Several parameters are important when choosing the most appropriate animal to model human obstetrics, including gestation period, number of fetuses per gestation and placental structure. The domesticated long-tailed chinchilla (Chinchilla lanigera) is a well-suited and appropriate animal model of pregnancy that often will carry only one offspring and has a long gestation period of 105-115 days. Furthermore, the chinchilla placenta is of the haemomonochorial labyrinthine type and is therefore comparable to the human villous haemomonochorial placenta. This proof-of-concept study demonstrated the feasibility in laboratory settings, and demonstrated the potential of the pregnant chinchilla as an animal model for obstetric research and its potential usefulness for non-invasive measurements in the placenta. We demonstrate measurements of the placental and fetal metabolism (demonstrated in vivo by hyperpolarized MRI and in vitro by qPCR analyses), placental vessels (demonstrated ex vivo by contrast-enhanced CT angiography) and overall anatomy (demonstrated in vivo by whole-body CT).

Listeria monocytogenes (LM), a foodborne pathogen, can cause pregnancy failure in animals, especially in ruminants. Recent studies have shown that LM activates inflammasomes to induce IL-1β release in macrophages, however, whether the inflammasome activation regulates LM-induced pregnancy failure remains largely unknown. Here we used mouse model to investigate the molecular mechanism by which LM-induced inflammsome activation contributes to LM-associated pregnancy failure

In utero Zika virus (ZIKV; family Flaviviridae) infection causes a distinct pattern of birth defects and disabilities in the developing fetus and neonate that has been termed congenital zika syndrome (CZS). Over 8,000 children were affected by the 2016 to 2017 ZIKV outbreak in the Americas, many of whom developed CZS as a result of in utero exposure. To date, there is no consensus about how ZIKV causes CZS; animal models, however, are providing mechanistic insights. Using nonhuman primates, immunocompromised mice, immunocompetent mice, and other animal models (e.g., pigs, sheep, guinea pigs, and hamsters), studies are showing that maternal immunological responses, placental infection and inflammation, as well as viral genetic factors play significant roles in predicting the downstream consequences of in utero ZIKV infection on the development of CZS in offspring. There are thousands of children suffering from adverse consequences of CZS. Therefore, the animal models developed to study ZIKV-induced adverse outcomes in offspring could provide mechanistic insights into how other viruses, including influenza and hepatitis C viruses, impact placental viability and fetal growth to cause long-term adverse outcomes in an effort to identify therapeutic treatments.

Obesity before and during pregnancy leads to reduced offspring cardiometabolic health. Here, we systematically reviewed animal experimental evidence of maternal obesity before and during pregnancy and offspring anthropometry and cardiometabolic health. We systematically searched Embase and Medline from inception until January 2018. Eligible publications compared offspring of mothers with obesity to mothers with a normal weight. We performed meta-analyses and subgroup analyses. We also examined methodological quality and publication bias. We screened 2543 publications and included 145 publications (N = 21 048 animals, five species). Essential methodological details were not reported in the majority of studies. We found evidence of publication bias for birth weight. Offspring of mothers with obesity had higher body weight (standardized mean difference (SMD) 0.76 [95% CI 0.60;0.93]), fat percentage (0.99 [0.64;1.35]), systolic blood pressure (1.33 [0.75;1.91]), triglycerides (0.64 [0.42;0.86], total cholesterol (0.46 [0.18;0.73]), glucose level (0.43 [0.24;0.63]), and insulin level (0.81 [0.61;1.02]) than offspring of control mothers, but similar birth weight. Sex, age, or species did not influence the effect of maternal obesity on offspring's cardiometabolic health. Obesity before and during pregnancy reduces offspring cardiometabolic health in animals. Future intervention studies should investigate whether reducing obesity prior to conception could prevent these detrimental programming effects and improve cardiometabolic health of future generations.

Resveratrol (RSV) has been reported to have potential beneficial effects in the complicated pregnancy. Various pregnancy complications lead to a suboptimal in utero environment that impacts fetal growth during critical windows of development. Detrimental structural changes to key organ systems in utero persist into adult life and predispose offspring to an increased risk of chronic non-communicable metabolic diseases such as cardiovascular disease, diabetes and obesity. The aim of this systematic review was to determine the effect of gestational RSV exposure on both maternal and fetal outcomes. Publicly available databases (n = 8) were searched for original studies reporting maternal and/or fetal outcomes after RSV exposure during pregnancy irrespective of species. Of the 115 studies screened, 31 studies were included in this review. RSV exposure occurred for different durations across a range of species (Rats n = 18, Mice n = 7, Japanese Macaques n = 3 and Sheep n = 3), models of complicated pregnancy (eg. maternal dietary manipulations, gestational diabetes, maternal hypoxia, teratogen exposure, etc.), dosages and administration routes. Maternal and fetal outcomes differed not only based on the model of complicated pregnancy assessed but also as a result of species. Given the heterogenic nature of these studies, further investigation assessing RSV exposure during the complicated pregnancy is warranted. In order to make an informed decision regarding the use of RSV to intervene in pregnancy complications, we suggest a minimum data set for consideration in future studies.

The immune health of a farm animal can have significant impact on its overall health, welfare and productivity. One of the most vulnerable physiological states for both humans and animals is pregnancy. Many systemic changes correlate with the gravid state, including shifts in the immune system that may impact the ability to respond optimally to pathogen challenge. Because of this, it would be beneficial to be able to monitor the immune health of the pregnant animals closely. Recently, we developed a new nanoparticle-enabled rapid blood test that can detect ongoing immune responses from both laboratory and farm animals. Here, we report that this novel test reveals highly repeatable and acute changes associated with pregnancy and peri-parturition period in laboratory mice and in cattle. We hypothesize that the test score change reflects changes in the immune status of the gravid females related to the humoral immune response. The test is easy to conduct, of low cost, with results obtained in less than 20 min. This rapid test could be potentially used as an onsite test in local farms and small clinics for animal health management.

Given the significant physiological changes that take place during and resulting from pregnancy, as well as the relative absence of such information in relation to pregnancy termination, this study investigated the potential for developing a valid animal model to objectively assess the biological, physiological and behavioral consequences of drug-induced pregnancy termination. Female Long-Evans rats were divided into four groups (n = 19-21/group), controlling for drug [mifepristone (50 mg/kg/3 ml, i.g.)/misoprostol (0.3 mg/kg/ml, i.g.) or vehicle (1% Carboxymethylcellulose Sodium/0.2% Tween® 80 suspension, i.g.)] and pregnancy. Drug administration took place on days 12-14 of gestation (days 28-40 human gestational equivalent). Vehicle was administered to the controls on the same days. Parameters measured included rat body weight, food intake, vaginal impedance, sucrose consumption/preference, locomotor activity, forced swim test, and home-cage activity. At the termination of the study, rats were deeply anesthetized using urethane, and blood, brain, and liver were collected for biochemical analysis. Following drug/vehicle administration, only the pregnancy termination group (pregnant, drug) displayed a significant decrease in body weight, food intake, locomotor activity-related behaviors and home-cage activity relative to the control group (non-pregnant, vehicle). Additionally, the pregnancy termination group was the only group that displayed a significant reduction in sucrose consumption/preference during Treatment Week relative to Pre-Treatment Week. Vaginal impedance did not significantly decrease over time in parous rats in contrast to all other groups, including the rats in the pregnancy termination group. Biochemical analysis indicated putative drug- and pregnancy-specific influences on oxidative balance. Regression analysis indicated that pregnancy termination was a predictor variable for body weight, food intake and all locomotor activity parameters measured. Moreover, pertaining to body weight and food intake, the pregnancy termination group displayed significant changes, which were not present in a group of naturally miscarrying rats following pregnancy loss. Overall, our results appear to suggest negative biological and behavioral effects following pregnancy termination, that appear to also be distinct from natural miscarriage, and potential benefits of parity pertaining to fecundity. Thus, our findings indicate the importance for further objective investigation of the physiological and behavioral consequences of medical abortion, in order to provide further insight into the potential implications in humans.

Despite the success of postexposure prophylaxis (PEP) of the newborn in preventing mother-to-child transmission of hepatitis B virus), in non-US clinical trials, administering hepatitis B immune globulin (HBIG) to mothers at the end of pregnancy (in addition to passive-active PEP of the newborn) only partially improved outcomes. That is, a significant percentage of newborns became infected during their first year of life. We used a relevant animal model for human IgG transplacental transfer to study dose, time and subclass dependence of HBV neutralizing antibody (nAb) maternal, and fetal levels at the end of pregnancy. Pregnant guinea pigs received 50 or 100 IU/kg HBIGIV 2-5 days before delivery. Human total IgG, IgG subclasses, and nAb in mothers and their litters were measured. In vitro analyses of guinea pig Fc neonatal receptor binding to HBIGIV, as well as to all human IgG subclasses, were also performed. Our study showed that nAb transferred transplacentally from the pregnant guinea pigs to their litters; no transfer occurred during parturition. The amount of the transferred nAb was dose and time dependent. Thus, selection of an efficacious dose in the clinic is important: microdosing may be underdosing, particularly in cases of high viraemia.

The changes in bone homeostasis observed during pregnancy and lactation could result in alterations in the rate of orthodontic tooth movement, but research in human subjects presents significant ethical and practical limitations. Our aim was to compare the amount of orthodontic tooth movement between pregnant/lactating or not animals.

Low food availability leading to reductions in Body Condition Score (BCS; 0 indicates emaciation and 5 obesity) in sheep often coincides with low temperatures associated with the onset of winter in New Zealand. The ability to adapt to reductions in environmental temperature may be impaired in animals with low BCS, in particular during pregnancy when metabolic demand is higher. Here we assess whether BCS affects a pregnant animal's ability to cope with cold challenges.

In-utero nutrition is an under-studied aspect of cognitive development. Fruit has been an important dietary constituent for early hominins and humans. Among 808 eligible CHILD-Edmonton sub-cohort subjects, 688 (85%) had 1-year cognitive outcome data. We found that each maternal daily serving of fruit (sum of fruit plus 100% fruit juice) consumed during pregnancy was associated with a 2.38 point increase in 1-year cognitive development (95% CI 0.39, 4.37; p<0.05). Consistent with this, we found 30% higher learning Performance index (PI) scores in Drosophila offspring from parents who consumed 30% fruit juice supplementation prenatally (PI: 85.7; SE 1.8; p<0.05) compared to the offspring of standard diet parents (PI: 65.0 SE 3.4). Using the Drosophila model, we also show that the cyclic adenylate monophosphate (cAMP) pathway may be a major regulator of this effect, as prenatal fruit associated cognitive enhancement was blocked in Drosophila rutabaga mutants with reduced Ca(2+)-Calmodulin-dependent adenylyl cyclase. Moreover, gestation is a critical time for this effect as postnatal fruit intake did not enhance cognitive performance in either humans or Drosophila. Our study supports increased fruit consumption during pregnancy with significant increases in infant cognitive performance. Validation in Drosophila helps control for potential participant bias or unmeasured confounders.

Ultrasound is a noninvasive routine method that allows real-time monitoring of fetal development in utero to determine gestational age and to detect congenital anomalies and multiple pregnancies. To date, the developmental biology of Chinchilla lanigera has not yet been characterized. This species has been found to undergo placentation, long gestation, and fetal dimensions similar to those in humans. The aim of this study was to assess the use of high-frequency ultrasound (HFUS) and clinical ultrasound (US) to predict gestational age in chinchillas and evaluate the possibility of this species as a new animal model for the study of human pregnancy. In this study, 35 pregnant females and a total of 74 embryos and fetuses were monitored. Ultrasound examination was feasible in almost all chinchilla subjects. It was possible to monitor the chinchilla embryo with HFUS from embryonic day (E) 15 to 60 and with US from E15 to E115 due to fetus dimensions. The placenta could be visualized and measured with HFUS from E15, but not with US until E30. From E30, the heartbeat became detectable and it was possible to measure fetal biometrics. In the late stages of pregnancy, stomach, eyes, and lenses became visible. Our study demonstrated the importance of employing both techniques while monitoring embryonic and fetal development to obtain an overall and detailed view of all structures and to recognize any malformation at an early stage. Pregnancy in chinchillas can be confirmed as early as the 15th day postmating, and sonographic changes and gestational age are well correlated. The quantitative measurements of fetal and placental growth performed in this study could be useful in setting up a database for comparison with human fetal ultrasounds. We speculate that, in the future, the chinchilla could be used as an animal model for the study of US in human pregnancy.

Deficiency of folate, an essential vitamin for DNA synthesis and methylation, is reported as a risk factor for mental disorders. Considering a possibility that folate metabolism deficit during pregnancy may disturb CNS development and increase mental disorders in offspring, we treated pregnant rats with methotrexate (MTX), an inhibitor of folate metabolic enzyme, and evaluated offspring behaviors.

Many important molecular events associated with implantation and development occur within the female reproductive tract, especially within the uterus endometrium, during pregnancy periods. The endometrium includes the mucosal lining of the uterus, which provides a suitable site for implantation and development of a fertilized egg and fetus. To date, the molecular cascades in the uterus endometrium during pregnancy periods in pigs have not been elucidated fully. In this study, we compared the functional regulated proteins in the endometrium during pregnancy periods with those in non-pregnant conditions and investigated changes in expression patterns during pregnancy (days 40, 70, and 93) using two-dimensional gel electrophoresis (2-DE) and western blotting. The functional regulated proteins were identified and discovered from differentially expressed proteins in the uterus endometrium during pregnancy. We discovered 820 protein spots in a proteomic analysis of uterus endometrium tissues with 2-DE gels. We identified 63 of the 98 proteins regulated differentially among non-pregnant and pregnant tissues (matched and unmatched spots). Interestingly, 10 of these 63 proteins are development-, cytoskeleton- and chaperon-related proteins such as transferrin, protein DJ-1, transgelin, galectin-1, septin 2, stathmin 1, cofilin 1, fascin 1, heat shock protein (HSP) 90β and HSP 27. The specific expression patterns of these proteins in the endometrium during pregnancy were confirmed by western blotting. Our results suggest that the expressions of these genes involved in endometrium function and endometrium development from early to late gestation are associated with the regulation of endometrium development for maintaining pregnancy.

Pregnancy toxaemia is a metabolic disorder with a high mortality rate and occurs in twin-bearing ewes in late gestation. Maternal hypoglycaemia is a characteristic symptom of the disease and has been attributed to an increase in glucose uptake by the twin-bearing uterus. The possibility that a reduced maternal glucose production rate might cause hypoglycaemia, has received little attention in the past. It was the aim of this study to investigate this explanation as a possible alternative. Six ewes were sequentially subjected to two types of hypoglycaemic stress, firstly by fasting for 14 h and secondly through induction of moderate hyperketonaemia. Glucose kinetics were assessed in each animal during the dry non-gestational period, during late gestation, and during early lactation. Application of these stress factors was associated with variation of plasma glucose concentration from 4.9 to 0.87 mmol L(-1). The plasma glucose concentration was always significantly related to the glucose production rate. The greatest stress-induced reductions in glucose concentration and glucose production rate were seen during late gestation in twin-bearing ewes. The decline in the glucose production rate after an overnight fast and during induced hyperketonaemia was greater in twin-bearing ewes than in single-bearing ewes (59% and 43%, respectively, p<0.05). The stress conditions resulted in the lowest levels of glucose concentration and glucose turnover rates in the stressed, hyperketonaemic, late gestation twin-bearing ewes. This illustrates that the glucose homoeostatic system of ewes bearing twins is significantly more susceptible to hypoglycaemic stress than that of ewes bearing single lambs. These findings also show that the primary cause of hypoglycaemia in late gestation twin-pregnant ewes is an increased susceptibility to a stress related reduction in glucose production rate. This metabolic condition leaves the twin-pregnant ewe predisposed for the development of pregnancy toxaemia.

Tosyl activated magnetic beads were used for aptamer selection against PAG- 7 and 18 proteins of bovine origin. PAG proteins were immobilized on beads with further addition of biotin tagged aptamer library. The recognition of aptamers with PAG was identified by ST-HRP based approach which was colorimetric in nature. The selected aptamers were sequenced and at the same time several new aptamers were identified. Later M-fold structure and G-quadruplex score of aptamers were analyzed for their selection. Those aptamers having high G value and complex structure were chosen. In dot blot assay, aptamers recognized PAG protein in an animal after 42 days of artificial insemination which later given birth to a healthy calf. Further the cross reactivity with serum of 0th day animal (post AI) or with non pregnant animal serum was minimal. Aptamers have also shown interaction with PAG protein of buffalo origin. These selected aptamers have commercial application especially in development of biosensors for early detection of pregnancy in bovine.

Information obtained from peripheral blood could help us understand the underlying mechanisms in autoimmune diseases, cancer, pregnancy, and other conditions. In this paper, we present the protein map of porcine peripheral blood mononuclear cells (PBMC) to better understand the molecular expression changes that occur during pregnancy using proteomic analysis. We detected 94 differentially expressed proteins in pregnant vs. non-pregnant (NP) pigs, and a representative set of the proteins was subjected to LC-MS/MS analysis. Furthermore, the identified proteins were categorized according to their biological process and molecular function. By classifying the proteins according to their functions, a large number of differentially regulated proteins involved in anti-oxidant, detoxification and stress response pathways were found, including peroxiredoxin (PRX) 1, 2, and 6, glutathione-S-transferase (GST), annexin A2, and A6, and heat shock protein 27 (HSP 27) during pregnancy (pregnancy d of E40, embryonic day 40; E70, embryonic day 70; and E93, embryonic day 93) compared with non-pregnancy. In this study, a proteomic approach utilizing 2-DE and LC-MS/MS was applied to evaluate specific molecular expression changes during pregnancy compared with non-pregnancy. Together, these data offer new information about the proteome map and factors that are differentially regulated during maintenance of normal pregnancy.

During pregnancy, maternal metabolism undergoes substantial changes to support the developing fetus. Such changes are finely regulated by different mechanisms carried out by effectors such as microRNAs (miRNAs). These small non-coding RNAs regulate numerous biological functions, mostly through post-transcriptional repression of gene expression. miRNAs are also secreted in circulation by numerous organs, such as the placenta. However, the complete plasmatic microtranscriptome of pregnant women has still not been fully described, although some miRNA clusters from the chromosome 14 (C14MC) and the chromosome 19 (C19MC and miR-371-3 cluster) have been proposed as being specific to pregnancy. Our aims were thus to describe the plasma microtranscriptome during the first trimester of pregnancy, by assessing the differences with non-pregnant women, and how it varies between the 4th and the 16th week of pregnancy.

This paper reviews the findings from preclinical animal and human clinical research investigating maternal/fetal, neonatal, and child neurodevelopmental outcomes following prenatal exposure to psychotropic drugs. Evidence for the risks associated with prenatal exposure was examined, including teratogenicity, neurodevelopmental effects, neonatal toxicity, and long-term neurobehavioral consequences (i.e., behavioral teratogenicity). We conducted a comprehensive review of the recent results and conclusions of original research and reviews, respectively, which have investigated the short- and long-term impact of drugs commonly prescribed to pregnant women for psychological disorders, including mood, anxiety, and sleep disorders. Because mental illness in the mother is not a benign event, and may itself pose significant risks to both mother and child, simply discontinuing or avoiding medication use during pregnancy may not be possible. Therefore, prenatal exposure to psychotropic drugs is a major public health concern. Decisions regarding drug choice, dose, and duration should be made carefully, by balancing severity, chronicity, and co-morbidity of the mental illness, disorder, or condition against the potential risk for adverse outcomes due to drug exposure. Globally, maternal mental health problems are considered as a major public health challenge, which requires a stronger focus on mental health services that will benefit both mother and child. More preclinical and clinical research is needed in order to make well-informed decisions, understanding the risks associated with the use of psychotropic medications during pregnancy.

The purpose of this study was to describe intake procedures in Colorado animal shelters, compare infectious disease screening protocols in shelters taking in animals from out-of-state to shelters only accepting animals from Colorado, and analyze perceived risk of diseases in Colorado by responding shelter personnel. A questionnaire was designed and administered to shelter personnel across the state of Colorado via the survey tool SurveyMonkey© (http://www.surveymonkey.com) or a mailed hard copy. Information collected concerned general shelter characteristics and intake procedures performed in various circumstances as reported by responding shelter personnel. Only 12.5% (5/40) of respondents reported providing core vaccines to all animals upon intake at their shelter, with young age (65.0%; 26/40), pregnancy (55.0%; 22/40), and mild existing illness (40.0%; 16/40) being cited as the top reasons for not administering core vaccines. A significantly larger proportion of shelters taking animals in from around the U.S. screened for Dirofilaria immitis than shelters taking in animals only from within the state of Colorado (p = 0.001), though a majority of respondents considered cats and dogs to be at risk of heartworm and endoparasitic infection in the state of Colorado. Based on the results of this questionnaire, relatively few shelters test dogs and cats for infectious diseases and some of those utilize tests for diagnostic purposes rather than routine screening. Additionally, vaccination protocols in several shelters are not consistent with The Association of Shelter Veterinarians Guidelines for Standards of Care in Animal Shelters. This study provides important information on intake procedures in Colorado animal shelters and highlights the importance of educating shelter staff on varying risk of infection based on the history and origin of the animal being taken in.