RESUMEN
RNA-binding proteins (RBPs) have been described for cancer cell progression and differentiation, although there is still much to learn about their mechanisms. Here, using in vivo decidualization as a model, we describe the role of RBP cold shock domain containing C2 (CSDC2) in the endometrium. Csdc2 messenger RNA expression was differentially regulated depending on time and areas of decidua development, with the most variation in antimesometrium (AM) and, to a lesser degree, in the junctional zone (JZ). Immunohistochemistry of CSDC2 showed a preferentially cytoplasmic localization at AM and JZ, and nuclear localization in underneath myometrium and mesometrium (M). Cytoplasmic localization coincided with differentiated, DESMIN-marked areas, while nuclear localization coincides with proliferative zones. Uterine suppression of CSDC2 through intrauterine-injected-specific small interfering RNA (siRNA) led to abnormal decidualization in early pregnancy, with more extended antimesometrial area and with poor M development if compared with control siRNA-injected animals. These results suggest that CSDC2 could be a regulator during decidua development.
Asunto(s)
Diferenciación Celular/genética , Endometrio/crecimiento & desarrollo , Proteínas de Unión al ARN/genética , Animales , Respuesta al Choque por Frío/genética , Citoplasma/genética , Decidua/crecimiento & desarrollo , Implantación del Embrión/genética , Endometrio/metabolismo , Femenino , Humanos , Embarazo , Dominios Proteicos/genética , ARN Interferente Pequeño/genética , Ratas , Transducción de SeñalRESUMEN
In this study, we investigated whether neonatal exposure to a glyphosate-based herbicide (GBH) alters the reproductive performance and the molecular mechanisms involved in the decidualization process in adult rats. Newborn female rats received vehicle or 2 mg/kg/day of a GBH on postnatal days (PND) 1, 3, 5 and 7. On PND90, the rats were mated to evaluate (i) the reproductive performance on gestational day (GD) 19 and (ii) the ovarian steroid levels, uterine morphology, endometrial cell proliferation, apoptosis and cell cycle regulators, and endocrine pathways that regulate uterine decidualization (steroid receptors/COUP-TFII/Bmp2/Hoxa10) at the implantation sites (IS) on GD9. The GBH-exposed group showed a significant increase in the number of resorption sites on GD19, associated with an altered decidualization response. In fact, on GD9, the GBH-treated rats showed morphological changes at the IS, associated with a decreased expression of estrogen and progesterone receptors, a downregulation of COUP-TFII (Nr2f2) and Bmp2 mRNA and an increased expression of HOXA10 and the proliferation marker Ki67(Mki67) at the IS. We concluded that alterations in endometrial decidualization might be the mechanism of GBH-induced post-implantation embryo loss.
Asunto(s)
Glicina/análogos & derivados , Herbicidas/toxicidad , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Reproducción/fisiología , Animales , Animales Recién Nacidos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Decidua/efectos de los fármacos , Decidua/crecimiento & desarrollo , Endometrio/efectos de los fármacos , Endometrio/crecimiento & desarrollo , Femenino , Glicina/toxicidad , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Ratas , Reproducción/efectos de los fármacos , Útero/efectos de los fármacos , Útero/crecimiento & desarrollo , GlifosatoRESUMEN
Decidualization in the mouse consists of an extensive remodeling of the endometrial extracellular matrix, resulting in a reduction of the extracellular spaces, an increase in the diameter of collagen fibrils, and changes in the relative ratio of different types of glycosaminoglycans. To assess the dynamic changes of the endometrial extracellular matrix during decidualization, collagen was analyzed biochemically and immunochemically in the endometrium of nulliparous and day 5 to day 8 pregnant mice. The amount of collagen per gram dry weight was higher in the endometrium of implantation sites than in interimplantation sites. Collagen types I, III, and V were the main components of the endometrium of nulliparous and pregnant animals. The amount of collagen type V was higher in the endometrium of pregnant animals than in nulliparous ones. A relative unusual homotrimeric form of collagen type V, probably formed by [alpha1(V)](3), was detected in pregnant endometrium by gel eletrophoresis and immunoblotting.
Asunto(s)
Colágeno/metabolismo , Decidua/crecimiento & desarrollo , Decidua/metabolismo , Animales , Femenino , Hidroxiprolina/metabolismo , Ratones , Embarazo , Factores de TiempoRESUMEN
BACKGROUND: A decidual cell reaction can be induced in rodent endometrium by an intrauterine injection of oil. The epithelial lining is thought to be instrumental to transduce intralumenal stimuli for decidualization. One of the consequences of oil injection is the death of uterine epithelial cells. No information is available on the effect that sustained contact with oil has on the epithelium. METHODS: A decidual cell reaction was induced in 4-day pseudopregnant mice by injection of 30 microliters of arachis oil into the uterine lumen. Samples from the uteri were collected 24, 48, and 72 h after the injection and prepared for transmission electron microscopy. RESULTS: Twenty-four hours after the oil injection, some of the initial modifications of epithelial cell surfaces were very similar to those induced by the contact with the blastocyst during normal pregnancy. Uterine epithelial cells internalized injected oil and many cells were seen in various stages of degeneration. At 48 h, many epithelial cells were detached from the basal lamina. At 72 h, the uterine lining was re-established by flattened cells. CONCLUSIONS: The contact of oil with the uterine epithelium of pseudo pregnant mice induces epithelial cell death in the antimesometrial region of the uterine crypt. There is, however, replacement of epithelial lining by epithelial cells, which probably migrate from the mesometrial region of the crypt. The prolonged presence of oil within the uterine lumen seems to induce cycles of epithelial cell death and replacement.
Asunto(s)
Decidua/crecimiento & desarrollo , Endometrio/citología , Animales , Muerte Celular , División Celular , Femenino , Ratones , Microscopía Electrónica , Aceite de Cacahuete , Aceites de Plantas/administración & dosificación , Embarazo , Factores de TiempoRESUMEN
The localization of lipids in the endometrium of virgin and 6- to 9-day-pregnant mice was detected by histochemical methods. Total lipids (as shown by staining with Sudan black) and phospholipids containing choline (PCC) were detected. Sections subjected to reactions that have been proposed for the demonstration of vitamins E and D and cholesterol gave negative results. In the virgin animals, lipids were found in epithelial cells but not in the endometrial storma. On the other hand in the pregnant animals, the endometrial stroma contained both Sudan-black-stained lipids and PCC. Maximal staining was reached on day 8 of pregnancy. The staining was more conspicuous in the more differentiated decidual cells adjacent to the embryos than in the less differentiated predicidual cells. The nondecidualized stroma, situated peripherally near the myometrium did not stain for lipids. In the cytoplasm of decidual cells the reaction for PCC was observed in the form of granules, which were often arranged in groups surrounding the nuclei. We suggest that decidual cells store PCC to be mobilized as a precursor for mediators of decidualization, such as prostaglandins, that would act as paracrine inducers of the decidual reaction.