Litter Survival Research Articles

Chd8 haploinsufficiency impacts rearing experience in C57BL/6 mice.

Mutations in CHD8 are one of the highest genetic risk factors for autism spectrum disorder. Studies in mice that investigate underlying mechanisms have shown Chd8 haploinsufficient mice display some trait disruptions that mimic clinical phenotypes, although inconsistencies have been reported in some traits across different models on the same strain background. One source of variation across studies may be the impact of Chd8 haploinsufficiency on maternal-offspring interactions. While differences in maternal care as a function of Chd8 genotype have not been studied directly, a previous study showed that pup survival was reduced when reared by Chd8 heterozygous dams compared with wild-type (WT) dams, suggesting altered maternal care as a function of Chd8 genotype. Through systematic observation of the C57BL/6 strain, we first determined the impact of Chd8 haploinsufficiency in the offspring on WT maternal care frequencies across preweaning development. We next determined the impact of maternal Chd8 haploinsufficiency on pup care. Compared with litters with all WT offspring, WT dams exhibited less frequent maternal behaviors toward litters consisting of offspring with mixed Chd8 genotypes, particularly during postnatal week 1. Dam Chd8 haploinsufficiency decreased litter survival and increased active maternal care also during postnatal week 1. Determining the impact of Chd8 haploinsufficiency on early life experiences provides an important foundation for interpreting offspring outcomes and determining mechanisms that underlie heterogeneous phenotypes.

The post-emergence period for denning Polar Bears: phenology and influence on cub survival

Abstract Among polar bears (Ursus maritimus), only parturient females den for extended periods, emerging from maternal dens in spring after having substantially depleted their energy reserves during a fast that can exceed 8 months. Although den emergence coincides with a period of increasing prey availability, polar bears typically do not depart immediately to hunt, but instead remain at the den for up to a month. This delay suggests that there are likely adaptive advantages to remaining at the den between emergence and departure, but the influence of the timing and duration of this post-emergence period on cub survival has not been evaluated previously. We used temperature and location data from 70 denning bears collared within the Southern Beaufort Sea and Chukchi Sea subpopulations to estimate the phenology of the post-emergence period. We evaluated the influence of various spatial and temporal features on duration of the post-emergence period and evaluated the potential influence of post-emergence duration on litter survival early in the spring following denning. For dens that likely contained viable cubs at emergence (n = 56), mean den emergence occurred on 16 March (SE = 1.4 days) and mean departure on 24 March (SE = 1.6 days), with dates typically occurring later in the Chukchi Sea relative to Southern Beaufort Sea and on land relative to sea ice. Mean duration of the post-emergence period was 7.9 days (SE = 1.4) for bears that were observed with cubs later in the spring, which was over 4 times longer than duration of those observed without cubs (1.9 days). Litter survival in the spring following denning (n = 31 dens) increased from 0.5 to 0.9 when duration of the post-emergence period increased by ~4 days and other variables were held at mean values. Our limited sample size and inability to verify cub presence at emergence suggests that future research is merited to improve our understanding of this relationship. Nonetheless, our results highlight the importance of the post-emergence period in contributing to reproductive success and can assist managers in developing conservation and mitigation strategies in denning areas, which will be increasingly important as human activities expand in the Arctic.

Asymptomatic viral infection is associated with lower host reproductive output in wild mink populations

Many endemic viruses circulate in populations without hosts showing visible signs of disease, while still having the potential to alter host survival or reproduction. Aleutian Mink Disease Virus (AMDV) circulates in many American mink (Neogale vison) populations in its native and introduced ranges. In this study, we analysed how AMDV infection in female American mink affects the reproduction of a feral population. Females infected with AMDV delivered significantly smaller litters (5.8 pups) than uninfected females (6.3 pups), meaning their litter size was reduced by 8%. Larger females and yearling females had larger litters than smaller and older females. There were no significant differences in whole litter survival between infected and uninfected females; however, offspring survival until September or October within litters of infected females was 14% lower than that within those of uninfected females. This negative link between infection and reproductive output means that Aleutian disease could seriously affect the wild mink population. This study increases our understanding of the threats posed by the spread of viruses to wildlife from farm animals or humans, highlighting that viruses circulating in wildlife, even in the absence of clinical manifestation, can be important drivers of population dynamics in wildlife.

The fetal response to maternal inflammation is dependent upon maternal IL-6 in a murine model

BackgroundThe induction of maternal inflammation in mice leads to fetal injury that is believed to be IL-6 dependent. The fetal inflammatory response, defined by elevated fetal or amniotic fluid IL-6, has been described as a potential mechanism for subsequent fetal injury. The role of maternal IL-6 production and signaling in the fetal IL-6 response is currently unclear. MethodsGenetic and anti-IL-6 antibody strategies were used to systematically block the maternal IL-6 response during inflammation. Chorioamnionitis was induced using intraperitoneal injection of lipopolysaccharide (LPS) at mid gestation (E14.5) and late gestation (E18.5). This model was used in pregnant C57Bl/6 dams, IL6-/- dams, C57Bl/6 dams treated with anti-IL-6 (blocks both classical and trans-signaling) or anti-gp130 antibodies (blocks trans-signaling only) and IL6+/− dams. Six hours following LPS injection, maternal serum, placental tissue, amniotic fluid and fetal tissue or serum were collected. A bead-based multiplex assay was used to evaluate levels of IL-6, KC, IL-1β, TNF, IL-10, IL-22, IFN-γ, IL-13 and IL-17A. ResultsChorioamnionitis in C57Bl/6 dams was characterized by elevated maternal serum levels of IL-6, KC and IL-22 with litter loss during mid gestation. The fetal response to maternal inflammation in C57Bl/6 mice was primarily characterized by elevated levels of IL-6, KC and IL-22 in the placenta, amniotic fluid and fetus during both mid and late gestation. A global IL-6 knockout (IL6-/-) eradicated the maternal, placental, amniotic fluid and fetal IL-6 response to LPS during mid and late gestation and improved litter survival, while minimally influencing the KC or IL-22 responses. Blocking maternal classical IL-6 signaling in C57Bl/6 dams at the time of LPS exposure diminished the maternal, placental, amniotic fluid and fetal IL-6 response during mid and late gestation, while blocking maternal IL-6 trans-signaling only affected fetal IL-6 expression. To evaluate whether maternal IL-6 was crossing the placenta and reaching the fetus, IL-6+/− dams were utilized in the chorioamnionitis model. IL-6+/− dams mounted a systemic inflammatory response following injection with LPS, characterized by elevated IL-6, KC and IL-22. IL-6-/- pups born to IL6+/− dams had decreased amniotic fluid levels of IL-6 and undetectable levels of fetal IL-6 compared to IL-6+/+ littermate controls. ConclusionThe fetal response to systemic maternal inflammation is dependent upon maternal IL-6 signaling, but maternal IL-6 is not crossing the placenta and reaching the fetus at detectable levels.

Reproductive senescence in polar bears in a variable environment

Reproductive senescence is ubiquitous in mammals. However, patterns of senescence vary across reproductive traits, even within populations, perhaps because of differences in selection pressures, physiological constraints, and responses to environmental conditions. We investigated reproductive senescence in wild female polar bears (Ursus maritimus), using 31 years of capture-recapture data from the Svalbard area. We studied the influence of environmental conditions on age-specific litter production and litter size using generalized linear mixed models. Further, using a capture-recapture model that handles the dependency between vital rates of individuals belonging to the same family unit, we assessed maternal-age-related changes in first year cub and litter survival. We provide clear evidence for reproductive senescence in female polar bears. Litter production and litter size peaked in middle-aged females and declined sharply afterward. By contrast cub and litter survival did not decline after prime age. We found no evidence of terminal investment. The reproductive output of all females was affected by sea-ice conditions during the previous year and the Arctic Oscillation, with some effects differing greatly between age groups. Old females were affected the most by environmental conditions. Our results suggest that the decline in reproductive output is a combination of fertility and body-condition senescence, with a weak contribution of maternal-effect senescence, possibly due to benefits of experience. Further, as predicted by evolutionary theory, senescence appears to be a consequence of failures in early stages of the reproductive cycle rather than in late stages, and environmental variation affected old females more than prime-aged females. Our study emphasizes the need to study several reproductive traits and account for environmental variation when investigating reproductive senescence. Differences in senescence patterns across reproductive traits should be interpreted in light of evolutionary theory and while considering underlying physiological drivers.

Impact of breeding for reduced methane emissions in New Zealand sheep on maternal and health traits.

Enteric methane emissions from ruminants account for ∼35% of New Zealand’s greenhouse gas emissions. This poses a significant threat to the pastoral sector. Breeding has been shown to successfully lower methane emissions, and genomic prediction for lowered methane emissions has been introduced at the national level. The long-term genetic impacts of including low methane in ruminant breeding programs, however, are unknown. The success of the New Zealand sheep industry is currently heavily reliant on the prolificacy, fecundity and survival of adult ewes. The objective of this study was to determine genetic and phenotypic correlations between adult maternal ewe traits (live weight, body condition score, number of lambs born, litter survival to weaning, pregnancy scanning and fleece weight), faecal and Nematodirus egg counts and measures of methane in respiration chambers. More than 9,000 records for methane from over 2,200 sheep measured in respiration chambers were collected over 10 years. Sheep were fed on a restricted diet calculated as approximately twice the maintenance. Methane measures were converted to absolute daily emissions of methane measured in g per day (CH4/day). Two measures of methane yield were recorded: the ratio of CH4 to dry matter intake (g CH4/kg DMI; CH4/DMI) and the ratio of CH4 to total gas emissions (CH4/(CH4 + CO2)). Ewes were maintained in the flocks for at least two parities. Non-methane trait data from over 8,000 female relatives were collated to estimate genetic correlations. Results suggest that breeding for low CH4/DMI is unlikely to negatively affect faecal egg counts, adult ewe fertility and litter survival traits, with no evidence for significant genetic correlations. Fleece weight was unfavourably (favourably) correlated with CH4/DMI (rg = −0.21 ± 0.09). Live weight (rg = 0.3 ± 0.1) and body condition score (rg = 0.2 ± 0.1) were positively correlated with methane yield. Comparing the two estimates of methane yield, CH4/DMI had lower heritability and repeatability. However, correlations of both measures with adult ewe traits were similar. This suggests that breeding is a suitable mitigation strategy for lowering methane yield, but wool, live weight and fat deposition traits may be affected over time and should be monitored.

Fascin is essential for mammary gland lactogenesis

Fascin expression has commonly been observed in certain subtypes of breast cancer, where its expression is associated with poor clinical outcome. However, its role in normal mammary gland development has not been elucidated. Here, we used a fascin knockout mouse model to assess its role in normal mammary gland morphogenesis and lactation. Fascin knockout was not embryonically lethal, and its effect on the litter size or condition at birth was minimal. However, litter survival until the weaning stage significantly depended on fascin expression solely in the nursing dams. Accordingly, pups that nursed from fascin−/− dams had smaller milk spots in their abdomen, suggesting a lactation defect in the nursing dams. Mammary gland whole-mounts of pregnant and lactating fascin−/− mice showed significantly reduced side branching and alveologenesis. Despite a typical composition of basal, luminal, and stromal subsets of mammary cells and normal ductal architecture of myoepithelial and luminal layers, the percentage of alveolar progenitors (ALDH+) in fascin−/− epithelial fraction was significantly reduced. Further in-depth analyses of fascin−/− mammary glands showed a significant reduction in the expression of Elf5, the master regulator of alveologenesis, and a decrease in the activity of its downstream target p-STAT5. In agreement, there was a significant reduction in the expression of the milk proteins, whey acidic protein (WAP), and β-casein in fascin−/− mammary glands. Collectively, our data demonstrate, for the first time, the physiological role of fascin in normal mammary gland lactogenesis, an addition that could reveal its contribution to breast cancer initiation and progression.

Effects of farrowing hut design on maternal and thermoregulatory behaviour in outdoor housed sows and piglets

This study aimed to determine the effect of three different farrowing huts on the behaviour of outdoor housed sows and piglets during summer in Eastern Canada, with a focus on thermoregulatory and crushing behaviours. Forty-two second parity sows were housed outdoors in groups of three during lactation (N = 42). Within each group, sows had access to three farrowing huts: a Wood modified A-frame hut, a Plastic round calf hutch, and a Metal ark English-style hut. Cameras were installed in the huts to observe behaviour on days 1, 2, 7 and 14 of lactation. Temperature and humidity were recorded outside and inside the huts. Hourly temperature averages were analysed for the effect of the hut type for day and night separately. Sows farrowed in the huts between August and October and observations of sow and piglet location, posture, nursing, and crushing events were collected in the morning and afternoon. The Wood huts showed the least variation in temperature between days and nights, with the Metal huts showing similar thermal properties to the Wood huts (P < 0.05). The Plastic hut was hotter and drier during the day, but cooler and more humid during the night (P < 0.05). No hut type effect was observed on sow use of the hut, posture, or nursing behaviour. Piglets showed greater expression of thermoregulating behaviour in the morning on day two in the Wood hut as it was the coolest (P = 0.03). Huddling was found to be the most common technique employed by piglets for thermoregulation in all huts, representing 61.2–73.8% of their time. Piglets were in contact with the sow 10.6–16.1% of the time while not nursing. The percentages of sows killing at least one piglet by crushing or trauma during the first week after farrowing were 93%, 86% and 43% for Wood, Plastic, and Metal huts, respectively (P = 0.02). Mortalities during the first week due to crushing or trauma were 18%, 15%, and 11% of liveborn piglets for the Wood, Plastic, and Metal huts, respectively (P = 0.44). The riskiest time for piglets, in terms of being crushed was found to be when the sow was standing (P = 0.04). This study suggests that the indoor risk factors for crushing change when sows are housed in huts. The Metal hut appears to be the best compromise considering thermal environment, behaviour, and litter survival, but the results suggest a need for future research into hut designs for farrowing sows on pasture to reduce crushing risks.

Effects of increasing levels of orange peel extract on kit growth, feed utilization, and some blood metabolites in the doe rabbits under heat stress conditions

One of the most severe consequences of climate change on the rabbit production sector is heat stress. Dietary supplementation of phytochemicals could alleviate the negative impact of heat stress on rabbits. Thirty-six V-line rabbit does with average live body weight (LBW) of 2.672 ± 0.031 kg were randomly allocated into three experimental groups as follows: the control group (OPE0) and the OPE2.5 and OPE5 groups were orally administered orange peel extract (OPE) at doses of 2.5 and 5 mL/doe. The increasing OPE levels significantly improved LBW at partum (p = 0.002) and weaning (p = 0.004), daily and total feed intake from pregnancy until weaning (p = 0.007), daily milk yield per doe at 7th and 14th days (p ≤ 0.05), and milk efficiency (p = 0.001). Litter size at 1st–28th days, litter weight gain, survival rate, and kit weight gain at 21st–28th days of heat-stressed doe rabbits were significantly improved with OPE treatments. The treatment of OPE5 significantly decreased serum glucose, triglycerides, and very-low-density lipoprotein-cholesterol levels of rabbits. The increasing OPE levels decreased significantly total lipid and low-density lipoprotein-cholesterol levels and increased (p = 0.001) high-density lipoprotein-cholesterol concentration in heat-stressed rabbits. In conclusion, the treatment of OPE improved feed utilization, milk efficiency, and reproductive performance and alleviated the drastic impacts of heat stress on rabbits.

Effect of different surgical methods in the mouse embryo transfer: Electrosurgery versus cold surgical technique effects on repeated use of surrogate mothers, pregnancy rate and post-surgical behavior.

Using the cold surgical technique (CST) is the most common practice to accomplish embryo transfer (ET). However, it can lead to uncontrolled bleeding and mortality in laboratory animals. Electrosurgery technique (EST) has provided the opportunity to prevent such complications. This study was aimed to evaluate CST versus EST in terms of repeated use of surrogate mothers, litter size, implantation rate and post-surgical behavior. Virgin female NMRI mice were allocated into two different surgical groups (n = 40): 1) CST-ET (control) and 2) EST-ET. Results showed that the first ET in EST-ET and CST-ET groups did not affect litter size, pregnancy rate and survival of surrogate mothers. Following the second and the third ETs, litter size was significantly affected through CST compared to EST, pregnancy rate and survival of surrogate mothers. Litter size, pregnancy rate and surrogate mothers survival rate did not show any significant reduction following the first and the second ETs in EST group. On the other hand, the third ET showed dramatic reduction for all aforementioned parameters regardless of the chosen surgical method for ET. Mice in EST-ET group did not show any significant change in their behavior indicating reduced well-being during the first 24 hr following the first, the second and the third ETs compared to CST-ET group. In conclusion, using EST for ET in mouse made it feasible to reuse surrogate mothers with minimum animal mortality; this could be pivotal with regard to reproductive and animal welfare aspects and research costs. Also, the results indicated that bleeding has severe diverse effects on ET efficiency.

Prenatal methadone exposure impairs adolescent cognition and GABAergic neurodevelopment in a novel rat model of maternal methadone treatment

Methadone maintenance treatment (MMT) is the most common treatment for opioid-dependent pregnant women worldwide. Despite its widespread use, MMT is associated with a variety of adverse neurodevelopmental outcomes in exposed offspring, particularly cognitive impairments. The neurobiological abnormalities underlying these cognitive impairments are, however, poorly understood. This is, in part, due to a lack of animal models that represents the standard of care that methadone is administered in the clinic, with inconsistencies in the timing, doses and durations of treatment. Here we describe the characterisation of a clinically relevant rat model of MMT in which the long-term behavioural and neurobiological effects of prenatal methadone exposure can be assessed in adolescent offspring. Female Sprague-Dawley rats were treated orally with an ascending methadone dosage schedule (5, 10, 15, 20, 25 and 30 mg/kg/day), self-administered in drinking water prior to conception, throughout gestation and lactation. Pregnancy success, maternal gestational weight gain, litter survival and size were not significantly altered in methadone-exposed animals. Methadone-exposed offspring body and brain weights were significantly lower at birth. Novel object recognition tests performed at adolescence revealed methadone-exposed offspring had impaired recognition memory. Furthermore, the rewarded T-maze alternation task demonstrated that methadone-exposed female, but not male, offspring also exhibit working memory and learning deficits. Immunoblots of the adolescent prefrontal cortex and hippocampus showed methadone-exposed offspring displayed reduced levels of mature BDNF, in addition to the GABAergic proteins, GAD67 and parvalbumin, in a sex- and brain region-specific fashion. This rat model closely emulates the clinical scenario in which methadone is administered to opioid-dependent pregnant woman and provides evidence MMT can cause cognitive impairments in adolescent offspring that may be underlined by perturbed neurodevelopment of the GABAergic system.

Gene therapy via canalostomy approach preserves auditory and vestibular functions in a mouse model of Jervell and Lange-Nielsen syndrome type 2

Mutations in voltage-gated potassium channel KCNE1 cause Jervell and Lange-Nielsen syndrome type 2 (JLNS2), resulting in congenital deafness and vestibular dysfunction. We conducted gene therapy by injecting viral vectors using the canalostomy approach in Kcne1−/− mice to treat both the hearing and vestibular symptoms. Results showed early treatment prevented collapse of the Reissner’s membrane and vestibular wall, retained the normal size of the semicircular canals, and prevented the degeneration of inner ear cells. In a dose-dependent manner, the treatment preserved auditory (16 out of 20 mice) and vestibular (20/20) functions in mice treated with the high-dosage for at least five months. In the low-dosage group, a subgroup of mice (13/20) showed improvements only in the vestibular functions. Results supported that highly efficient transduction is one of the key factors for achieving the efficacy and maintaining the long-term therapeutic effect. Secondary outcomes of treatment included improved birth and litter survival rates. Our results demonstrated that gene therapy via the canalostomy approach, which has been considered to be one of the more feasible delivery methods for human inner ear gene therapy, preserved auditory and vestibular functions in a dose-dependent manner in a mouse model of JLNS2.

Management, blood and reproductive parameters of rabbits reared in Imo State

The management, haematological, serum biochemical and reproductive parameters of rabbits reared in the 3 zones (Okigwe, Orlu and Owerri) of Imo State were investigated. Data for this study were collected through questionnaire, on-the-farm assessment and fluid sample (blood and semen) from the rabbits. The hutch/cage type of housing is the most prevalent in Imo State, constituting 73.58 %. Most rabbit farmers in Imo State (45.28 %) combine concentrate and forage in rabbit feeding, 47.17 % of the rabbit house/environment were fairly clean, 30.19 % dirty and 22.64 % were clean. Rabbits with ages ranging from 5 – 8 months recorded average live weight of 1.91 kg, while annual average kindling and litter size of rabbit does reared in Imo State were 5.67 and 7.43, respectively; with average litter survival rate of 60.16 % between parturition and weaning. Haematological analysis of the adult rabbits recorded 27.80 %, 9.56 g/dl and 3.40 x 106/ml in packed cell volume, haemoglobin concentration and red blood cell count, respectively, which were lower than normal reference values. Total serum protein, globulin and urea values were lower than normal reference values recording 4.44 g/dl, 1.57 g/dl and 16.56 mg/dl, respectively. Semen parameters obtained from adult rabbit bucks were inferior to semen parameters of adult rabbit bucks reared in similar geographical locations and environment, but under standard management practices. This study was therefore designed to assess the level of management, blood and reproductive parameters of rabbits in Imo State.

Hypothalamic Gene Expression and Postpartum Behavior in a Genetic Rat Model of Depression.

Postpartum depression is a complex illness that often occurs in genetically predisposed individuals. Closely related inbred rat strains are a great resource to identify novel causative genes and mechanisms underlying complex traits such as postpartum behavior. We report differences in these behaviors between the inbred depression model, Wistar Kyoto (WKY) More Immobile (WMI), and the isogenic control Wistar Kyoto Less Immobile (WLI) dams. WMI dams showed significantly lower litter survival rate and frequency of arched back and blanket nursing, but increased pup-directed licking, grooming, and retrieval during postpartum days (PPD) 1–10, compared to control WLIs. This increased pup-directed behavior and the frequency of self-directed behaviors segregated during selective breeding of the progenitor strain of WKY, which is also a depression model. These behaviors are manifested in the WMIs in contrast to those of WLIs. Furthermore, habitual differences in the self-directed behavior between light and dark cycles present in WLIs were missing in WMI dams. Hypothalamic transcript levels of the circadian rhythm-related gene Lysine Demethylase 5A (Kdm5a), period 2 (Per2), and the maternal behavior-related oxytocin receptor (Oxtr), vasopressin (Avp), and vasopressin receptor 1a (Avpr1a) were significantly greater in the post-weaning WMI dams at PPD 24 compared to those of WLIs, and also to those of WMI dams whose litter died before PPD 5. Expression correlation amongst genes differed in WLI and WMI dams and between the two time-points postpartum, suggesting genetic and litter-survival differences between these strains affect transcript levels. These data demonstrate that the genetically close, but behaviorally disparate WMI and WLI strains would be suitable for investigating the underlying genetic basis of postpartum behavior.

Perinatal diet influences health and survival in a mouse model of leukemia

The goal of the current study was to determine the role of maternal diet in the perinatal period on the health and survival of the offspring. AKR/J mice, a model described to be susceptible to leukemia development, was used where females were maintained on either standard diet (SD), high sucrose diet, Western diet, or calorie restriction (CR) as they were mated with SD-fed males. Body weights, pregnancy rates, litter size, and litter survival were used as markers of successful pregnancy and pup health. Data indicated that maternal diet had significant effects on litter size, early pup survival, and early pup body weights. As pups matured, the makeup of their respective maternal diet was a predictor of adult metabolic health and survival. Overall, these results suggest that perinatal maternal diet is an important determinant of the health and survival of the offspring and that these effects continue well into adulthood, strongly correlating with lifespan.

Effects of free feeding time system and energy level to improve the reproductive performance of lactating sows during summer.

The reproductive performance of lactating sows was investigated by using different feeding methods including conventional feeding (CF, 3 times/d) or free feeding (FF), and different dietary energy level including low energy (LE: 3,300) or high energy (HE: 3,400 kcal/kg) during the hot season. A total of twenty-eight crossbred (Yorkshire × Landrace) sows were distributed into four treatments as a 2 × 2 factorial arrangement. Sows in the FF group showed lower body weight and backfat loss (p < 0.05) compared with the CF group. Backfat loss during lactation was lower (p < 0.05) in sows fed HE diet than in that fed LE diet. There were no significant differences in litter survival rate and weaning to estrus interval, but the litter weight at weaning was improved (p < 0.05) in FF and HE sows. Hence, it is concluded that using the free-feeding system or increased dietary energy density leads to improved sow performance during hot ambient temperature.

Changes in genetic parameters for fitness and growth traits in pigs under genomic selection.

Genomic selection increases accuracy and decreases generation interval, speeding up genetic changes in the populations. However, intensive changes caused by selection can reduce the genetic variation and can strengthen undesirable genetic correlations. The purpose of this study was to investigate changes in genetic parameters for fitness traits related with prolificacy (FT1) and litter survival (FT2 and FT3), and for growth (GT1 and GT2) traits in pigs over time. The data set contained 21,269 (FT1), 23,246 (FT2), 23,246 (FT3), 150,492 (GT1), and 150,493 (GT2) phenotypic records obtained from 2009 to 2018. The pedigree file included 369,776 animals born between 2001 and 2018, of which 39,103 were genotyped. Genetic parameters were estimated with bivariate models (FT1-GT1, FT1-GT2, FT2-GT1, FT2-GT2, FT3-GT1, and FT3-GT2) using 3-yr sliding subsets. With a Bayesian implementation using the GIBBS3F90 program computations were performed as genomic analysis (GEN) or pedigree-based analysis (PED), that is, with or without genotypes, respectively. For GEN (PED), the changes in heritability from the first to the last year interval, that is, from 2009–2011 to 2015–2018 were 8.6 to 5.6 (7.9 to 8.8) for FT1, 7.8 to 7.2 (7.7 to 10.8) for FT2, 11.4 to 7.6 (10.1 to 7.5) for FT3, 35.1 to 16.5 (32.5 to 23.7) for GT1, and 35.9 to 16.5 (32.6 to 24.1) for GT2. Differences were also observed for genetic correlations as they changed from −0.31 to −0.58 (−0.28 to −0.73) for FT1-GT1, −0.32 to −0.50 (−0.29 to −0.74) for FT1-GT2, −0.27 to −0.45 (−0.30 to −0.65) for FT2-GT1, −0.28 to −0.45 (−0.32 to −0.66) for FT2-GT2, 0.14 to 0.17 (0.11 to 0.04) for FT3-GT1, and 0.14 to 0.18 (0.11 to 0.05) for FT3-GT2. Strong selection in pigs reduced heritabilities and emphasized the antagonistic genetic relationships between fitness and growth traits. With genotypes considered, heritability estimates were smaller and genetic correlations were greater than estimates with only pedigree and phenotypes. When selection is based on genomic information, genetic parameters estimated without this information can be biased because preselection is not accounted for by the model.

Maternal Microdeletion at the H19/Igf2 ICR in Mice Increases Offspring Susceptibility to In Utero Environmental Perturbation.

Deficiency of methyl donor nutrients folate, choline, and methionine (methyl deficiency) during gestation can impair fetal development and perturb DNA methylation. Here, we assessed genetic susceptibility to methyl deficiency by comparing effects in wildtype C57BL/6J (B6) mice to mutant mice carrying a 1.3 kb deletion at the H19/Igf2 Imprinting Control Region (ICR) (H19ICRΔ2,3). The H19ICRΔ2,3 mutation mimics microdeletions observed in Beckwith-Wiedemann syndrome (BWS) patients, who exhibit epimutations in cis that cause loss of imprinting and fetal overgrowth. Dams were treated during pregnancy with 1 of 4 methyl sufficient (MS) or methyl deficient (MD) diets, with or without the antibiotic commonly used to deplete folate producing gut microbes. As expected, after ~9 weeks of treatment, dams in MD and MD + antibiotic groups exhibited substantially reduced plasma folate concentrations. H19ICRΔ2,3 mutant lines were more susceptible to adverse pregnancy outcomes caused by methyl deficiency (reduced birth rate and increased pup lethality) and antibiotic (decreased litter size and litter survival). Surprisingly, pup growth/development was only minimally affected by methyl deficiency, while antibiotic treatment caused inverse effects on B6 and H19ICRΔ2,3 lines. B6 pups treated with antibiotic exhibited increased neonatal and weanling bodyweight, while both wildtype and mutant pups of heterozygous H19ICRΔ2,3/+ dams exhibited decreased neonatal bodyweight that persisted into adulthood. Interestingly, only antibiotic-treated pups carrying the H19ICRΔ2,3 mutation exhibited altered DNA methylation at the H19/Igf2 ICR, suggesting ICR epimutation was not sufficient to explain the altered phenotypes. These findings demonstrate that genetic mutation of the H19/Igf2 ICR increases offspring susceptibility to developmental perturbation in the methyl deficiency model, maternal and pup genotype play an essential role, and antibiotic treatment in the model also plays a key independent role.

PSXI-40 Body reserves profile and rearing performance of meat ewes are genetically linked

Abstract The objective of this work was to study the relationships between different body reserve (BR) dynamic profiles and ewe rearing performance (PERF) traits in a Romane meat sheep population extensively managed in a rangeland of France. Genetic parameters that link litter weight and lamb BW at lambing and weaning, lamb growth rate at 1, 2 and 3 months after lambing and litter survival from lambing to weaning to different BR profiles that have previously been demonstrated in the same animals are reported. Records from the flock of the INRA La Fage experimental farm were used to generate datasets from 14 lambing years (YR: 2002 to 2015). The datasets involved 1,146, 1,072 and 414 females belonging to 3 parities (PAR: 1, 2 and 3, respectively), with first lambing at 2 ages (AGE: 1 or 2-yr-old), and 4 litter sizes (LS: 1, 2, 3 and 4 lambs born alive). Significant effects on PERF were observed on all fixed variables considered (i.e., YR, AGE, PAR and LS). Similarly, the BW and BCS profiles of the ewes were strongly related to the PERFs across the 3 PARs studied, particularly for the BW profiles in the first cycle (PAR 1). In contrast to litter survival, which showed very low h² values and repeatabilities, the traits of lamb BW at lambing and weaning and litter weights at weaning had moderate h² values ranging from 0.20 to 0.23 and repeatabilities ranging from 0.21 to 0.27. In conclusion, our results show that genetic gains may be possible due to the inclusion of combined BR and PERF traits in sheep selection programs for this breed and warrant further research in other sheep populations.

Oral vitamin A supplementation of porcine epidemic diarrhea virus infected gilts enhances IgA and lactogenic immune protection of nursing piglets

Vitamin A (VA) has pleiotropic effects on the immune system and is critical for mucosal immune function and intestinal lymphocyte trafficking. We hypothesized that oral VA supplementation of porcine epidemic diarrhea virus (PEDV)-infected pregnant gilts would enhance the gut-mammary gland-secretory IgA axis to boost lactogenic immunity and passive protection of nursing piglets against PEDV challenge. Gilts received daily oral retinyl acetate (30 000 IU) starting at gestation day 76 throughout lactation. At 3–4 weeks pre-partum, VA-supplemented (PEDV + VA) and non-supplemented (PEDV) gilts were PEDV or mock inoculated (mock + VA and mock, respectively). PEDV + VA gilts had decreased mean PEDV RNA shedding titers and diarrhea scores. To determine if lactogenic immunity correlated with protection, all piglets were PEDV-challenged at 3–5 days post-partum. The survival rate of PEDV + VA litters was 74.2% compared with 55.9% in PEDV litters. Mock and mock + VA litter survival rates were 5.7% and 8.3%, respectively. PEDV + VA gilts had increased PEDV IgA antibody secreting cells and PEDV IgA antibodies in serum pre-partum and IgA+β7+ (gut homing) cells in milk post piglet challenge compared with PEDV gilts. Our findings suggest that oral VA supplementation may act as an adjuvant during pregnancy, enhancing maternal IgA and lactogenic immune protection in nursing piglets.