenous program. Mechanical stimuli led to a high expression of connexin 32 starting at day 7 post-hCG whereas in pregnancy the blastocyst induces connexin 32 expression from day 6 postcoitum onwards. Combination of mechanical stimuli with 17 beta-estrogen advanced the induction to day 6 post-hCG. We conclude that a mechanical stimulus in combination with 17 beta-estradiol induces connexin 32 synthesis in a similar manner as compared to the blastocyst during pregnancy.

Animals↗

PubMed1995

Expression of gap junction connexins in the human endometrium throughout the menstrual cycle.

Expression of connexins, the proteins which comprise gap junction channels, is regulated by ovarian hormones in the female reproductive tract of rodents. In order to determine if these hormones also affect connexin expression in the human uterus, the distribution patterns of different connexins (cx26, cx32, cx43) were investigated by immunohistochemistry in human endometrial tissue collected throughout the menstrual cycle. During the early proliferative phase of the cycle extremely low staining for connexin 43 was observed and connexin 26 antigens could not be detected. An increase in the amount of connexin 43 in stromal cells and of connexin 26 in glandular and luminal epithelial cells was seen from days 11-15 of the cycle. Following ovulation, the expression of both connexins was suppressed and was completely abolished in the late secretory phase. Weak staining for connexin 32 was found mainly in the late proliferative and the early secretory phase and was restricted to the basal membrane region of the glandular cells. These results suggest that the different connexins could represent cell biological markers for the proliferation and differentiation of the human endometrium throughout the menstrual cycle.

Connexin 26↗

PubMed1994

Adhesion and invasion of three human choriocarcinoma cell lines into human endometrium in a three-dimensional organ culture system.

A novel in vitro model was developed to study attachment and invasion of choriocarcinoma cell spheroids using pre-cultured secretory phase human endometrium as a host tissue. During pre-culturing in shaker culture human endometrium had regenerated a complete epithelial covering and had shed cells damaged during explantation. Spheroids of three human choriocarcinoma cell lines (BeWo, Jeg-3, JAr) which displayed linear growth in culture and produced placental hormones were used in this study as models for trophoblast behaviour. Morphological differences were noted in the spheroids from the three choriocarcinoma cell lines; BeWo and Jeg-3 spheroids exposed flattened and more differentiated cells on their surfaces while superficial cells in JAr spheroids maintained their cytotrophoblast-like morphology. Spheroids from all three cell lines were proven to be invasive in a general invasion assay using embryonic chick heart fragments, with JAr spheroids being the most aggressive. When spheroids were confronted with pre-cultured re-epithelialized endometrial fragments, however, Jeg-3 spheroids showed the highest incidence of attachment (52%) and the greatest amount of invasion into the underlying stroma. BeWo spheroids also attached (37%) and penetrated the epithelium, but did not invade into the stroma. JAr spheroids showed a minor degree of attachment (12%) and little or no invasion into the stroma. These results show that the three choriocarcinoma cell lines, although all invasive in a general invasion assay, differ in adhesion to uterine epithelium and invasion into endometrial stroma. This model offers opportunities for studying mechanisms of trophoblast adhesion and invasion, using human endometrium as the natural host tissue.

Animals↗

PubMed1994

Regulation of connexin26 and connexin43 expression in rat endometrium by ovarian steroid hormones.

A distinct spatial and temporal pattern of connexin26 and connexin43 (cx26 and cx43) expression was observed in the rat endometrium in response to embryo implantation; however, connexin expression was suppressed during the preimplantation period. Pseudopregnant rats did not show connexin mRNA, while artificial decidualization induced by a scratch led to a strong expression of cx26 and cx43 in the endometrium of these animals. In order to examine the regulatory effects of ovarian steroid hormones on connexin expression, ovariectomized rats were treated with progesterone (P) and/or estradiol-17 beta (E2). Untreated, ovariectomized animals expressed mRNA for cx43, but not for cx26. Endometrial expression of mRNA for both connexins was strongly enhanced by E2 treatment; immunolabeling revealed protein for cx26 in the uterine luminal epithelial cells and for cx43 in the uterine stromal cells. P treatment, either alone or in combination with E2, suppressed expression of connexin mRNA. P suppression in the presence of E2 was reversible when P was withdrawn. When administered on Days 0-2 of pregnancy, the antiprogestin onapristone inhibited the effect of P and gave rise to strong expression of both connexin transcripts. These results demonstrate that expression of cx26 and cx43 in the rat uterine endometrium is differentially regulated by E2 and P during early pregnancy.

Animals↗

PubMed1993

Spatial and temporal expression of connexin26 and connexin43 in rat endometrium during trophoblast invasion.

The expression of two different gap junction transcripts, connexin26 and connexin43, has been investigated in rat endometrium during implantation and early chorionic-allantoic placentation. An induction of connexin26 protein is detected locally in the epithelium of the implantation chamber prior to trophoblast invasion. At the same stage connexin43 is found exclusively in the primary decidual zone. By the sixth day of pregnancy the uterine epithelium of the implantation chamber has degenerated and the invading trophoblast is directly confronted with the developing decidua. Connexin26 is then detected in decidual cells accompanying the invading trophoblast, whereas connexin43 has spread through the decidual tissue up into the myometrial layers. This distribution pattern of connexin43 and connexin26 is maintained until at least Day 9 of pregnancy. In decidual cells adjacent to the trophoblast both connexins seem to be coexpressed in the same gap junctional plaque. In these early stages of pregnancy a clear correlation exists between levels of connexin43 mRNA and protein expression. In regard to connexin26 mRNA a similar correlation is found from Day 5 of pregnancy onward. The amount of mRNA on Day 4, however, does not correspond to the amount of connexin26 antigen in the endometrium at that stage. The spatial and temporal expression pattern of connexin26 accompanies the process of embryo implantation in the surrounding endometrium, pointing to a specialized function of these cells.

Animals↗