Breeding phenology drives variation in reproductive output, reproductive costs and offspring fitness in a viviparous ectotherm.

Phenological advances are a widespread response to global warming and can contribute to determine the climate vulnerability of organisms, particularly in ectothermic species which are highly dependent on ambient temperatures to complete their life cycle. Yet, the relative contribution of breeding dates and temperature conditions during gestation on fitness of females and their offspring is poorly documented in reptiles. Here, we exposed females of the common lizard Zootoca vivipara to contrasting thermal scenarios (cold versus hot treatment) during gestation and quantified effects of parturition dates and thermal treatment on life-history traits of females and their offspring for one year. Overall, our results suggest that parturition date has a greater impact than thermal conditions during gestation on life history strategies. In particular, we found positive effects of an earlier parturition date on juvenile survival, growth and recruitment suggesting that environmental dependent selection and/or differences in parental quality between early and late breeders underlie seasonal changes in offspring fitness. Yet, an earlier parturition date compromised the energetic condition of gravid females, which suggests the existence of a mother-offspring conflict regarding the optimisation of parturition dates. While numerous studies focused on the direct effects of alterations in incubation temperatures on reptile life-history traits, our results highlight the importance of considering the role of breeding phenology in assessing the short- and long-term effects of thermal developmental plasticity.

Effects of maternal advanced lipoxidation end products diet on the glycolipid metabolism and gut microbiota in offspring mice.

Introduction: Dietary advanced lipoxidation end products (ALEs), which are abundant in heat-processed foods, could induce lipid metabolism disorders. However, limited studies have examined the relationship between maternal ALEs diet and offspring health. Methods: To investigate the transgenerational effects of ALEs, a cross-generation mouse model was developed. The C57BL/6J mice were fed with dietary ALEs during preconception, pregnancy and lactation. Then, the changes of glycolipid metabolism and gut microbiota of the offspring mice were analyzed. Results: Maternal ALEs diet not only affected the metabolic homeostasis of dams, but also induced hepatic glycolipid accumulation, abnormal liver function, and disturbance of metabolism parameters in offspring. Furthermore, maternal ALEs diet significantly upregulated the expression of TLR4, TRIF and TNF-α proteins through the AMPK/mTOR/PPARα signaling pathway, leading to dysfunctional glycolipid metabolism in offspring. In addition, 16S rRNA analysis showed that maternal ALEs diet was capable of altered microbiota composition of offspring, and increased the Firmicutes/Bacteroidetes ratio. Discussion: This study has for the first time demonstrated the transgenerational effects of maternal ALEs diet on the glycolipid metabolism and gut microbiota in offspring mice, and may help to better understand the adverse effects of dietary ALEs.

Association between childhood family structure and longitudinal health behaviour changes in adulthood -Northern Finland birth cohort 1966 study.

BACKGROUND: Childhood family structure is considered to play a role in person's health and welfare. This study investigated the relationships between the longitudinal changes of adult health behaviours and childhood family structure. METHODS: From Northern Finland Birth Cohort 1966 questionnaires, we collected data on childhood family structure at the age of 14 ('two-parent family', 'one parent not living at home/no information on father', and 'father or mother deceased'), and on health behaviours (smoking, alcohol consumption and physical activity status) at the ages of 31 and 46. We used the multinomial logistic regression model to estimate the unadjusted and adjusted associations between childhood family structures and the longitudinal changes between 31 and 46 years of health behaviours (four-category variables). RESULTS: Of the study sample (n = 5431; 55.5% females), 7.1% of the offspring were represented in the 'One parent not living at home/no information on father' subgroup, 6.3% in the 'Father or mother deceased' subgroup and 86.6% in the 'Two-parent family'. 'One parent not living at home/no information on father' offspring were approximately twice as likely to smoke (adjusted OR 2.19, 95% CI 1.70-2.81) and heavily consume alcohol (adjusted OR 1.99, 95% CI 1.25-3.16) at both times in adulthood, relative to not smoking or not heavily consume alcohol, and compared with 'two-parent family' offspring. We found no statistically significant associations between childhood family structure and physical activity status changes in adulthood. CONCLUSIONS: Our findings suggest that the offspring of single-parent families in particular should be supported in early life to diminish their risk of unhealthy behaviours in adulthood.

Development of an animal model of hypothyroxinemia during pregnancy in Wistar rats.

BACKGROUND: Hypothyroxinemia is a subclinical thyroid hormone deficiency in which the mother has inadequate levels of T4 during pregnancy. The fetus relies entirely on the mother's T4 hormone level for early neurodevelopment. Isolated maternal hypothyroxinemia (IMH) in the first trimester of pregnancy can lead to lower intelligence, lower motor scores, and a higher risk of mental illness in descendants. Here, we focus on the autism-like behavior of IMH offspring. METHODS: The animals were administered 1 ppm of propylthiouracil (PTU) for 9 weeks. Then, the concentrations of T3, T4, and thyroid-stimulating hormone (TSH) were detected using enzyme-linked immunosorbent assay (ELISA) to verify the developed animal model of IMH. We performed four behavioral experiments, including the marble burying test, open-field test, three-chamber sociability test, and Morris water maze, to explore the autistic-like behavior of 40-day-old offspring rats. RESULTS: The ELISA test showed that the serum T3 and TSH concentrations in the model group were normal compared with the negative control group, whereas the T4 concentration decreased. In the behavioral experiments, the number of hidden marbles in the offspring of IMH increased significantly, the frequency of entering the central compartment decreased, and the social ratio decreased significantly. CONCLUSION: The animal model of IMH was developed by the administration of 1 ppm of PTU for 9 weeks, and there were autistic-like behavior changes such as anxiety, weakened social ability, and repeated stereotyping in the IMH offspring by 40 days.

The SIRT3/GSK-3ß/GLUT4 axis might be involved in maternal hypoxia-induced skeletal muscle insulin resistance in old male rat offspring.

Maternal hypoxia is strongly linked to insulin resistance (IR) in adult offspring, and altered insulin signaling for muscle glucose uptake is thought to play a central role. However, whether the SIRT3/GSK-3ß/GLUT4 axis is involved in maternal hypoxia-induced skeletal muscle IR in old male rat offspring has not been investigated. Maternal hypoxia was established from Days 5 to 21 of pregnancy by continuous infusion of nitrogen and air. The biochemical parameters and levels of key insulin signaling molecules of old male rat offspring were determined through a series of experiments. Compared to the control (Ctrl) old male rat offspring group, the hypoxic (HY) group exhibited elevated fasting blood glucose (FBG) (∼30%), fasting blood insulin (FBI) (∼35%), total triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-C), as well as results showing impairment in the glucose tolerance test (GTT) and insulin tolerance test (ITT). In addition, hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM) revealed impaired cellular structures and mitochondria in the longitudinal sections of skeletal muscle from HY group mice, which might be associated with decreased SIRT3 expression. Furthermore, the expression of insulin signaling molecules, such as GSK-3ß and GLUT4, was also altered. In conclusion, the present results indicate that the SIRT3/GSK-3ß/GLUT4 axis might be involved in maternal hypoxia-induced skeletal muscle IR in old male rat offspring.

Maternal asthma during pregnancy and risks of allergy and asthma in progeny: A systematic review and meta-analysis.

BACKGROUND: Clinical and preclinical evidence indicate that in utero maternal asthma exposure increases progeny asthma risk. Whether maternal asthma also increases the risks of progeny allergy is unclear. OBJECTIVES: To synthesise the available evidence on the relationship between in utero exposure to maternal asthma and postnatal asthma, wheezing and allergic diseases (Prospero: CRD42020201538). SEARCH STRATEGY: We systematically searched MEDLINE [PubMed], Embase [Ovid], Web of Science, Informit Health, the Cochrane Library, CINAHL [EBSCOhost], MedNar [Deep Web Technologies], ProQuest Theses and Dissertations, Scopus [Elsevier] and Trove, to the end of 2023. SELECTION CRITERIA: Studies reporting asthma, wheeze and/or allergic disease in progeny of women with and without asthma or with asthma classified by control, exacerbation or severity. DATA COLLECTION AND ANALYSIS: Double screening, selection, data extraction and quality assessment were performed, using Joanna Briggs Institute (JBI) scoring. MAIN RESULTS: Of 134 non-overlapping studies, 127 were included in ≥1 meta-analysis. Maternal asthma ever was associated with greater risks of asthma (65 studies, risk ratio [95% confidence interval] 1.76 [1.57-1.96]), wheeze (35 studies, 1.59 [1.52-1.66]), food allergy (5 studies, 1.32 [1.23-1.40]), allergic rhinitis (7 studies, 1.18 [1.06-1.31]) and allergic dermatitis (14 studies, 1.17 [1.11-1.23]) ever in progeny. Asthma during the pregnancy, more severe, and uncontrolled maternal asthma were each associated with greater risks of progeny asthma. CONCLUSIONS: Children of mothers with asthma are at increased risk for the development of allergic diseases. Whether improved maternal asthma control reduces risks of child allergy as well as asthma requires further investigation.

The impact of obesity surgery on newborn anthropometrics in women with and without polycystic ovary syndrome.

PURPOSE: Obesity surgery and polycystic ovary syndrome (PCOS) are both associated with increased risk of intrauterine growth restriction. We investigated whether offspring of mothers with PCOS who underwent obesity surgery had an increased risk of deviating birth anthropometrics compared to offspring of mothers without PCOS. METHODS: In this observational study, data from two study databases (BAROBS and PregMet2) were supplemented with data from patient's records from secondary and tertiary hospitals. In total, 162 offspring born to mothers with PCOS (n = 48) and without PCOS (n = 114) were included. Forty-nine offspring were born prior to, and 113 after obesity surgery. RESULTS: Mean ± SD birthweight (BW), birth length (BL), and head circumference (HC) before and after surgery for offspring born to mothers with PCOS were 3987 ± 495 g vs 3396 ± 526 g (P = 0.001), 52.2 ± 1.6 cm vs 50.1 ± 2.2 cm (P = 0.010), and 36.3 ± 1.97 cm vs 35.3 ± 1.66 cm (P = 0.183), respectively. In the non-PCOS group BW, BL and HC before and after were 3859 ± 603 g vs 3490 ± 538 g (P = 0.001), 51.3 ± 2.0 cm vs 49.9 ± 2.5 cm (P = 0.013), and 36.4 ± 2.0 cm vs 35.3 ± 1.8 cm (P = 0.016), respectively. Post-surgery, we found no difference in z-score BW, (∆-0.08, P = 0.677), BL (∆0.21, P = 0.184), and HC (∆0.14, P = 0.476) between children of PCOS and non-PCOS mothers. COMCLUSION: Babies born after obesity surgery were smaller and shorter in both the PCOS and non-PCOS group. Post-surgery anthropometrics were similar in babies born to mothers with and without PCOS.

Mental health outcomes of offspring exposed to parental intimate partner violence in Rwanda.

BACKGROUND: Children who witness parental intimate partner violence (IPV) are more likely to develop mental health issues compared to those who do not witness such violence. OBJECTIVE: The main objective of this study is to assess the association between parental intimate partner violence and child mental health outcomes. METHODOLOGY: This cross-sectional study involved 548 participants divided into two groups: parents (N = 304) and offspring (N = 244). The participants were recruited from Mageragere Sector in the City of Kigali (urban), as well as Mbazi and Ruhashya sectors in Huye District (rural). To assess the difference about mental difficulties reported by the offspring, a Mann-Whitney U test was employed to compare the responses of parents and their children on mental health outcomes. Additionally, multiple linear regression analysis was conducted to explore the association between parental intimate partner violence (IPV) and the mental health outcomes of their offspring. RESULTS: The results highlighted significant levels of mental and emotional challenges in children, as reported by both parents and the children themselves. Depression and youth conduct problems were more prevalent among the children compared to their parents, whereas anxiety and irritability were more commonly reported by parents than by their children. Intimate partner violence showed to be a predictor of irritability and anxiety symptoms in offspring. In terms of irritability, depression, and youth conduct problems they were identified as predictors of anxiety symptoms. Particularly, anxiety and irritability were revealed to predict youth conduct problems. CONCLUSION: The study indicates that parental intimate partner violence (IPV) has an impact on the mental well-being of their offspring. Furthermore, it was observed that there is not only a correlation between IPV and poor mental health outcomes, but also a connection between different mental conditions, implying that children exposed to IPV are more prone to experiencing a range of mental issues. As a result, intervention programs should place emphasis on addressing the mental disorders of both parents and children.

Maternal vitamin D levels during pregnancy and offspring schizophrenia.

BACKGROUND: Findings from previous studies on maternal 25(OH)D levels during pregnancy and offspring schizophrenia are limited and inconsistent. METHODS: We used nationwide population-based register data with a nested case-control design to examine the association between maternal 25(OH)D levels during pregnancy and offspring schizophrenia. The cases of schizophrenia (n = 1145) were born from 1987 to 1997, and received a diagnosis of schizophrenia by 2017, and were matched with equal number of controls. A quantitative immunoassay was used to measure maternal 25(OH)D in archived maternal serum in the national biobank of the Finnish Maternity Cohort, collected during the first and early second trimesters. Conditional logistic regression models examined the association between maternal 25(OH)D levels and offspring schizophrenia. RESULTS: No significant association was found between log-transformed maternal 25(OH)D levels and schizophrenia in unadjusted (OR 0.96, 95 % CI 0.78-1.17, p = 0.69) or adjusted analyses (aOR 0.98, 95 % CI 0.79-1.22, p = 0.89). Analyses by quintiles also revealed no association between the lowest quintile of maternal 25(OH)D levels and schizophrenia (OR 1.09, 95 % CI 0.81-1.45, p = 0.55; aOR 1.06, 95 % CI 0.78-1.45, p = 0.71). Maternal 25(OH)D levels, measured in categories, either in deficient category (OR 1.07 (0.85-1.35), p = 0.52; aOR 1.05 (0.81-1.34), p = 0.88) or insufficient category (OR 1.13, 95 % CI 0.92-1.40, p = 0.23; aOR 1.13, 95 % CI 0.90-1.41, p = 0.27) were also not associated with offspring schizophrenia. CONCLUSIONS: Maternal vitamin D levels in early pregnancy were not associated with offspring schizophrenia. Future studies measuring vitamin D during different stages of gestation are needed to draw firm conclusions.

Sex-dependent susceptibility to brain metabolic dysfunction and memory impairment in response to pre- and postnatal high-fat diet.

The developing brain is sensitive to the impacts of early-life nutritional intake. This study investigates whether maternal high fat diet (HFD) causes glucose metabolism impairment, neuroinflammation, and memory impairment in immature and adult offspring, and whether it may be affected by postweaning diets in a sex-dependent manner in adult offspring. After weaning, female rats were fed HFD (55.9% fat) or normal chow diet (NCD; 10% fat) for 8 weeks before mating, during pregnancy, and lactation. On postnatal day 21 (PND21), the male and female offspring of both groups were split into two new groups, and NCD or HFD feeding was maintained until PND180. On PND21 and PND180, brain glucose metabolism-, inflammation-, and Alzheimer's pathology-related markers were by qPCR. In adult offspring, peripheral insulin resistance parameters, spatial memory performance, and brain glucose metabolism (18F-FDG-PET scan and protein levels of IDE and GLUT3) were assessed. Histological analysis was also performed on PND21 and adult offspring. On PND21, we found that maternal HFD affected transcript levels of glucose metabolism markers in both sexes. In adult offspring, more profoundly in males, postweaning HFD in combination with maternal HFD induced peripheral and brain metabolic disturbances, impaired memory performance and elevated inflammation, dementia risk markers, and neuronal loss. Our results suggest that maternal HFD affects brain glucose metabolism in the early ages of both sexes. Postweaning HFD sex-dependently causes brain metabolic dysfunction and memory impairment in later-life offspring; effects that can be worsened in combination with maternal HFD.

Effects of Chicory (Cichorium intybus L.) Extract on Male Rat Reproductive System, Pregnancy and Offspring Development.

BACKGROUND: We recently reported that extract prepared from the aerial part of Cichorium intybus L. (CE) possesses hepatoprotective, hypolipidemic, and hypoglycemic properties. This paper focuses on the effects of CE on the male rat reproductive system and the effects of this treatment on pregnancy and offspring development. METHODS: The experimental male rats received 100 mg/kg bw/day, 500 mg/kg bw/day, and 1000 mg/kg bw/day of CE orally for 60 consecutive days. Rats that received tap water were used as controls. After treatment, we evaluated the effects of CE on the male reproductive system, fertility, and offspring development. RESULTS: For CE-treated male rats, there was a significant increase in the (1) diameter of seminiferous tubules, (2) spermatogenic index, (3) number of total and motile spermatozoa, and (4) testosterone levels. Additionally, there was a decrease in the pre- and post-implantation death of the embryos in the CE-treated group. All pups born from CE-treated males demonstrated normal development. CONCLUSIONS: CE treatment significantly improved male reproductive functions. No adverse effects on pregnancy and offspring development were observed when males were treated with CE. Further clinical evaluation of CE should lead to the development of a safe and effective phytodrug for treating male infertility.

The association of maternal smoking around birth with chronic respiratory diseases in adult offspring: A Mendelian randomization study.

INTRODUCTION: Maternal smoking during pregnancy disturbs fetal lung development, and induces in their offspring childhood respiratory diseases. Whether it has a continued impact on offspring adult lung health and exerts a casual effect of chronic respiratory diseases (CRDs), remains uncertain. We seek to determine the causal relationships between maternal smoking around birth and offspring adult CRDs, using summary data from previously described cohorts. METHODS: Mendelian randomization (MR) study was used to analyze the genome-wide associations of maternal smoking around birth and offspring adult CRDs, including respiratory insufficiency, chronic obstructive pulmonary disease (COPD), related respiratory insufficiency, emphysema, COPD, COPD hospital admissions, early onset of COPD, later onset of COPD, asthma, idiopathic pulmonary fibrosis (IPF), lung cancer (LC), small cell lung carcinoma (SCLC), and lung squamous cell carcinoma (LUSC). RESULTS: After removing single-nucleotide polymorphisms (SNPs) associated with smoking by the offspring, maternal smoking around birth was associated with increased risk of offspring adult respiratory diseases (OR=1.14; 95% CI: 1.013-1.284; p=0.030), respiratory insufficiency (OR=2.413; 95% CI: 1.039-5.603; p=0.040), COPD (OR=1.14; 95% CI: 1.013-1.284; p=0.003), and asthma (OR=1.336; 95% CI: 1.161-1.538; p<0.001). Besides, maternal smoking during pregnancy was associated with a greater risk of LUSC (OR=1.229; 95% CI: 0.992-1.523; p=0.059) than the risk of IPF (OR=1.001; 95% CI: 0.999-1.003; p=0.224), LC (OR=1.203; 95% CI: 0.964-1.501; p=0.103), or SCLC (OR=1.11; 95% CI: 0.77-1.601; p=0.577). CONCLUSIONS: In this MR analysis, maternal smoking around birth caused a strong risk factor for the offspring to develop lung problems and CRDs in adulthood. The policy related to smoking cessation for mothers during pregnancy should be encouraged.

Morphological and histopathological changes of maternal levetiracetam on the cerebellar cortex of the offspring of albino rat.

Levetiracetam (LEV) is being used by women with reproductive-age epilepsy at a significantly higher rate. The purpose of the study was to assess how levetiracetam treatment during pregnancy affected the offspring's weight and cerebellum. Forty pregnant rats were divided into two groups (I, II). Two smaller groups (A, B) were created from each group. The rats in group I were gavaged with approximately 1.5 mL/day of distilled water either continuously during pregnancy (for subgroup IA) or continuously during pregnancy and 14 days postpartum (for subgroup IB). The rats in group II were gavaged with about 1.5 mL/day of distilled water (containing 36 mg levetiracetam) either continuously during pregnancy (for subgroup IA) or continuously during pregnancy and 14 days postpartum (for subgroup IB). After the work was completed, the body weight of the pups in each group was recorded, and their cerebella were analyzed histologically and morphometrically. Following levetiracetam treatment, the offspring showed decreased body weight and their cerebella displayed delayed development and pathological alterations. These alterations manifested as, differences in the thicknesses of the layers of cerebellar cortex as compared to the control groups; additionally, their cells displayed cytoplasmic vacuolation, nuclear alterations, fragmented rough endoplasmic reticulum and lost mitochondrial cristae. Giving levetiracetam to pregnant and lactating female rats had a negative impact on the body weight and cerebella of the offspring. Levetiracetam should be given with caution during pregnancy and lactation.

Metabolic Profile of Offspring of Mothers with Gestational Diabetes Mellitus.

Introduction: Gestational diabetes mellitus (GDM) is defined as diabetes diagnosed in the second or third trimester of pregnancy that was not clearly overt diabetes before gestation. Unrecognized and untreated GDM confers significantly greater maternal and fetal risk, which is largely related to the degree of hyperglycemia. The specific risks of diabetes in pregnancy include but are not limited to, spontaneous abortion, pre-eclampsia, fetal anomalies, macrosomia, neonatal hypoglycemia, hyperbilirubinemia, and respiratory distress syndrome. Additionally, GDM is also implicated in long-term metabolic derangements in the offspring in the form of obesity/overweight, hypertension, dysglycemia, insulin resistance, and dyslipidemias later in life. To determine the prevalence of anthropometric and metabolic derangements in children between 1 and 5 years of age, born to women with GDM. Methods: This hospital-based cross-sectional study was conducted between November 2019 and November 2021 at our Pediatric Endocrine Clinic. Women were diagnosed as having GDM based on the American Diabetes Association Criteria (2019). History regarding the treatment of the GDM (diet only/diet and medical treatment) and detailed physical examination, including anthropometry and blood pressure, were recorded. Blood samples were collected from children for the estimation of their metabolic profile. Results: Overweight, obesity, and severe obesity were present in 18 (11.3%), 2 (1.3%), and 2 (1.3%) children, respectively. Hypertension was found in 21 (19.4%) children. Elevated LDL, triglyceride, and total cholesterol were seen in 3 (1.9%), 84 (52.5%), and 1 (0.6%) children, respectively. Impaired fasting glucose (IFG) was found in 6 (3.8%) children, while 27 (16.9%) subjects were found to be having impaired glucose tolerance after OGTT. Insulin resistance was found in 30 (18.8%) children. GDM mothers with a higher BMI tended to have children with a higher BMI (correlation coefficient, r = .414, P < .001). Higher serum triglyceride levels (r = -0.034, P = 0.672) were recorded in children, irrespective of the BMI of their mothers. There was no significant correlation of maternal BMI with blood pressure (r = -0.134, P = 0.091) or with HOMA-IR (r = 0.00, P = 0.996) in children. However, mothers with a higher BMI had children with statistically higher fasting blood glucose (r = +0.339, P = <0.001) as well as blood glucose 2 hours after OGTT (r = +0.297, P = <0.001). This positive correlation of maternal BMI with the glucose metabolism of their offspring was observed for both male and female genders. Conclusion: Children of women with GDM had a higher BMI, and the mode of treatment for GDM did not lead to differences in childhood BMI. The higher BMI of a GDM mother is associated with altered glucose metabolism in their offspring. Deranged levels of triglyceride across the gender were not found to be statistically significant. This has implications for future metabolic and cardiovascular risks in targeting this group for intervention studies to prevent obesity and disorders of glucose metabolism as one potential strategy to prevent adverse metabolic health outcomes.

Variations in Mating and Reproduction in Oriental Fruit Moth Caused by Adult Physiological State in Laboratory Tests.

Grapholita molesta (Busck) is a pest of rosaceous fruit plants worldwide. Due to a combination of monandry and promiscuity in G. molesta, the age and mating history of both sexes significantly affected the mating and reproductive success. In this study, the interactions of different ages (3, 5, or 7 days) and mating history (unmated or mated) in each sex on the mating selection, reproductive system, and offspring production were investigated in the laboratory. The results showed that these differences mainly occurred in young females or males, associated with unmated or mated state. Especially, the 3-day-old unmated females were preferred by the 7-day-old males but discriminated against by the 3- or 5-day-old unmated males, whereas the 3-day-old mated males were preferred by the 3-day-old mated or 7-day-old females but discriminated against by the 3- or 5-day-old unmated females. The lengths of the ovarian ducts were affected by age in the unmated females, with the greatest length being found at 7 days old. The size of testes varied with age in the unmated males, being the largest at 3 days old. At 3 days old, the testes size of the unmated males was larger than that of the mated males. The pairing of 5-day-old unmated females × 3-day-old mated males maximized the successful matings. The least productive pairing was 7-day-old unmated females × 5-day-old mated males. The pairing of 5-day-old mated males × 3-day-old mated females had the lowest number of matings and the highest number of offspring. The pairing of 3-day-old mated females × 3-day-old mated males had a high rate of mating success and the most offspring. These results revealed the different roles between females and males because of physiological states in terms of the reproductive biology in G. molesta.

Up-regulation of BRD4 contributes to gestational diabetes mellitus-induced cardiac hypertrophy in offspring by promoting mitochondria dysfunction in sex-independent manner.

Gestational diabetes mellitus (GDM) is associated with cardiovascular disease in postnatal life. The current study tested the hypothesis that GDM caused the cardiac hypertrophy in fetal (ED18.5), postnatal day 7 (PD7), postnatal day 21 (PD21) and postnatal day 90 (PD90) offspring by upregulation of BRD4 and mitochondrial dysfunction. Pregnant mice were divided into control and GDM groups. Hearts were isolated from ED18.5, PD7, PD21 and PD90. GDM increased the body weight (BW) and heart weight (HW) in ED18.5 and PD7, but not PD21 and PD90 offspring. However, HW/BW ratio was increased in all ages of GDM offspring compared to control group. Electron microscopy showed disorganized myofibrils, mitochondrial swelling, vacuolization, and cristae disorder in GDM offspring. GDM resulted in myocardial hypertrophy in offspring, which persisted from fetus to adult in a sex-independent manner. Echocardiography analysis revealed that GDM caused diastolic dysfunction, but had no effect on systolic function. Meanwhile, myocardial BRD4 was significantly upregulated in GDM offspring and BRD4 inhibition by JQ1 alleviated GDM-induced myocardial hypertrophy in offspring. Co-immunoprecipitation showed that BRD4 interacted with DRP1 and there was an increase of BRD4 and DRP1 interaction in GDM offspring. Furthermore, GDM caused the accumulation of damaged mitochondria in hearts from all ages of offspring, including mitochondrial fusion fission imbalance (upregulation of DRP1, and downregulation of MFN1, MFN2 and OPA1) and myocardial mitochondrial ROS accumulation, which was reversed by JQ1. These results suggested that the upregulation of BRD4 is involved in GDM-induced myocardial hypertrophy in the offspring through promoting mitochondrial damage in a gender-independent manner.

In utero chronic intermittent nicotine aerosol exposure increases ischemic heart injury in adult offspring via programming of Angiotensin II receptor-derived TGFß/ROS/Akt signaling pathway.

BACKGROUND: In utero cigarette smoking/nicotine exposure during pregnancy significantly affects fetal development and increases the risk of cardiovascular disease late in life. However, the underlying molecular mechanisms remain largely unknown. We tested the hypothesis that fetal nicotine aerosol exposure reprograms ischemia-sensitive gene expressions, resulting in increased heart susceptibility to ischemic injury and cardiac dysfunction in adulthood. METHODS: Pregnant rats were exposed to chronic intermittent nicotine aerosol (CINA) or saline aerosol control from gestational day 4 to day 21. Experiments were performed on 6-month-old adult offspring. RESULTS: CINA exposure increased ischemia-induced cardiac injury and cardiac dysfunction compared to the control group, which was associated with over- expression of angiotensin II receptor (ATR) protein in the left ventricle (LV) of adult offspring. Meanwhile, CINA exposure up-regulated cardiac TGF-ß/SMADs family proteins in the LV. In addition, CINA exposure enhanced cardiac reactive oxygen species (ROS) production and increased the DNA methylation level. The levels of phosphorylated-Akt were upregulated but LC3B-II/I protein abundances were downregulated in the hearts isolated from the CINA-treated group. CONCLUSION: Fetal nicotine aerosol exposure leads to cardiac dysfunction in response to ischemic stimulation in adulthood. Two molecular pathways are implicated. First, fetal CINA exposure elevates cardiac ATR levels, affecting the TGFß-SMADs pathway. Second, heightened Angiotensin II/ATR signaling triggers ROS production, leading to DNA hypermethylation, p-Akt activation, and autophagy deficiency. These molecular shifts in cardiomyocytes result in the development of a heart ischemia-sensitive phenotype and subsequent dysfunction in adult offspring.

Brain region-specific alterations in gene expression trajectories in the offspring born from influenza A virus infected mice.

Influenza A virus (IAV) infection during pregnancy can increase the risk for neurodevelopmental disorders in the offspring, however, the underlying neurobiological mechanisms are largely unknown. To recapitulate viral infection, preclinical studies have traditionally focused on using synthetic viral mimetics, rather than live IAV, to examine consequences of maternal immune activation (MIA)-dependent processes on offspring. In contrast, few studies have used live IAV to assess effects on global gene expression, and none to date have addressed whether moderate IAV, mimicking seasonal influenza disease, alters normal gene expression trajectories in different brain regions across different stages of development. Herein, we show that moderate IAV infection during pregnancy, which causes mild maternal disease and no overt foetal complications in utero, induces lasting effects on the offspring into adulthood. We observed behavioural changes in adult offspring, including disrupted prepulse inhibition, dopaminergic hyper-responsiveness, and spatial recognition memory deficits. Gene profiling in the offspring brain from neonate to adolescence revealed persistent alterations to normal gene expression trajectories in the prefronal cortex, hippocampus, hypothalamus and cerebellum. Alterations were found in genes involved in inflammation and neurogenesis, which were predominately dysregulated in neonatal and early adolescent offspring. Notably, late adolescent offspring born from IAV infected mice displayed altered microglial morphology in the hippocampus. In conclusion, we show that moderate IAV during pregnancy perturbs neurodevelopmental trajectories in the offspring, including alterations in the neuroinflammatory gene expression profile and microglial number and morphology in the hippocampus, resulting in behavioural changes in adult offspring. Such early perturbations may underlie the vulnerability in human offspring for the later development of neurodevelopmental disorders, including schizophrenia. Our work highlights the importance of using live IAV in developing novel preclinical models that better recapitulate the real-world impact of inflammatory insults during pregnancy on offspring neurodevelopmental trajectories and disease susceptibility later in life.

Leucocytozoon Infection Does Not Influence the Survival of Boreal Owl Aegolius funereus Nestlings.

Leucocytozoon infection has been observed to impact the reproductive ecology and physiology of avian hosts, but its influence on nestling survival remains unclear. We investigated the effect of Leucocytozoon infection intensity, determined through triplicate PCR sample analyses, on the survival of 256 boreal owl (Aegolius funereus) nestlings during an 8-yr study. Contrary to our expectations, the survival probability of boreal owl nestlings was not influenced by their Leucocytozoon infection intensity. Nestling age and Leucocytozoon infection intensity in male and female parents also did not impact nestling survival. Instead, food abundance and hatching order were the key factors influencing nestling survival. Additionally, we observed a significantly higher Leucocytozoon infection intensity in male parents compared to female parents and nestlings. We suggest a distinct division of parental roles may lead females and nestlings staying within the nest boxes (cavities) to experience lower exposure to potential vectors transmitting blood parasites than their male counterparts. Our study shows that Leucocytozoon disease may not be lethal for boreal owl chicks, exhibiting a below-average infection intensity compared to their male parents.

La infección por Leucocytozoon no influye en la supervivencia de los polluelos de mochuelo boreal Aegolius funereus. Se ha observado que la infección por Leucocytozoon afecta la ecología y fisiología reproductiva de las aves hospedadoras, pero su influencia en la supervivencia de los polluelos aún no está completamente determinada. Se investigó el efecto de la intensidad de la infección por Leucocytozoon, determinada mediante análisis de muestras de PCR por triplicado, sobre la supervivencia de 256 polluelos de mochuelo boreal (Aegolius funereus) durante un estudio de ocho años. Contrariamente a nuestras expectativas, la probabilidad de supervivencia de los polluelos de mochuelo boreal no se vio influenciada por la intensidad de la infección por Leucocytozoon. La edad de los polluelos y la intensidad de la infección por Leucocytozoon en los padres machos y hembras tampoco afectaron la supervivencia de los polluelos. En cambio, la abundancia de alimento y el orden de eclosión fueron los principales factores que influyeron en la supervivencia de los polluelos. Además, se observó una intensidad de infección por Leucocytozoon significativamente mayor en los padres machos en comparación con las hembras y los polluelos. Se sugiere que una clara división de los roles parentales puede llevar a que las hembras y los polluelos que permanecen dentro de las cajas nido (cavidades) experimenten una menor exposición a vectores potenciales que transmitan parásitos sanguíneos en comparación con los individuos adultos masculinos. Nuestro estudio muestra que la enfermedad de Leucocytozoon puede no ser letal para los polluelos de mochuelo boreal, ya que exhiben una intensidad de infección por debajo del promedio en comparación con sus padres machos.