Initiation and maintenance of pregnancy are critically dependent on an intact embryo-maternal communication in the preimplantation period. To get new insights into molecular mechanisms underlying this complex dialog, a holistic transcriptome study of endometrium samples from Day 18 pregnant vs. nonpregnant twin cows was performed. This genetically defined model system facilitated the identification of specific conceptus-induced changes of the endometrium transcriptome. Using a combination of subtracted cDNA libraries and cDNA array hybridization, 87 different genes were identified as upregulated in pregnant animals. Almost one half of these genes are known to be stimulated by type I interferons. For the ISG15ylation system, which is assumed to play an important role in interferon tau (IFNT) signaling, mRNAs of four potential components (IFITM1, IFITM3, HSXIAPAF1, and DTX3L) were found at increased levels in addition to ISG15 and UBE1L. These results were further substantiated by colocalization of these mRNAs in the endometrium of pregnant animals shown by in situ hybridization. A functional classification of the identified genes revealed several different biological processes involved in the preparation of the endometrium for the attachment and implantation of the embryo. Specifically, elevated transcript levels were found for genes involved in modulation of the maternal immune system, genes relevant for cell adhesion, and for remodeling of the endometrium. This first systematic study of maternal transcriptome changes in response to the presence of an embryo on Day 18 of pregnancy in cattle is an important step toward deciphering the embryo-maternal dialog using a systems biology approach.
Over the last decade, studies have begun to shed light on the distribution and genetic characterization of Echinococcus multilocularis, the causative agent of alveolar echinococcosis (AE), in North America. Recent findings indicate that the parasite is likely expanding its range in the central region of the United States and Canada and that invasions of European strains might have occurred. In our review, we present the available data on E. multilocularis infections in wild and domestic animals and humans in North America and emphasize the lack of knowledge on the distribution of the parasite in wild and domestic hosts. Furthermore, we stress the need to better understand the complexity of host communities and their roles in shaping the transmission and distribution of the parasite. We hypothesize that a lack of knowledge about AE by North American physicians might result in the misdiagnosis of cases and an underestimation of disease incidence. The endemic presence of the parasite in urban areas and a recent human case in Alberta, Canada, suggest that the scientific community may need to reconsider the local public health risks, re-assess past cases that might have been overlooked and increase surveillance efforts to identify new cases of human AE.
Establishment and maintenance of pregnancy are critically dependent on embryo-maternal communication during the preimplantation period. The horse is one of the few domestic species in which the conceptus-derived pregnancy recognition signal has not been identified. To gain new insights into the factors released by the equine conceptus, transcriptional profiling analyses of conceptuses retrieved 8, 10, 12, and 14 days after ovulation were performed using a whole-genome microarray. Selected array data were confirmed using quantitative PCR, and the expression of proteins of interest was confirmed using immunohistochemistry and Western blotting. Gene ontology classification of differentially regulated transcripts underlines the ongoing embryo-maternal dialogue. Transcript showing higher expression levels as conceptus' development proceeds mainly localizes to the extracellular environment, thereby having the potential to act upon the uterine environment. Genes involved in the positive regulation of the immune system are enriched among transcripts displaying decreased expression, reflecting the need of the semiallograft conceptus to be protected from the immune system. A subset of differentially expressed genes, such as BRCA1 and FGF2, has previously been described to be expressed by early stages of embryonic development, whereas other transcripts are apparently unique to equine conceptuses, as their expression has not been reported in other species. These transcripts include fibrinogen subunits, the expressions of which were confirmed at the mRNA and protein level. Furthermore, results indicate the counteraction of trophoblast invasion, and that the conceptus appears to regulate changes in sialic acid content of its capsule, an event suggested to be essential for successful establishment of pregnancy.
Establishment and maintenance of pregnancy are critically dependent on embryo-maternal communication during the preimplantation period. To gain new insights into this complex process in the horse, transcriptional profiling of Day 13.5 pregnant and cyclic endometrial tissue samples was carried out using custom-designed microarrays. Selected array data were validated using quantitative RT-PCR, and proteins of interest were localized using immunohistochemistry. One hundred and six transcripts were up-regulated, whereas 47 transcripts showed lower expression levels in pregnant mares, that is, were down-regulated in pregnant mares. Half of the genes with known or inferred function are classically regulated by estrogens. Elevated transcript levels were found for genes involved in cell-cell signaling, heat shock response, and secretory proteins, among others. Solute carrier family 36 (proton/amino acid symporter), member 2, SLC36A2, was one of the most highly up-regulated genes, potentially reflecting the nutritional needs of the rapidly developing embryo. Among the genes showing lower expression in pregnant mares, estrogen receptor 1 was of particular interest because of its potential involvement in the initiation of luteolysis in cyclic mares. We hypothesize that either conceptus' estrogens or luteinizing hormone of uterine origin is involved in the observed down-regulation of estrogen receptor 1. Several of the genes identified in the current study are known to play a role in early pregnancy in species other than the horse. Thus, products of these commonly expressed genes likely contain universal activities for controlling endometrial receptivity to the conceptus, whereas other factors play unique roles within specific species in ensuring ongoing corpus luteum function. This is the first systematic study of endometrial transcriptome changes in response to the presence of an embryo during maternal recognition of pregnancy and an important step toward deciphering the embryo-maternal dialogue in equids.
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