Feto-maternal communication in the dog involves the differentiation of stromal cells into decidual cells. As the only placental cells expressing the nuclear progesterone (P4) receptor (PGR), decidual cells play crucial roles in the maintenance and termination of pregnancy. Accordingly, to investigate possible PGR-mediated mechanisms in canine decidual cells, in vitro decidualized dog uterine stromal (DUS) cells were treated with functional PGR-blockers, mifepristone and aglepristone. Effects on decidualization markers, epithelial and mesenchymal factors, and markers of cellular viability were assessed. Decidualization increased the expression of PTGES, PGR, IGF1, and PRLR, along with ECM1, COL4 and CX43, but downregulated IGF2. DUS cells retained their mesenchymal character, and the expression of COL4 indicated the mesenchymal-epithelial transformation. Antigestagen treatment decreased the availability of PTGES, PRLR, IGF1 and PGR. Furthermore, antigestagens decreased the mRNA and protein expression of CX43, and transcriptional levels of ECM1 and COL4. Additionally, antigestagens increased levels of activated-CASP3 (a proapoptotic factor), associated with lowered levels of PCNA (a proliferation marker). These data reveal important aspects of the functional involvement of PGR in canine decidual cells, regarding the expression of decidualization markers and acquisition of epithelial-like characteristics. Some of these mechanisms may be crucial for the maintenance and/or termination of canine pregnancy.
Background: Benefits and harms of screening mammography have been disputed in recent years. This fact, along with the limitations of mammography as well as its unavailability in all our medical centers, tempted us to evaluate the accuracy of thermography in detecting breast abnormalities. Patients and Methods: All patients who were candidates for breast biopsy were examined by both mammography and thermography before tissue sampling in a referral center between January 2013 and January 2014. We defined sensitivities and specificities, and positive predictive values (PPVs) and negative predictive values (NPVs), of the 2 modalities in comparison with histologic results as the gold standard. Results: 132 patients were included. The median age of all patients was 49.5 ± 10.3 years (range 24-75 years). The sensitivity, specificity, PPV, NPV, and accuracy for mammography were 80.5%, 73.3%, 85.4%, 66.0%, and 76.9%, respectively, whereas for thermography the figures were 81.6%, 57.8%, 78.9%, 61.9%, and 69.7%, respectively. Conclusion: Our study confirms that, at the present time, thermography cannot substitute for mammography for the early diagnosis of breast cancer.
In the domestic dog placentation arises from central implantation, passing through a transitional, yet important stage of choriovitelline placenta (yolk sac placenta), on the way to the formation of the definite, deciduate, zonary (girdle) allantochorionic endotheliochorial placenta. Sharing some similarities with other invasive types of placentation, e.g. by revealing decidualization, it is characterized by restricted (shallow) invasion of trophoblast not affecting maternal capillaries and maternal decidual cells. Thus, being structurally and functionally placed between non-invasive epitheliochorial placentation and the more invasive hemochorial type, it presents an interesting and important model for understanding the evolutionarily determined aspects of mammalian placentation. More profound insights into the biological mechanisms underlying the restricted invasion of the fetal trophoblast into maternal uterine structures and the role of decidual cells in that process, could provide better understanding of some adverse conditions occurring in humans, like preeclampsia or placenta accreta. As an important endocrine organ actively responding to ovarian steroids and producing its own hormones, e.g. serving as the source of gestational relaxin or prepartum prostaglandins, the canine placenta has become an attractive research target, both in basic and clinical research. In particular the placental feto-maternal communication between maternal stroma-derived decidual cells and fetal trophoblast cells (i.e. an interplay between placenta materna and placenta fetalis) during the maintenance and termination of canine pregnancy, serves as an interesting model for induction of parturition in mammals and is an attractive subject for translational and comparative research. Here, an updated view on morpho-functional aspects associated with canine placentation is presented.
Maternal-stroma derived decidual cells, the only cell population in the canine placenta expressing the nuclear progesterone (P4) receptor (PGR), are crucial for the maintenance of canine pregnancy. Decreased circulating progesterone (P4) levels, or blockage of PGR function with antigestagens, terminate canine pregnancy. As an in vitro model for canine decidualization, dog uterine stromal (DUS) cells can be decidualized in vitro with cAMP. The antigestagens aglepristone and mifepristone ablate the expression of decidualization markers in DUS cells (e.g., PGR, PRLR, IGF1 or PTGES). Here, the transcriptome profile of DUS cells was investigated to acquire deeper insights into decidualization-associated changes. Additionally, effects mediated by antigestagens (competitive PGR blockers) in decidualized cells were assessed. Decidualization led to the upregulation of 1841 differentially expressed genes (DEGs, P and FDR < 0.01) involved in cellular proliferation and adhesion, mesenchymal-epithelial transition, extracellular matrix organization, and vaso- and immunomodulation. The 1475 DEGs downregulated after decidualization were mostly associated with apoptosis and cell migration. In decidualized DUS cells, aglepristone modulated 1400 DEGs and mifepristone 1558 DEGs. Interestingly, around half of the identified DEGs were modulated by only one of the antigestagens. In all cases, however, PGR-blockage was mainly associated with an inversion of several decidualization-induced effects. Comparison between antigestagen-mediated effects and transcriptional changes in the canine placenta at term allowed the identification of 191 DEGs associated with diminished cell proliferation and adhesion, and vascular and immune modulation. This study emphasizes the importance of P4/PGR signaling for decidual cell function, providing new insights into the maintenance of canine pregnancy.
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