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Pathologic Evaluation of Type 2 Porcine Reproductive and Respiratory Syndrome Virus Infection at the Maternal-Fetal Interface of Late Gestation Pregnant Gilts.

ABSTRACT: The pathogenesis of fetal death caused by porcine reproductive and respiratory syndrome virus (PRRSV) remains unclear. The objective of this study was to improve our understanding of the pathogenesis by assessing potential relationships between specific histopathological lesions and PRRSV RNA concentration in the fetuses and the maternal-fetal interface. Pregnant gilts were inoculated with PRRSV (n = 114) or sham inoculated (n = 19) at 85±1 days of gestation. Dams and their litters were humanely euthanized and necropsied 21 days later. PRRSV RNA concentration was measured by qRT-PCR in the maternal-fetal interface and fetal thymus (n = 1391). Presence of fetal lesions was positively related to PRRSV RNA concentration in the maternal-fetal interface and fetal thymus (P<0.05 for both), but not to the distribution or severity of vasculitis, or the severity of endometrial inflammation. The presence of fetal and umbilical lesions was associated with greater odds of meconium staining (P<0.05 for both). The distribution and severity of vasculitis in endometrium were not significantly related to PRRSV RNA concentration in maternal-fetal interface or fetal thymus. Endometrial inflammation severity was positively related to distribution and severity of vasculitis in endometrium (P<0.001 for both). Conclusions from this study suggest that type 2 PRRSV infection in pregnant gilts induces significant histopathological lesions at maternal-fetal interface, but they are not associated with presence of PRRSV in the maternal-fetal interface at 21 days post infection. Conversely, fetal pathological lesions are associated with presence of PRRSV in the maternal-fetal interface and fetal thymus, and meconium staining is significantly associated with the presence of both fetal and umbilical lesions observed 21 days post infection.

SUBMITTER: Novakovic P

PROVIDER: S-EPMC4786155 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Pathologic Evaluation of Type 2 Porcine Reproductive and Respiratory Syndrome Virus Infection at the Maternal-Fetal Interface of Late Gestation Pregnant Gilts.

Novakovic Predrag P Harding John C S JC Al-Dissi Ahmad N AN Ladinig Andrea A Detmer Susan E SE

PloS one 20160310 3

The pathogenesis of fetal death caused by porcine reproductive and respiratory syndrome virus (PRRSV) remains unclear. The objective of this study was to improve our understanding of the pathogenesis by assessing potential relationships between specific histopathological lesions and PRRSV RNA concentration in the fetuses and the maternal-fetal interface. Pregnant gilts were inoculated with PRRSV (n = 114) or sham inoculated (n = 19) at 85±1 days of gestation. Dams and their litters were humanely ...[more]

PMID: 26963101

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Project description:The phenotype and function of immune cells that reside at the maternal-fetal interface in humans and mice have been, and still are, extensively studied with the aim to fully comprehend the complex immunology of pregnancy. In pigs, information regarding immune cell phenotypes is limited and mainly focused on early gestation whereas late gestation has not yet been investigated. We designed a unique methodology tailored to the porcine epitheliochorial placenta, which allowed us to address immune phenotypes separately in the maternal endometrium (ME) and fetal placenta (FP) by flow cytometry. In-depth phenotyping of NK cells, non-conventional and conventional T cells within maternal blood (mBld), ME, FP, and fetal spleen (fSpln) revealed major differences between these anatomic sites. In both maternal compartments, all NK cells were perforin+ and had NKp46-defined phenotypes indicative of late-stage differentiation. Likewise, T cells with a highly differentiated phenotype including CD2+CD8α+CD27dim/-perforin+ γδ T cells, CD27-perforin+ cytolytic T cells (CTLs), and T-bet+ CD4+CD8α+CD27- effector memory T (Tem) cells prevailed within these compartments. The presence of highly differentiated T cells was also reflected in the number of cells that had the capacity to produce IFN-γ. In the FP, we found NK cells and T cell populations with a naive phenotype including CD2+CD8α-CD27+perforin- γδ T cells, T-bet-CD4+CD8α-CD27+ T cells, and CD27+perforin- CTLs. However, also non-naive T cell phenotypes including CD2+CD8α+CD27+perforin- γδ T cells, T-bet+CD4+CD8α+CD27- Tem cells, and a substantial proportion of CD27-perforin+ CTLs resided within this anatomic site. Currently, the origin or the cues that steer the differentiation of these putative effector cells are unclear. In the fSpln, NKp46high NK cells and T cells with a naive phenotype prevailed. This study demonstrated that antigen-experienced immune cell phenotypes reside at the maternal-fetal interface, including the FP. Our methodology and our findings open avenues to study NK and T cell function over the course of gestation. In addition, this study lays a foundation to explore the interplay between immune cells and pathogens affecting swine reproduction.

Project description:Background:Mammary gland development during late gestation in gilts is a major factor that alters the composition of colostrum and growth performance of piglets. Plasma valine is taken up and metabolized extensively by the mammary gland; however, the effects of valine on mammary gland development during late gestation are still unclear. Thirty primiparous gilts were divided into three treatment groups (n =?10) and received one of the three diets starting on day 75 of gestation until the day of farrowing. The total dietary valine to lysine ratio of the three diets was 0.63 (LV), 0.73 (MV), and 0.93 (HV), respectively. Results:Dietary valine supplementation during late gestation did not affect (P >?0.05) the litter size and weight at farrowing; however, the piglet weight and average daily gain at weaning were linearly increased (P <?0.05) as the dietary valine increased. The highest piglet weight at weaning was observed when the gilts were provided the HV diet. Dietary valine supplementation linearly elevated (P <?0.05) protein, fat and solids-not-fat and some free amino acids content in colostrum. The concentration of prolactin in plasma of gilts was linearly increased in response to valine supplementation at days 1 and 10 of lactation (P <?0.05). Furthermore, with increasing dietary valine allowance, a linear increase (P <?0.05) was observed in the area of the lumen of alveolus and the content of DNA, RNA, and total protein in the mammary tissues at day 1 of lactation. Moreover, the protein expression of cyclin D1, p-mTOR, p-S6, and p-4EBP1 was also linearly increased (P <?0.05) in the mammary tissue at day 1 of lactation. However, no difference (P >?0.05) was observed in the indices related to mammary development and the mTOR signaling pathway at day 21 of lactation. Conclusion:The results revealed that increasing the total dietary valine to lysine ratio to 0.93 during late gestation significantly enhances the piglet weight and average daily gain at weaning probably due to improved development of mammary gland.

Project description:BACKGROUND:Previous studies have shown a correlation between fluoride concentrations in urine and community water fluoride concentrations. However, there are no studies of the relationship between community water fluoridation, urine, serum, and amniotic fluid fluoride concentrations in pregnant women in the US. The aim of this study was to determine the relationship between maternal urine fluoride (MUF), maternal urine fluoride adjusted for specific gravity (MUFSG), maternal serum fluoride (MSF), amniotic fluid fluoride (AFF) concentrations during pregnancy, and community water fluoridation in Northern California. METHODS:Archived samples of urine, serum and amniotic fluid collected from second trimester pregnant women in Northern California from 47 different communities in Northern California and one from Montana (n =?48), were analyzed for fluoride using an ion specific electrode following acid microdiffusion. Women's addresses were matched to publicly reported water fluoride concentrations. We examined whether fluoride concentrations in biospecimens differed by fluoridation status of the community water, and determined the association between water fluoride concentrations and biospecimen fluoride concentrations using linear regression models adjusted for maternal age, smoking, Body Mass Index (BMI), race/ethnicity, and gestational age at sample collection. RESULTS:Fluoride concentrations in the community water supplies ranged from 0.02 to 1.00?mg/L. MUF, MSF , and AFF concentrations were significantly higher in pregnant women living in communities adhering to the U.S. recommended water fluoride concentration (0.7?mg/L), as compared with communities with less than 0.7?mg/L fluoride in drinking water. When adjusted for maternal age, smoking status, BMI, race/ethnicity, and gestational age at sample collection, a 0.1?mg/L increase in community water fluoride concentration was positively associated with higher concentrations of MUF (B?=?0.052, 95% CI:0.019,0.085), MUFSG (B = 0.028, 95% CI: -0.006, 0.062), MSF (B?=?0.001, 95% CI: 0.000, 0.003) and AFF (B?=?0.001, 95% CI: 0.000, 0.002). CONCLUSIONS:We found universal exposure to fluoride in pregnant women and to the fetus via the amniotic fluid. Fluoride concentrations in urine, serum, and amniotic fluid from women were positively correlated to public records of community water fluoridation. Community water fluoridation remains a major source of fluoride exposure for pregnant women living in Northern California.

Project description:Background: Prenatal exposure to serotonin reuptake inhibitor (SRI) antidepressants increases risk for adverse neurodevelopmental outcomes, yet little is known about whether effects are present before birth. In relation to maternal SRI pharmacokinetics, this study investigated chronic and acute effects of prenatal SRI exposure on third-trimester fetal heart rate variability (HRV), while evaluating confounding effects of maternal depressed mood. Methods: At 36-weeks' gestation, cardiotocograph measures of fetal HR and HRV were obtained from 148 pregnant women [four groups: SRI-Depressed (n = 31), SRI-Non-Depressed (n = 18), Depressed (unmedicated; n = 42), and Control (n = 57)] before, and ~5-h after, typical SRI dose. Maternal plasma drug concentrations were quantified at baseline (pre-dose) and four time-points post-dose. Mixed effects modeling investigated group differences between baseline/pre-dose and post-dose fetal HR outcomes. Post hoc analyses investigated sex differences and dose-dependent SRI effects. Results: Maternal SRI plasma concentrations were lowest during the baseline/pre-dose fetal assessment (trough) and increased to a peak at the post-dose assessment; concentration-time curves varied widely between individuals. No group differences in fetal HR or HRV were observed at baseline/pre-dose; however, following maternal SRI dose, short-term HRV decreased in both SRI-exposed fetal groups. In the SRI-Depressed group, these post-dose decreases were displayed by male fetuses, but not females. Further, episodes of high HRV decreased post-dose relative to baseline, but only among SRI-Non-Depressed group fetuses. Higher maternal SRI doses also predicted a greater number of fetal HR decelerations. Fetuses exposed to unmedicated maternal depressed mood did not differ from Controls. Conclusions: Prenatal SRI exposure had acute post-dose effects on fetal HRV in late gestation, which differed depending on maternal mood response to SRI pharmacotherapy. Importantly, fetal SRI effects were sex-specific among mothers with persistent depressive symptoms, as only male fetuses displayed acute HRV decreases. At trough (pre-dose), chronic fetal SRI effects were not identified; however, concurrent changes in maternal SRI plasma levels suggest that fetal drug exposure is inconsistent. Acute SRI-related changes in fetal HRV may reflect a pharmacologic mechanism, a transient impairment in autonomic functioning, or an early adaption to altered serotonergic signaling, which may differ between males and females. Replication is needed to determine significance with postnatal development.

Dataset Information

Pathologic Evaluation of Type 2 Porcine Reproductive and Respiratory Syndrome Virus Infection at the Maternal-Fetal Interface of Late Gestation Pregnant Gilts.

Publications

Pathologic Evaluation of Type 2 Porcine Reproductive and Respiratory Syndrome Virus Infection at the Maternal-Fetal Interface of Late Gestation Pregnant Gilts.

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