Global transcriptomic response of bovine endometrium to blastocyst-stage embryos.

The aims of this study were (i) to investigate changes in the global transcriptome of bovine endometrial explants induced by exposure to blastocysts, (ii) to investigate if male and female blastocysts elicit a differential response in the endometrial transcriptome in vitro and (iii) to determine whether bovine endometrium responds to the presence of murine embryos. In Experiment 1, endometrial explants from the same uterus were cultured for 6 h with or without 20 in vitro-produced bovine blastocysts. In Experiment 2, endometrial explants were cultured with male or female bovine blastocysts produced in vitro by IVF either using sex-sorted semen or conventional unsorted semen followed by embryo sexing based on a biopsy. In Experiment 3, endometrial explants were cultured alone or in the presence of bovine blastocysts (n = 25) or murine blastocysts (n = 25). Following culture, explants were snap frozen and stored at -80°C until RNA extraction, qPCR or RNA-Seq. Culture with bovine blastocysts increased endometrial expression of 40 transcripts, all of which were interferon-tau induced. Culture with male or female bovine blastocysts increased transcript abundance of five classic interferon-stimulated genes (MX1, MX2, ISG15, OASY1, RSAD2) in explants; however, there was no difference in abundance of transcripts previously reported to be related to embryonic sex (IFNAR1, IFNAR2, CTGF, ARTN, SLC2A1, SLC2A5). Exposure to murine blastocysts did not elicit any detectable change in transcript abundance. These findings, coupled with our previous data, indicate that very local, interferon-tau-induced changes in endometrial gene expression occur in response to blastocysts; whether such changes play any role in subsequent pregnancy recognition remains to be established.

Blastocyst-induced changes in the bovine endometrial transcriptome.

The objectives of this study were (i) to determine whether blastocyst-induced responses in endometrial explants were detectable after 6- or 24-h co-culture in vitro; (ii) to test if direct contact is required between embryos and the endometrial surface in order to stimulate endometrial gene expression; (iii) to establish the number of blastocysts required to elicit a detectable endometrial response; (iv) to investigate if upregulation of five interferon-stimulated genes (ISGs) in the endometrium was specific to the blastocyst stage and (v) to test if alterations in endometrial gene expression can be induced by blastocyst-conditioned medium. Exposure of endometrial explants to Day 8 blastocysts in vitro for 6 or 24 h induced the expression of ISGs (MX1, MX2, OAS1, ISG15, RSAD2); expression of IFNAR1, IFNAR2, NFKB1, IL1B, STAT1, LGALS3BP, LGALS9, HPGD, PTGES, ITGB1, AKR1C4, AMD1 and AQP4 was not affected. Culture of explants in the presence of more than five blastocysts was sufficient to induce the effect, with maximum expression of ISGs occurring in the presence of 20 blastocysts. This effect was exclusive to blastocyst stage embryos; oocytes, 2-cell embryos or Day 5 morulae did not alter the relative abundance of any of the transcripts examined. Direct contact between blastocysts and the endometrial surface was not required in order to alter the abundance of these transcripts and blastocyst-conditioned medium alone was sufficient to stimulate a response. Results support the notion that local embryo-maternal interaction may occur as early as Day 8 of pregnancy in cattle.

Effect of human chorionic gonadotrophin administration 2 days after insemination on progesterone concentration and pregnancy per artificial insemination in lactating dairy cows.

The aim of this study was to examine the effect of a single administration of human chorionic gonadotrophin (hCG) during the establishment of the corpus luteum (CL) on progesterone (P4) concentration and pregnancy per artificial insemination (P/AI) in lactating dairy cows. Postpartum spring-calving lactating dairy cows (n = 800; mean ± SD days in milk and parity were 78.5 ± 16.7 and 2.3 ± 0.8, respectively) on 3 farms were enrolled on the study. All cows underwent the same fixed-time AI (FTAI) protocol involving a 7-d progesterone-releasing intravaginal device with gonadotrophin-releasing hormone (GnRH) administration at device insertion, prostaglandin at device removal followed by GnRH 56 h later, and AI 16 h after the second GnRH injection. Cows were blocked on days postpartum, body condition score, and parity and randomly assigned to receive either 3,000 IU of hCG 2 d after FTAI or no further treatment (control). Blood samples were collected on d 7 and 14 postestrus by coccygeal venipuncture on a subset of 204 cows to measure serum P4 concentration, and pregnancy was diagnosed by ultrasonography approximately 30 and 70 d after FTAI. Administration of hCG caused an increase in circulating P4 concentrations compared with the control treatment on d 7 (+22.2%) and d 14 (+25.7%). The P/AI at 30 d after FTAI was affected by treatment, farm, body condition score, and calving to service interval. Overall, administration of hCG decreased P/AI (46.3% vs. 55.1% for the control). Among cows that did not become pregnant following AI, a greater proportion of control cows exhibited a short repeat interval (≤17 d) compared with cows treated with hCG (8.6% vs. 2.8%, respectively). In addition, the percentages of cows pregnant at d 21 (59.6% vs. 52.0%) and d 42 (78.3% vs. 71.9%) were greater in control than in hCG-treated cows. The overall incidence of embryo loss was 10.7% and was not affected by treatment. There was a tendency for an interaction between treatment and CL status at synchronization protocol initiation for both P4 concentration and P/AI. In conclusion, administration of hCG 2 d after FTAI increased circulating P4 concentrations. Unexpectedly, cows treated with hCG had lower fertility; however, this negative effect on fertility was manifested primarily in cows lacking a CL at the onset of the synchronization protocol.

Aurora B: a new prognostic marker and therapeutic target in cancer.

Aurora B is a serine-threonine kinase belonging to the highly conserved Aurora family of mitotic kinases. Aurora B is a chromosomal passenger protein involved in chromosome segregation, spindle-checkpoint, and cytokinesis. Alteration of each of these steps could induce aneuploidy, one of main features, and driving force of cancer progression. The overexpression of Aurora B has been observed in several tumor types, and has been linked with a poor prognosis of cancer patients. In this review we will focus on the role of Aurora B in cancer development, its role as a prognostic marker, and the clinical outcome of recently developed Aurora(s) inhibitors.