Decreased Pup Survival Research Articles

Cumulative adversity and survival in the wild.

Protecting populations contending with co-occurring stressors requires a better understanding of how multiple early-life stressors affect the fitness of natural systems. However, the complexity of such research has limited its advancement and prevented us from answering new questions. In human studies, cumulative risk models predict adult health risk based on early adversity exposure. We apply a similar framework in wild yellow-bellied marmots (Marmota flaviventer). We tested cumulative adversity indices (CAIs) across different adversity types and time windows. All CAIs were associated with decreased pup survival and were well supported. Moderate and acute, but not standardized CAIs were associated with decreased lifespan, supporting the cumulative stress hypothesis and the endurance of early adversity. Multivariate models showed that differences in lifespan were driven by weaning date, precipitation, and maternal loss, but they performed poorly compared with CAI models. We highlight the development, utility, and insights of CAI approaches for ecology and conservation.

Contributions from terrestrial and marine resources stabilize predator populations in a rapidly changing climate

AbstractClimate change has different and sometimes divergent effects on terrestrial and marine food webs, and in coastal ecosystems, these effects are tightly interlinked. Responses of opportunistic coastal predators and scavengers to climate change may thus be complex and potentially highly flexible, and can simultaneously serve as indicators of, and have profound impacts on, lower trophic levels. Gaining mechanistic understanding of these responses is therefore important, but often not feasible due to lack of long‐term data from marked individuals. Here, we used a Bayesian integrated population model (IPM) to elucidate the effects of arctic warming and concurrent changes in terrestrial and marine resource availability on population dynamics of the opportunistic arctic fox (Vulpes lagopus) in Svalbard. Joint analysis of four types of data (den survey, age‐at‐harvest, placental scars, mark‐recovery) revealed relatively stable population size and age structure over the last 22 yr (1997–2019) despite rapid environmental change linked to climate warming. This was related to the fact that terrestrial resources (reindeer carcasses, geese) became more abundant while the availability of marine resources (seal pups/carrion) decreased, and was driven by divergent trends in different vital rates (e.g., increased pregnancy rate but decreased pup survival). Balanced contributions of survival vs. reproduction and of immigration vs. local demography further stabilized population size. Our study thus sheds light on the mechanisms underlying population dynamics of opportunistic carnivores exploiting terrestrial and marine resources and suggests that exploitation of resources across different ecosystems can buffer predators against climate change. Additionally, it highlights the large potential of IPMs as tools to understand and predict the effects of environmental change on wildlife populations, even when data on marked individuals are sparse.

Risk assessment of chlorinated paraffins in feed and food.

The European Commission asked EFSA for a scientific opinion on the risks for animal and human health related to the presence of chlorinated paraffins in feed and food. The data for experimental animals were reviewed and the CONTAM Panel identified the liver, kidney and thyroid as the target organs for the SCCP and MCCP mixtures tested in repeated dose toxicity studies. Decreased pup survival and subcutaneous haematoma/haemorrhage were also identified as critical effects for an MCCP mixture. For the LCCP mixtures tested, the liver was identified as the target organ. The Panel selected as reference points a BMDL 10 of 2.3 mg/kg bw per day for increased incidence of nephritis in male rats, and of 36 mg/kg bw per day for increased relative kidney weights in male and female rats for SCCPs and MCCPs, respectively. For LCCPs, a reference point relevant for humans could not be identified. Due to the limitations in the toxicokinetic and toxicological database, the Panel concluded that derivation of a health‐based guidance value was not appropriate. Only limited data on the occurrence of SCCPs and MCCPs in some fish species were submitted to EFSA. No data were submitted for LCCPs. Thus, a robust exposure assessment and consequently a complete risk characterisation could not be performed. A preliminary risk characterisation based only on the consumption of fish was performed, and the calculated margins of exposure suggested no health concern for this limited scenario. The Panel noted that dietary exposure will be higher due to the contribution of CPs from other foods. The Panel was not able to identify reference points for farm animals, horses and companion animals. No occurrence data for feed were submitted to EFSA. Therefore, no risk characterisation could be performed for any of these animal species.

Exposure to systemic and intrauterine inflammation leads to decreased pup survival via different placental mechanisms

ProblemExposure to systemic maternal inflammation (i.e., maternal sepsis, influenza, human immunodeficiency virus, or pyelonephritis) and intrauterine (IU) inflammation (i.e., chorioamnionitis or preterm labor) have been associated with adverse perinatal sequelae. Whether systemic and localized inflammation leading to adverse outcomes have similar placental mechanisms remain unclear. Method of StudyWe conducted a study by murine modeling systemic and localized IU inflammation with injections of either intraperitoneal (IP) or IU interleukin-1β (IL-1β) and compared fetoplacental hemodynamic changes, cytokine/chemokine expression, and fetal loss. ResultsIU IL-1β exposure reduced offspring survival by 31.1% and IP IL-1β exposure by 34.5% when compared with control pups. Despite this similar outcome in offspring survival, Doppler analysis revealed a stark difference: IU group displayed worsened fetoplacental hemodynamic changes while no differences were found between IP and control groups. While both IU and IP groups had increases in pro-inflammatory cytokines and chemokines, specific gene expression trends differed between the two groups, once again highlighting their mechanistic differences. ConclusionWhile both IP and IU IL-1β exposure similarly affected pup survival, only IU inflammation resulted in fetoplacental hemodynamic changes. We speculate that exposure to maternal systemic and IU inflammation plays a key role in fetal injury by utilizing different placental inflammatory pathways and mechanisms.

Increased placental T cell trafficking results in adverse neurobehavioral outcomes in offspring exposed to sub-chronic maternal inflammation

Interleukin-1 beta (IL-1β) is a cytokine mediator of perinatal brain injury. The effect of sub-chronic systemic IL-1β exposure in perinatal and offspring outcomes is unclear. The aim of this study was to examine the effects of maternal IL-1β exposure on pregnancy and offspring outcomes. At E15, CD1 dams were allocated to receive intraperitoneal injection of phosphate buffered saline or mouse recombinant IL-1β (1 mcg) for four consecutive days. We analyzed pup survivaland neurobehavioral status. At E18, placental H&E staining and fetal brain Nissl staining was performed. Placental gene expression was analyzed by qPCR and T cell infiltration was analyzed by flow cytometry. Effects of inflammation on feto-placental blood flow were analyzed by Doppler ultrasonography. IL-1β decreased pup survival (P < .0001) and adversely affected offspring performance on neurodevelopmental tests (P < .05). Placentas of exposed dams exhibited significant thinning of maternal and fetal sides, and fetal brain exhibited cortical thinning. Placental qPCR analysis revealed significant upregulation of NFκB2 (P = .0021) and CXCL11 (P = .0401). While maternal IL-1β exposure did not affect feto-placental blood flow, placental flow cytometry showed an increase in placental infiltration of CD4+ T cells at 24 h post-injection (hpi, P < .0001) and CD8+ T cells at 72 hpi (P = .0217). Maternal sub-chronic, systemic inflammation with IL-1β decreased pup survival and played a key role in perinatal brain injury. The mechanisms behind these outcomes may involve immune system activation and alterations in placental T cell trafficking.

Wolf denning behaviour in response to external disturbances and implications for pup survival

We conducted a 15-year study (1999–2014) of wolf denning behavior in Naliboki Forest, Belarus, to determine the extent to which some external factors (rain, mosquitoes, human disturbances) and litter size are negatively correlated with pup survival until autumn.For this purpose we entirely documented denning areas of 30 breeding wolf pairs. Initial denning area includes the natal den site and (ii) secondary den sites between which the parent wolves transported sucessively the litter during the rearing season.The number of den sites per denning area ranged from 1 to 4. The distances in kilometres differed significantly between den sites. The total number of dens (surface dens and burrows) was higher in the natal den site compared with the other den sites. The number of surface dens per den site was higher compared with burrows in den sites 1, 2 and 3 but not den site 4. A total of 168 pups was found over the 15 years. Litter sizes ranged from 1 to 11 (average 5.6±1.9). The rate of pup survival ranged from 0 to 100% and averaged 54.5±29%.We examined the bivariate association between environmental conditions (mosquitoes, rainfall and human presence) and number of surface dens, total number of burrows and number of den sites. Environmental conditions were assessed from spring to mid-summer. Results show that there was a positive relationship between environmental conditions and number of den sites, and also that more difficult environmental conditions (rainy weather, many mosquitoes) decreased pup survival both in absolute and in relative terms. A cluster analysis showed that pup survival was also influenced by human presence. Wolves probably have a more complicated denning behaviour following stressful event which may lead to less effectiveness for feeding or protecting pups. The number of pups surviving was also found to be lower when there were many (8–10) pups because den shifting is more risky in this case. Burrows improve pup survival. Our results tend to suggest that, in our study area, a high mortality rate of wolf pups could be related to external and internal factors of stress.

Behavioral Deficits in Juveniles Mediated by Maternal Stress Hormones in Mice

Maternal depression has been shown to negatively impact offspring development. Investigation into the impact of maternal depression and offspring behavior has relied on correlative studies in humans. Further investigation into the underlying mechanisms has been hindered by the lack of useful animal models. We previously characterized a mouse model which exhibits depression-like behaviors restricted to the postpartum period and abnormal/fragmented maternal care (Gabrd −/− mice). Here we utilized this unique mouse model to investigate the mechanism(s) through which maternal depression-like behaviors adversely impact offspring development. Cross-fostering experiments reveal increased anxiety-like and depression-like behaviors in mice reared by Gabrd −/− mothers. Wild type and Gabrd −/− mice subjected to unpredictable stress during late pregnancy exhibit decreased pup survival and depression-like behavior in the postpartum period. Exogenous corticosterone treatment in wild type mice during late pregnancy is sufficient to decrease pup survival and induce anxiety-like and depression-like behaviors in the offspring. Further, the abnormal behaviors in juvenile mice reared by Gabrd −/− mice are alleviated by treatment of the mothers with the corticotropin-releasing hormone (CRH) antagonist, Antalarmin. These studies suggest that hyperresponsiveness of the HPA axis is associated with postpartum depression and may mediate the adverse effects of maternal depression on offspring behavior.

Ivermectin treatment of free-ranging endangered Australian sea lion (Neophoca cinerea) pups: effect on hookworm and lice infection status, haematological parameters, growth, and survival.

A placebo-controlled study was used to investigate the effectiveness of ivermectin to treat hookworm (Uncinaria sanguinis) and lice (Antarctophthirus microchir) infections in free-ranging Australian sea lion (Neophoca cinerea) pups and to test the hypotheses that these parasitic infections cause anaemia, systemic inflammatory responses, and reduced growth, and contribute towards decreased pup survival. Ivermectin was identified as an effective and safe anthelmintic in this species. Pups administered ivermectin had significantly higher erythrocyte counts and significantly lower eosinophil counts compared to controls at 1-2months post-treatment, confirming that U. sanguinis and/or A. microchir are causatively associated with disease and demonstrating the positive effect of ivermectin treatment on clinical health parameters. Higher growth rates were not seen in ivermectin-treated pups and, unexpectedly, relatively older pups treated with ivermectin demonstrated significantly reduced growth rates when compared to matched saline-control pups. Differences in survival were not identified between treatment groups; however, this was attributed to the unexpectedly low mortality rate of recruited pups, likely due to the unintended recruitment bias towards pups >1-2months of age for which mortality due to hookworm infection is less likely. This finding highlights the logistical and practical challenges associated with treating pups of this species shortly after birth at a remote colony. This study informs the assessment of the use of anthelmintics as a tool for the conservation management of free-ranging wildlife and outlines essential steps to further the development of strategies to ensure the effective conservation of the Australian sea lion and its parasitic fauna.

Maternal surfactant protein A influences the immunoprotective properties of milk in a murine model

Maternal surfactant protein A (SP-A), a collectin with innate immune system function, is critical to newborn mouse survival preventing bacterial peritonitis associated with a nonhygienic environmental exposure. We hypothesized that SP-A improves newborn survival by optimizing milk immunoprotection. Regional (lung) and systemic (milk and serum) immunologic responses to a novel antigen, 2,4-dintirophenyl keyhole limpet hemocyanin (DNP-KLH), and to a nonhygienic environment were evaluated in wild-type (WT) and SP-A null murine dams. Cross-fostering pups assessed the impact of milk on newborn survival. Maternal SP-A optimized antigen-specific milk secretory IgA (sIgA) production following the DNP-KLH exposure. Milk total and environment-specific sIgA production was not dependent on maternal SP-A in the nonhygienic exposure. At baseline, SP-A null milk contained physiologically meaningful increases in two proinflammatory cytokines compared with WT milk. The lack of SP-A plus the nonhygienic environmental exposure synergistically increased the number of proinflammatory cytokines contained in milk. Finally, the SP-A null genotype decreased pup survival during a nonhygienic environmental exposure. Maternal SP-A impacts milk sIgA and cytokine content, and is associated with improved newborn health.

Protein restriction during fetal and neonatal development in the rat alters reproductive function and accelerates reproductive ageing in female progeny

Recent studies demonstrate long-term programming of function of specific organ systems resulting from suboptimal environments during fetal life and development up to weaning. Nutrient restriction during pregnancy and lactation impairs overall fetal growth and development. We determined the effects of maternal protein restriction (MPR; 50% normal protein intake) during fetal development and/or lactation in rats on the function and ageing of the reproductive system of female progeny. Rats were fed either a control 20% casein diet (C) or a restricted diet (R) of 10% casein during pregnancy. After delivery mothers received either C or R diet until weaning to provide four groups, CC, RR, CR and RC. We report data on female offspring only. After weaning pups were fed the C diet. MPR increased maternal progesterone, corticosterone, oestradiol and testosterone concentrations at 19 days gestation. Reproductive and somatic phenotype was altered as pup birth weight was decreased, and ano-genital distance was increased by MPR. Pup corticosterone was decreased at 2 days postnatal (PN) life. Vaginal opening and timing of the first oestrus were delayed in RR and CR and these differences were not related to body weight. At 21 days PN oestradiol in RR and CR and progesterone in RR were reduced; at 70 days PN luteinizing hormone (LH) in all restricted groups was reduced in dioestrus while follicle stimulating hormone (FSH) was unchanged. Cycle length increased between 140 days and 1 year in RR and CR but remained unchanged in CC, providing evidence of premature ageing of reproductive function. Fertility rates declined over the same period in the three experimental groups but not CC. MPR in one of the two experimental periods, either pregnancy or lactation, resulted in decreased pup survival compared with CC and RR. These data show that MPR results in delayed sexual maturation and premature ageing of reproductive function.

Fathers, Fat, and Maternal Energetics in a Biparental Hamster: Paternal Presence Determines the Outcome of a Current Reproductive Effort and Adipose Tissue Limits Subsequent Reproductive Effort

Djungarian hamster females, Phodopus campbelli, are severely constrained in their ability to reproduce successfully and lose 20% of their body weight by the time pups are weaned. In the wild and in the laboratory, biparental care improves maternal reproductive success. Two experiments quantified the effects of paternal presence and partial lipectomy [surgical depletion of parametrial white adipose tissue (PWAT) on day 8 of the 18-day gestation] on maternal energy balance, reproductive success, and investment in a subsequent reproductive attempt. Paired females reproduced successfully, maintained body weight, and invested in a second litter. Removal of the male decreased pup survival, growth, and readiness for dispersal by 18 days of age. Solitary females lost 10% of their body weight by the birth and a further 10% by day 18 after the birth. Thus, paternal presence balanced maternal energy budgets during reproduction and prevented a 20% loss in body weight. Equivalent weight loss occurs in response to other maternal stressors, therefore 20% may be the maximum tolerable weight loss in this species. Fresh weight of interscapular brown adipose tissue was predicted by the extent of maternal hyperthermia but not by maternal energy balance or lipectomy. Partial lipectomy did not adversely affect the female or the first litter but decreased the probability of investment in a second reproductive attempt and halved the size of the second litter. This effect may have been due to the 0.1% of body weight amount of lipid removed or may reflect a specialized role for PWAT in adjusting maternal investment.

Influence of different social partners on the survival and growth of pups in two species of Calomys (Muridae Sigmodontinae)

In this paper we investigated if the contact of a mother-pups unit with different partners may affect pup survival and growth in Calomys musculinus and C. laucha. Mother-pups units were housed with either a virgin female, a familiar male or a strange male, and the effect of these partners on the litter was measured from birth through weaning. In C. laucha both the presence of a strange male or a virgin female was deleterious for pup survival and growth. In C. musculinus, however, the presence of any partner, even the siring male, decreased pup survival and growth (the strange male was the most deleterious for pup growth). In both species the virgin female partner was killed in approximately half of the cases, while there was a differential response to the strange male, C. laucha females appeared less tolerant to strange males than their C. musculinus counterpart, which is consistent with the idea that C. musculinus females interact in nature with more than one male in their home range. All of the familiar males survived. This study provides evidence that C. laucha pups grow better in the presence of either the mother alone or in the partnership of the familiar male, while in C. musculinus, the presence of any partner, even the siring male, is deleterious for litter survival and growth under laboratory conditions. In the context of previous evidence, the current results are interpreted to mean that C. laucha is closer than C. musculinus to the monogamy end of a three-dimensional system for the definiton of monogamy.

Toxicologic studies on 2,4-dichlorophenyl- p-nitrophenyl ether

Studies on 2,4-dichlorophenyl- p-nitrophenyl ether (TOK ®, a new selective herbicide, were undertaken in several animal species to characterize its toxicity. In rats, the single po LD50 ± SD value for technical grade TOK (95%) was 2.63 ± 0.13 g/kg as compared to 3.58 ± 0.14 g/kg for 100% TOK. It did not produce skin irritation in rabbits or cutaneous sensitization in guinea pigs. Rats on dietary levels of 100 and 500 ppm for 13 wk, and on 10, 100, and 1000 ppm for 97 wk, showed no definite differences in growth, feed consumption, and mortality, as compared to respective controls. In the 13-wk study in rats, liver-to-body weight ratios at all dietary levels of TOK, except for males on 100 ppm, were significantly higher. Kidney ratios were elevated for female rats on 12,500 ppm and above and for male rats on 2,500 and 12,500 ppm. In the 97-wk study, organ-tobody weight ratios showed significant increases for kidneys and liver for male rats only on the 1000 ppm diet. No dose-related effects were noted on hemograms, urinary findings, and in microscopic examination of tissues in both the subchronic and chronic studies. In a 2-yr study in dogs given 20, 200, and 2000 ppm diets, no adverse trends were noted on growth, feed consumption, hematology, urinary findings, BSP, SGOT, SAP, BUN, and histopathologic findings. Significantly higher liver-to-body weight ratios appeared only in dogs on the 2000 ppm diet. Three-generation reproduction studies in rats throughout 2 mating cycles revealed no adverse trends in fertility, gestation, viability, and lactation indices for rats on 10 and 100 ppm diets; however, 1000 ppm diet affected the incidence of stillbirths and decreased pup survival, to a point where no pups were available for the F 1b generation, and 100 ppm caused some increase in stillbirths. Overall, in these studies, the highest no-effect level found was 10 ppm.

Toxicity of some benzodiazepine compounds with CNS activity

Acutely in rodents by oral and intraperitoneal routes, chlordiazepoxide was 2–3 times as toxic as diazepam, and diazepam was at least 3 times as toxic as oxazepam. Rats fed 0.06 or 0.12% for 20 weeks or 0.25% drug-diet for 6 weeks demonstrated little difference among the compounds. Histopathologically oxazepam produced minimal increase in liver fat while chlordiazepoxide and diazepam produced increased renal tubular pigmentation. Dogs dosed orally with 60–80, 120–127, or 200–240 mg/kg daily for 4 weeks did not die with oxazepam, but 6 died with 200 mg/kg chlordiazepoxide and 1 with 200 mg/kg diazepam. Sedation was greater with the latter 2 compounds. High serum alkaline phosphatase (SAP) and/or serum cholesterol occurred in a few dogs treated with 240 mg/kg oxazepam but in nearly all treated with chlordiazepoxide or diazepam, accompanied in the latter by elevation of sulfobromophthalein (BSP), serum glutamic oxaloacetic transaminase (SGOT), and serum glutamic pyruvic transaminase (SGPT), and decreased blood sugar. Histopathologically, only slight prostatic atrophy was found with oxazepam. Prostatic and gonadal changes were observed with chlordiazepoxide, and liver, renal, and gonadal alterations with diazepam. Rats fed 0.06, 0.25, or 0.5% oxazepam for 6 weeks or 0.015, 0.03, 0.06, or 0.12% for 55–56 weeks, and dogs given 15, 30, 60, or 120 mg/kg oxazepam orally for 52 weeks, 240 or 480 mg/kg for 10 weeks, or 960 mg/kg for 4 weeks exhibited minimal toxicity. Two dogs died at 960 mg/kg; other changes were similar to those reported for oxazepam above. Treatment of male and female parent rats with oxazepam before and throughout 2 mating cycles and female parent rats and rabbits from days 8–16 of the gestation period did not produce drug-related differences or abnormalities in the offspring. Treatment of parent female mice throughout gestation affected the incidence of stillbirths and decreased pup survival; 7 days premating treatment showed an apparent effect on fertility.