Cases of RhD variants RhD*DAU2/DAU6 and RhD*weak D type 4.1 in pregnant women in Saudi Arabia.

The D antigen is one of the most immunogenic and clinically significant antigens of the Rh blood group system due to its various genotypes that encode for more than 450 different variants. Accurate RhD typing and D variant identification is crucial specially in prenatal screening during pregnancy. Women with RhD -ve phenotype are eligible to Rh immune globulin (RhIG) prophylaxis for the prevention of anti-D alloimmunization and hemolytic disease of the fetus and newborn (HDFN). However, there are some women who possess RhD variant alleles, who are mistakenly grouped as RhD positive and considered not eligible for RhIG prophylaxis, putting them at risk of anti-D alloimmunization and consequently leading to HDFN during subsequent pregnancies. Here, we describe  two cases of RhD variants DAU2/DAU6 and Weak D type 4.1 in obstetric patients who were grouped as RhD +ve with negative antibody screening during routine serologic  testing. Weak/Partial D molecular analysis using genomic DNA Red Cell Genotyping (RCG) revealed that both patients had RhD variants, one of which DAU2/DAU6 allele associated with anti-D alloimmunization. According to routine testing neither patients received RhIG or transfusion. In this case report we document to our knowledge the first reported cases of RhD variants among pregnant women in Saudi Arabia.

The role of progesterone receptor isoforms in the myometrium.

Myometrial contraction is stringently controlled throughout pregnancy and parturition. Progesterone signaling, effecting through the progesterone receptor (PR), is pivotal in modulating uterine activity. Evidence has shown that two major PR isoforms, PR-A and PR-B, have distinct activities on gene regulation, and the ratio between these isoforms determines the contractility of the myometrium at different gestational stages. Herein, we focus on the regulation of PR activity in the myometrium, especially the differential actions of the two PR isoforms, which maintain uterine quiescence during pregnancy and regulate the switch to a contractile state at the onset of labor. To demonstrate the PR regulatory network and its mechanisms of actions on myometrial activity, we summarized the findings into three parts: Regulation of PR Expression and Isoform Levels, Progesterone Receptor Interacting Factors, and Biological Processes Regulated by Myometrial Progesterone Receptor Isoforms. Recent genomic and epigenomic data, from human specimens and mouse models, are recruited to support the existing knowledge and offer new insights and future directions in myometrial biology.

Uterine Deletion of Bmal1 Impairs Placental Vascularization and Induces Intrauterine Fetal Death in Mice.

Recently, it was demonstrated that the expression of BMAL1 was decreased in the endometrium of women suffering from recurrent spontaneous abortion. To investigate the pathological roles of uterine clock genes during pregnancy, we produced conditional deletion of uterine Bmal1 (cKO) mice and found that cKO mice could receive embryo implantation but not sustain pregnancy. Gene ontology analysis of microarray suggested that uterine NK (uNK) cell function was suppressed in cKO mice. Histological examination revealed the poor formation of maternal vascular spaces in the placenta. In contrast to WT mice, uNK cells in the spongiotrophoblast layer, where maternal uNK cells are directly in contact with fetal trophoblast, hardly expressed an immunosuppressive NK marker, CD161, in cKO mice. By progesterone supplementation, pregnancy could be sustained until the end of pregnancy in some cKO mice. Although this treatment did not improve the structural abnormalities of the placenta, it recruited CD161-positive NK cells into the spongiotrophoblast layer in cKO mice. These findings indicate that the uterine clock system may be critical for pregnancy maintenance after embryo implantation.

Extracellular vesicle microRNA in early versus late pregnancy with birth outcomes in the MADRES study.

Circulating miRNA may contribute to the development of adverse birth outcomes. However, few studies have investigated extracellular vesicle (EV) miRNA, which play important roles in intercellular communication, or compared miRNA at multiple time points in pregnancy. In the current study, 800 miRNA were profiled for EVs from maternal plasma collected in early (median: 12.5 weeks) and late (median: 31.8 weeks) pregnancy from 156 participants in the MADRES Study, a health disparity pregnancy cohort. Associations between miRNA and birth weight, birth weight for gestational age (GA), and GA at birth were examined using covariate-adjusted robust linear regression. Differences by infant sex and maternal BMI were also investigated. Late pregnancy measures of 13 miRNA were associated with GA at birth (PFDR<0.050). Negative associations were observed for eight miRNA (miR-4454+ miR-7975, miR-4516, let-7b-5p, miR-126-3p, miR-29b-3p, miR-15a-5p, miR-15b-5p, miR-19b-3p) and positive associations for five miRNA (miR-212-3p, miR-584-5p, miR-608, miR-210-3p, miR-188-5p). Predicted target genes were enriched (PFDR<0.050) in pathways involved in organogenesis and placental development. An additional miRNA (miR-107), measured in late pregnancy, was positively associated with GA at birth in infants born to obese women (PFDR for BMI interaction = 0.011). In primary analyses, the associations between early pregnancy miRNA and birth outcomes were not statistically significant (PFDR≥0.05). However, sex-specific associations were observed for early pregnancy measures of 37 miRNA and GA at birth (PFDR for interactions<0.050). None of the miRNA were associated with fetal growth measures (PFDR≥0.050). Our findings suggest that EV miRNA in both early and late pregnancy may influence gestational duration.

Gestação em idade avançada e aconselhamento genético: um estudo em torno das concepções de risco / Advanced maternal age pregnancy and genetic counseling: a study on the concept of risk

Resumo As inovações científicas em torno do estudo de cromossomos humanos surgidas após a segunda metade do século XX consolidaram a inserção da genética na assistência em saúde, no que tange ao diagnóstico pré-natal. A associação entre idade materna e síndromes genéticas, proposta por pesquisadores da biomedicina, produziu determinações sobre risco, referidas a gestantes a partir de determinada idade. O artigo apresenta as concepções de risco em torno do que a biomedicina considera ser idade materna avançada de modo a configurar o que é classificado como gestação de risco. A análise documental em manuais médicos brasileiros e estrangeiros das especialidades obstetrícia e genética evidenciou diferentes concepções de risco em relação ao fator etário reprodutivo. A idade materna é um aspecto presente na obstetrícia enquanto fator de risco de doenças. Para a especialidade genética, a idade materna não é um fator central de risco reprodutivo. A pesquisa constatou que a classificação de uma idade materna ideal para gestar é relativa e suscetível a alterações, segundo o contexto sócio-histórico de cada sociedade.

Abstract Scientific innovations around the study of human chromosomes, which emerged after the mid 20th century, consolidated the incorporation of genetics in prenatal diagnosis. The link between maternal age and genetic syndromes, proposed by biomedical researchers, produced resolutions about risks to pregnant women of a certain age. The article presents biomedicine concepts for advanced maternal age classified as a risk pregnancy. The review of Brazilian and foreign medical manuals in obstetrics and genetics showed different conceptions of risk concerning the reproductive age factor. Maternal age is an aspect in obstetrics related to the risk of diseases. For genetic expertise, advanced maternal age is not a central factor of risk for reproduction. The research found that the classification of an ideal maternal age for pregnancy is relative and susceptible to changes according to the socio-historical context of each society.

miRNAs in decidual NK cells: regulators worthy of attention during pregnancy.

The critical immune effectors, including T, B, and natural killer (NK) cells, dendritic cells, and macrophages participate in regulating immune responses during pregnancy. Among these immune cells, decidual NK (dNK) cells are involved in key placental development processes at the maternal-fetal interface, such as uterine spiral artery remodeling, trophoblast invasion, and decidualization. Mechanistically, dNK cells significantly influence pregnancy outcome by secreting cytokines, chemokines, and angiogenic mediators and by their interactions with trophoblasts and other decidual cells. MicroRNAs (miRNAs) are small non-coding RNA molecules that participate in the initiation and progression of human diseases. Although the functions of circulating miRNAs in pathological mechanism has been extensively studied, the regulatory roles of miRNAs in NK cells, especially in dNK cells, have been rarely reported. In this review, we analyze the effects of miRNA regulations of dNK cell functions on the immune system during gestation. We discuss aberrant expressions of certain miRNAs in dNK cells that may lead to pathological consequences, such as recurrent pregnancy loss (RPL). Interestingly, miRNA expression patterns are also different between dNK cells and peripheral NK (pNK) cells, and pNK cells in the first- and third-trimester of gestation. The dysregulation of miRNA plays a pivotal regulatory role in driving immune functions of dNK and pNK cells. Further understanding of the molecular mechanisms of miRNAs in dNK cells may provide new insights into the development of therapeutics to prevent pregnancy failure.

Evolutionary transcriptomics implicates new genes and pathways in human pregnancy and adverse pregnancy outcomes.

Evolutionary changes in the anatomy and physiology of the female reproductive system underlie the origins and diversification of pregnancy in Eutherian ('placental') mammals. This developmental and evolutionary history constrains normal physiological functions and biases the ways in which dysfunction contributes to reproductive trait diseases and adverse pregnancy outcomes. Here, we show that gene expression changes in the human endometrium during pregnancy are associated with the evolution of human-specific traits and pathologies of pregnancy. We found that hundreds of genes gained or lost endometrial expression in the human lineage. Among these are genes that may contribute to human-specific maternal-fetal communication (HTR2B) and maternal-fetal immunotolerance (PDCD1LG2) systems, as well as vascular remodeling and deep placental invasion (CORIN). These data suggest that explicit evolutionary studies of anatomical systems complement traditional methods for characterizing the genetic architecture of disease. We also anticipate our results will advance the emerging synthesis of evolution and medicine ('evolutionary medicine') and be a starting point for more sophisticated studies of the maternal-fetal interface. Furthermore, the gene expression changes we identified may contribute to the development of diagnostics and interventions for adverse pregnancy outcomes.

Pregnancy is a complicated process. It has three phases: the body recognizes the embryo, it maintains the pregnancy, and finally, it induces labor. These stages happen in all mammals, but the details are different in humans. Human pregnancy and labor last longer. We menstruate. Our placentas invade deeper into the uterus, and the cues that signal pregnancy is done and induce labor are different than in most other mammals. We are also more likely to have pregnancy complications, including infertility, a dangerous rise in blood pressure called preeclampsia, and premature birth. The reasons for these differences are unknown. Human pregnancy relies on close communication between the placenta and the uterus. The immune system must allow the placenta to grow large enough to support the developing embryo, and blood vessels need to adapt to supply gases and nutrients and to remove waste. Understanding how the genes used by the human uterus are different to those used in other species could help explain why human pregnancies are so unusual. Mika, Marinic et al. compared the genes used by the pregnant human uterus to those used in 32 other species, including monkeys, marsupials and other mammals, birds, and reptiles. The analysis revealed that the humans use almost a thousand genes that other animals do not. These genes have roles in the invasion of the placenta, the growth of blood vessels, and control of the immune system. Several have links to the hormone serotonin, which had not been connected with the uterus before. Mika, Marinic et al. suggest that it might control the length of pregnancy, the timing of labor, and communication between parent and baby. The genes identified here provide a starting point for further investigation of human pregnancy. In the future, this may help to prevent or treat infertility, preeclampsia, or premature birth. A possible next step is to examine our closest living relatives, the great apes. Performing similar experiments using tissues or cells from chimpanzees, gorillas, and orangutans could reveal more about the genes unique to human pregnancy.

Cohort profile: Epigenetics in Pregnancy (EPIPREG) - population-based sample of European and South Asian pregnant women with epigenome-wide DNA methylation (850k) in peripheral blood leukocytes.

Pregnancy is a valuable model to study the association between DNA methylation and several cardiometabolic traits, due to its direct potential to influence mother's and child's health. Epigenetics in Pregnancy (EPIPREG) is a population-based sample with the aim to study associations between DNA-methylation in pregnancy and cardiometabolic traits in South Asian and European pregnant women and their offspring. This cohort profile paper aims to present our sample with genetic and epigenetic data and invite researchers with similar cohorts to collaborative projects, such as replication of ours or their results and meta-analysis. In EPIPREG we have quantified epigenome-wide DNA methylation in maternal peripheral blood leukocytes in gestational week 28±1 in Europeans (n = 312) and South Asians (n = 168) that participated in the population-based cohort STORK Groruddalen, in Norway. DNA methylation was measured with Infinium MethylationEPIC BeadChip (850k sites), with technical validation of four CpG sites using bisulphite pyrosequencing in a subset (n = 30). The sample is well characterized with few missing data on e.g. genotype, universal screening for gestational diabetes, objectively measured physical activity, bioelectrical impedance, anthropometrics, biochemical measurements, and a biobank with maternal serum and plasma, urine, placenta tissue. In the offspring, we have repeated ultrasounds during pregnancy, cord blood, and anthropometrics up to 4 years of age. We have quantified DNA methylation in peripheral blood leukocytes in nearly all eligible women from the STORK Groruddalen study, to minimize the risk of selection bias. Genetic principal components distinctly separated Europeans and South Asian women, which fully corresponded with the self-reported ethnicity. Technical validation of 4 CpG sites from the methylation bead chip showed good agreement with bisulfite pyrosequencing. We plan to study associations between DNA methylation and cardiometabolic traits and outcomes.

Loop-mediated isothermal amplification (LAMP) and machine learning application for early pregnancy detection using bovine vaginal mucosal membrane.

An early and accurate pregnancy diagnosis method is required to improve the reproductive performance of cows. Here we developed an easy pregnancy detection method using vaginal mucosal membrane (VMM) with application of Reverse Transcription-Loop-mediated Isothermal Amplification (RT-LAMP) and machine learning. Cows underwent artificial insemination (AI) on day 0, followed by VMM-collection on day 17-18, and pregnancy diagnosis by ultrasonography on day 30. By RNA sequencing of VMM samples, three candidate genes for pregnancy markers (ISG15 and IFIT1: up-regulated, MUC16: down-regulated) were selected. Using these genes, we performed RT-LAMP and calculated the rise-up time (RUT), the first-time absorbance exceeded 0.05 in the reaction. We next determined the cutoff value and calculated accuracy, sensitivity, specificity, positive prediction value (PPV), and negative prediction value (NPV) for each marker evaluation. The IFIT1 scored the best performance at 92.5% sensitivity, but specificity was 77.5%, suggesting that it is difficult to eliminate false positives. We then developed a machine learning model trained with RUT of each marker combination to predict pregnancy. The model created with the RUT of IFIT1 and MUC16 combination showed high specificity (86.7%) and sensitivity (93.3%), which were higher compared to IFIT1 alone. In conclusion, using VMM with RT-LAMP and machine learning algorithm can be used for early pregnancy detection before the return of first estrus.

MINI REVIEW: Role of Kisspeptin-GPR54 system in regulation of reproductive functions in human and other mammals.

Kisspeptin is a 54- amino acid peptide that acts as a ligand of a receptor called GPR54 which is basically a transmembrane receptor that spins seven times across the cell membrane and coupled with G-protein. Kisspeptin regulates the development of reproductive functions and the onset of puberty in human and other mammals by acting at the brain, hypothalamus, pituitary and gonad levels of reproductive axis. Kisspeptin is also involved in regulation of trophoblastic invasion during pregnancy, ovulation, and sperm hyperactivation. Inactivating mutations in human kisspeptin gene (KISS1) cause idiopathic hypogonadotropic hypogonadism. Some mutations in human kisspeptin receptor gene (KISS1R) make the receptor inactive which result in idiopathic hypogonadotropic hypogonadism. Some mutations in human KISS1R gene make the receptor prematurely activated and result in the development of central precocious puberty. Central precocious puberty is also caused by some mutations in human KISS1 gene that make the kisspeptin resistant to degradation. This leads to an increased basal kisspeptin level and subsequently the development of central precocious puberty. Higher kisspeptin level has been detected in the serum and plasma of central precocious puberty patients, which suggest that serum or plasma kisspeptin level can be used as a marker for diagnosis of central precocious puberty.

Analysis of Transcripts of Uncertain Coding Potential Using RNA Sequencing During the Preattachment Phase in Goat Endometrium.

Transcripts of uncertain coding potential (TUCP) are part of long noncoding RNAs, which include short open reading frames and could be translated into small peptides. In recent years, a growing number of TUCPs has been implicated in multiple biological activities, such as embryogenesis and transcriptional regulation. However, the abundance of TUCPs and their roles in goat endometrium during pregnancy recognition (day 16) remain undocumented. In this study, bioinformatics analyses were conducted to identify the differentially expressed (DE) TUCPs between pregnant animals and corresponding nonpregnant controls. A total of 5551 TUCPs were identified; 114 TUCPs were DE in goat endometrium, of which 74 TUCPs were upregulated in pregnant endometrium, whereas 40 TUCPs were downregulated. The related genes of TUCP were predicted by using coexpression and colocalization methods. In summary, 419 genes were predicted by colocalization, and 9464 genes were predicted by coexpression. The kyoto encyclopedia of genes and genomes (KEGG) and gene ontology (GO) analysis showed that TUCPs, which are highly expressed in pregnant endometrium, were mainly associated with endometrial remodeling, nutrient synthesis, and transportation. However, TUCPs that were lowly expressed in pregnant endometrium were mainly associated with immune tolerance, which is necessary for the protection and development of the embryo in the uterus. These findings may be used for the comparative analysis of TUCP transcripts in endometrium and assist in the selection of applicable candidate genes associated with embryo implantation for further functional analyses.

Extracellular vesicle-enriched miRNA profiles across pregnancy in the MADRES cohort.

MicroRNA (miRNA) circulating in plasma have been proposed as biomarkers for a variety of conditions and diseases, including complications during pregnancy. During pregnancy, about 15-25% of maternal plasma exosomes, a small size-class of EVs, are hypothesized to originate in the placenta, and may play a role in communication between the fetus and mother. However, few studies have addressed changes in miRNA over the course of pregnancy with repeated measures, nor focused on diverse populations. We describe changes in miRNA in early and late pregnancy from the MADRES cohort of primarily low-income Hispanic women based in Los Angeles, CA. miRNA derived from extracellular-vesicles (EVs) were isolated from maternal blood plasma samples collected in early and late pregnancy. In this study, we identified 64 of 130 detectable miRNA which significantly increased with gestational age at the time of collection (GA), and 26 which decreased with GA. Possible fetal sex-specific associations were observed for 30 of these 90 significant miRNA. Predicted gene targets for miRNA significantly associated with GA were identified using MirDIP and were found to be enriched for Gene Ontology categories that included energetic and metabolic processes but were underrepresented in immune-related categories. Circulating EV-associated miRNA during pregnancy are likely important for maternal-fetal communication, and may play roles in supporting and maintaining a healthy pregnancy, given the changing needs of the fetus.

Cytokines and pregnancy: Potential regulation by histone deacetylases.

Cytokines are important regulators of pregnancy and parturition. Aberrant expression of proinflammatory cytokines during pregnancy contributes towards preterm labor, pre-eclampsia, and gestational diabetes mellitus. The regulation of cytokine expression in human cells is highly complex, involving interactions between environment, transcription factors, and feedback mechanisms. Recent developments in epigenetic research have made tremendous advancements in exploring histone modifications as a key epigenetic regulator of cytokine expression and the effect of their signaling molecules on various organ systems in the human body. Histone acetylation and subsequent deacetylation by histone deacetylases (HDACs) are major epigenetic regulators of protein expression in the human body. The expression of various proinflammatory cytokines, their role in normal and abnormal pregnancy, and their epigenetic regulation via HDACs will be discussed in this review.

Neutrophils recognize and amplify IFNT signals derived from day 7 bovine embryo for stimulation of ISGs expression in vitro: A possible implication for the early maternal recognition of pregnancy.

Previously, we reported that the presence of multiple day 7 (D7) bovine embryos in the uterus induces systemic immune responses in circulating polymorphonuclear neutrophils (PMNs), but with unknown mechanism. Thus, this study aimed to investigate the direct impact of D7 bovine embryo on PMNs' immune responses in vitro and whether these PMNs can amplify and transfer embryo signals further to another PMN population. PMNs were directly stimulated by embryo culture media (ECM) or interferon tau (IFNT) (10 ng/ml) followed by evaluating mRNA expression by real-time PCR and phenotypic analysis by flow cytometry. To test whether PMNs can transfer embryo signals to a new PMN population, PMNs triggered by ECM or IFNT, were thoroughly washed and diluted to remove any media components, and again were incubated in fresh culture media for 3 h, from which culture supernatants were collected and used as PMN conditioned media (CM) to stimulate a new PMN population. Similar to ECM, IFNT directly stimulated expressions of IFNs (IFNA, IFNG), interferon-stimulated genes (ISGs; OAS1, ISG15, MX1), STAT1, TGFB and IL8, and downregulated TNFA in PMNs. Flow cytometrical analyses demonstrated that IFNT stimulated expressions of pregnancy-related phenotypic markers, CD16 and arginase-1 (ARG1), in PMNs. Most importantly, PMN CM induced ISGs and STAT1 mRNA in fresh PMNs. Since IFNT directly upregulated IFNA expression in PMNs, the impact of IFNA on PMNs' immune responses was further tested. Stimulation of PMNs with IFNA, especially at a low level (1 pg/ml), induced IFNT-like immune responses comparable to those induced by PMN CM. Together, these findings indicated that D7 bovine embryos induce direct anti-inflammatory responses with upregulation of ISGs expressions in PMNs mainly via IFNT. Additionally, PMNs can amplify and transfer embryo signals to a new PMN population in a cell-to-cell communication mechanism possibly mediated in part by IFNA. Such a novel immunological crosstalk might contribute to embryo tolerance and pregnancy establishment in cattle.

Effects of arginase genetic polymorphisms on nitric oxide formation in healthy pregnancy and in preeclampsia.

BACKGROUND AND AIMS: Preeclampsia is associated with reduced nitric oxide (NO) bioavailability. Arginase is related to NO synthesis, but relatively unexplored in preeclampsia. However, no previous study has examined whether variations in ARG1 and ARG2 genes affect NO bioavailability and the risk of preeclampsia. Here, we compared the alleles and genotypes of single nucleotide polymorphisms (SNPs) in ARG1 (rs2781659; rs2781667; rs2246012; rs17599586) and ARG2 (rs3742879; rs10483801) in healthy pregnant women and preeclampsia, and examined whether these SNPs affect plasma nitrite concentrations (a marker of NO formation) in these groups. METHODS: Genotypes for the ARG1 and ARG2 SNPs were determined by Taqman probe and plasma nitrite by an ozone-based chemiluminescence assay. RESULTS: Regarding ARG1 SNPs, the GG genotype and G allele frequencies for rs2781659, and the C allele frequencies for rs2246012 were higher in preeclampsia compared to healthy pregnant women. Moreover, the GG genotype for rs2781659 and the TT genotype for rs2781667 were associated with higher plasma nitrite in healthy pregnant. We found no association of ARG2 polymorphisms with preeclampsia or nitrite levels in the study groups. CONCLUSIONS: Our results suggest that SNPs of ARG1 increase the risk of preeclampsia and modulate plasma nitrite levels in healthy pregnant women.

Association of vitamin D pathway gene polymorphisms with vitamin D level during pregnancy was modified by season and vitamin D supplement.

BACKGROUND & AIMS: This study aims to explore the associations of vitamin D (VD) metabolic pathway gene with 25(OH)D level in pregnant women and the interactions of SNP with season and VD supplement. METHODS: A total of 2658 pregnant women were selected from Zhoushan Pregnant Women Cohort study. Gestational 25(OH)D level and single nucleotide polymorphism (SNP) of VD metabolic pathway gene were detected. Multilinear regression models were used to estimate associations of SNPs with gestational 25(OH)D levels. Stratified analyses were performed to test the interactions of SNP with season and VD supplements. RESULTS: The mutations of rs2298849 and rs7041 on the GC gene were respectively associated with higher 25(OH)D in the first and third trimester; the mutations of seven SNPs (rs1155563, rs16846876, rs17467825, rs2282679, rs2298850, rs3755967, and rs4588) on the GC gene were respectively associated with lower 25(OH)D both in the first and third trimester, and lower changes in 25(OH)D during late pregnancy. The mutations of above seven SNPs, except for rs1155563, were also respectively associated with lower 25(OH)D in the second trimester, but to a lesser extent; Besides, pregnant women with mutation on CYP24A1-rs2209314 had a higher increment in 25(OH)D than their counterparts in the second trimester. The increasing dose effect of Gc isoform on 25(OH)D was observed. The associations of GC and LRP2 genes with 25(OH)D modified by season and VD supplements. CONCLUSIONS: The polymorphisms of VD metabolic pathway gene were associated with gestational 25(OH)D, and the associations differ by seasons and VD supplements. Gc isoform exerted a profound influence on gestational 25(OH)D.

Gestational high fat diet protects 3xTg offspring from memory impairments, synaptic dysfunction, and brain pathology.

Maternal history for sporadic Alzheimer's disease (AD) predisposes the offspring to the disease later in life. However, the mechanisms behind this phenomenon are still unknown. Lifestyle and nutrition can directly modulate susceptibility to AD. Herein we investigated whether gestational high fat diet influences the offspring susceptibility to AD later in life. Triple transgenic dams were administered high fat diet or regular chow throughout 3 weeks gestation. Offspring were fed regular chow throughout their life and tested for spatial learning and memory, brain amyloidosis, tau pathology, and synaptic function. Gestational high fat diet attenuated memory decline, synaptic dysfunction, amyloid-ß and tau neuropathology in the offspring by transcriptional regulation of BACE-1, CDK5, and tau gene expression via the upregulation of FOXP2 repressor. Gestational high fat diet protects offspring against the development of the AD phenotype. In utero dietary intervention could be implemented as preventative strategy against AD.

Factors affecting calving ease in Egyptian buffalo.

Calving ease (CE) is a trait of economic importance that affects animal welfare and farm profitability. The objective of present study was to investigate genetic and environmental factors affecting CE among Primiparous (PP) and multiparous (MP) buffaloes. A total of 9,627 records from 1999 MP and 2,110 PP recorded during the period from 1988 to 2018 were considered. Herd, season of calving, year of calving, birth weight, parity order and gestation length significantly affected CE rate, while age at first calving and sex of calf had no significant effects. Direct and maternal heritabilities of CE in PP and MP were 0.06 and 0.01, respectively. The low heritability of CE indicated that direct selection may not be an effective method to improve CE trait in Egyptian buffalo.

Synergistic action of estradiol and PGE2 on endometrial transcriptome in vivo resembles pregnancy effects better than estradiol alone†.

Successful pregnancy establishment in mammals depends on numerous interactions between embryos and the maternal organism. Estradiol-17ß (E2) is the primary embryonic signal in the pig, and its importance has been questioned recently. However, E2 is not the only molecule of embryonic origin. In pigs, prostaglandin E2 (PGE2) is abundantly synthesized and secreted by conceptuses and endometrium. The present study aimed to determine the role of PGE2 and its simultaneous action with E2 in changes in porcine endometrial transcriptome during pregnancy establishment. The effects of PGE2 and PGE2 acting with E2 were studied using an in vivo model of intrauterine hormone infusions, and were compared to the effects of E2 alone and conceptuses' presence on day 12 of pregnancy. The endometrial transcriptome was profiled using gene expression microarrays followed by statistical analyses. Downstream analyses were performed using bioinformatics tools. Differential expression of selected genes was verified by quantitative polymerase chain reaction. Microarray analysis revealed 2413 differentially expressed genes (DEGs) in the endometrium treated simultaneously with PGE2 and E2 (P < 0.01). No significant effect of PGE2 administered alone on endometrial transcriptome was detected. Gene ontology annotations enriched for DEGs were related to multiple processes such as: focal adhesion, vascularization, cell migration and proliferation, glucose metabolism, tissue remodeling, and activation of immune response. Simultaneous administration of E2 and PGE2 induced more changes within endometrial transcriptome characteristic to pregnancy than infusion of E2 alone. The present findings suggest that synergistic action of estradiol-17ß and PGE2 resembles the effects of pregnancy on endometrial transcriptome better than E2 alone.