Maternal Offspring Research Articles

Maternal-Infant Factors in Relation to Extracellular Vesicle and Particle miRNA in Prenatal Plasma and in Postpartum Human Milk.

MicroRNAs (miRNA) in extracellular vesicles and particles (EVPs) in maternal circulation during pregnancy and in human milk postpartum are hypothesized to facilitate maternal-offspring communication via epigenetic regulation. However, factors influencing maternal EVP miRNA profiles during these two critical developmental windows remain largely unknown. In a pilot study of 54 mother-child dyads in the New Hampshire Birth Cohort Study, we profiled 798 EVP miRNAs, using the NanoString nCounter platform, in paired maternal second-trimester plasma and mature (6-week) milk samples. In adjusted models, total EVP miRNA counts were lower for plasma samples collected in the afternoon compared with the morning (p = 0.024). Infant age at sample collection was inversely associated with total miRNA counts in human milk EVPs (p = 0.040). Milk EVP miRNA counts were also lower among participants who were multiparous after delivery (p = 0.047), had a pre-pregnancy BMI > 25 kg/m2 (p = 0.037), or delivered their baby via cesarean section (p = 0.021). In post hoc analyses, we also identified 22 specific EVP miRNA that were lower among participants who delivered their baby via cesarean section (Q < 0.05). Target genes of delivery mode-associated miRNAs were over-represented in pathways related to satiety signaling in infants (e.g., CCKR signaling) and mammary gland development and lactation (e.g., FGF signaling, EGF receptor signaling). In conclusion, we identified several key factors that may influence maternal EVP miRNA composition during two critical developmental windows, which should be considered in future studies investigating EVP miRNA roles in maternal and child health.

Mitochondrial Deoxyribonucleic Acid (mtDNA), Maternal Inheritance, and Their Role in the Development of Cancers: A Scoping Review.

Mitochondrial DNA (mtDNA) is a small, circular, double-stranded DNA inherited from the mother during fertilization. Evolutionary evidence supported by the endosymbiotic theory identifies mitochondria as an organelle that could have descended from prokaryotes. This may be the reason for the independent function and inheritance pattern shown by mtDNA. The unstable nature of mtDNA due to the lack of protective histones, and effective repair systems make it more vulnerable to mutations. The mtDNA and its mutations could be maternally inherited thereby predisposing the offspringto various cancers like breast and ovarian cancers among others.Although mitochondriaare considered heteroplasmic wherein variations among the multiple mtDNA genomes are noticed, mothers can have mitochondrial populations that are homoplasmic for a given mitochondrial mutation.Homoplasmic mitochondrial mutations may be transmitted to all maternal offspring. However, due to the complex interplay between the mitochondrial and nuclear genomes, it is often difficult to predict disease outcomes, even with homoplasmic mitochondrial populations.Heteroplasmic mtDNA mutations can be maternally inherited, but the proportion of mutated alleles differs markedly between offspring within one generation. This led to the genetic bottleneck hypothesis, explaining the rapid changes in allele frequency witnessed during the transmission of mtDNA from one generation to the next. Although a physical reduction in mtDNA has been demonstrated in several species, a comprehensive understanding of the molecular mechanisms is yet to be demonstrated. Despite initially thought to be limited to the germline, there is evidence that blockages exist in different cell types during development, perhaps explaining why different tissues in the same organism contain different levels of mutated mtDNA. In this review, we comprehensively discuss the potential mechanisms through which mtDNA undergoes mutationsand the maternal mode of transmissionthat contributes to the development of tumors, especially breast and ovarian cancers.

The impact of the microbes on puppies and kittens microbiota: a review

Recently it was discovered that canine and feline neonates are not born in a sterile environment as was stated previously. The acquisition, colonization, and maintenance of early life microbiota is a rapidly developing area of research. In humans it has been seen that the infant microbiome plays an essential role in human health and its composition is determined by maternal–offspring exchanges of microbiota. Even though this topic is becoming more and more important in dogs and cats, the exact role of the neonatal microbiome is not yet known. In this review, the current knowledge about the neonatal microbiome in puppies and kittens is summarized.

The fascinating microbes and their impact on neonatal dogs and cats - A review.

Recent literature data indicate that canine and feline neonates are not born in a sterile environment as it was stated previously. The acquisition, colonisation and maintenance of the early life microbiota of healthy fetuses is a rapidly developing research area. In humans, the natural healthy infant microbiome plays an essential role in health and its assembly is determined by the maternal-offspring exchanges of microbes. Even though this topic is becoming more and more important in dogs and cats, the exact role of the neonatal microbiome is not yet fully known in animals. This review summarises the current knowledge of the normal physiological neonatal microbiome in healthy puppies and kittens.

Abstracts from the NIH Office of Research on Women's Health 2022 Annual BIRCWH Meeting:Building Interdisciplinary Research Careers in Women's Health November 2, 2022

Abstracts from the NIH Office of Research on Women's Health 2022 Annual BIRCWH Meeting:Building Interdisciplinary Research Careers in Women's Health November 2, 2022

Abstract 3652: Maternal body mass index, diabetes, and gestational weight gain and risk for pediatric cancer in offspring: A systematic review and meta-analysis

Abstract Introduction: Pediatric cancer incidence has steadily increased concurrent with the rise in adult obesity, however, associations between maternal obesity and associated comorbidities and pediatric cancer risk remain understudied. Methods: A comprehensive and systematic literature search in PubMed and EMBASE databases from their inception to March 15th, 2021. Eligible studies reported risk estimates, sample sizes, and provided sufficient description of outcome and exposure ascertainment. Studies were excluded if not complete, published, peer-reviewed studies, or if provided incompatible exposure data. Data quality was assessed according to Newcastle-Ottawa Scale (NOS) guidelines and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Random-effects models were used to estimate pooled effects. Results: Thirty-four studies were included, covering 3,404,747 subjects and 14,706 pediatric cancer cases for pre-pregnancy BMI; 14,748,772 subjects and 44,628 pediatric cancer patients for maternal diabetes; and 2,124,647 participants and 15,915 pediatric cancer cases for gestational weight gain. Pre-pregnancy BMI was significantly associated with leukemia risk in offspring (OR per 5-unit BMI increase =1.07 [95% CI = 1.04-1.11] I2 = 0.0%). Any maternal diabetes was positively associated with acute lymphoblastic leukemia risk (OR=1.46 [95% CI = 1.28-1.67] I2 = 0.0%), even after restricting to birthweight-adjusted analyses (OR [95% CI] = 1.74 [1.29-2.34] I2 = 0.0%), and inversely associated with risk of central nervous system tumors (OR=0.73 [95% CI = 0.55-0.97] I2 = 0.0%). Pre-gestational diabetes (OR=1.57 [95% CI = 1.11-2.24] I2 = 26.8%) and gestational diabetes (OR=1.40 [95% CI = 1.12-1.75] I2 = 0.0%) were also significantly associated with acute lymphoblastic leukemia risk. No significant associations were observed for gestational weight gain and pediatric cancer risk. Conclusions: Maternal obesity and diabetes may be etiologically linked to pediatric cancer, particularly leukemia and central nervous system tumors. Our findings support appropriate weight management and glycemic control as important components of maternal care and offspring health. Further validation studies are warranted. Citation Format: Andrew R. Marley, Allison Domingues, Taumoha Ghosh, Lucie M. Turcotte, Logan G. Spector. Maternal body mass index, diabetes, and gestational weight gain and risk for pediatric cancer in offspring: A systematic review and meta-analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3652.

Network Approaches to Integrate Analyses of Genetics and Metabolomics Data with Applications to Fetal Programming Studies

The integration of genetics and metabolomics data demands careful accounting of complex dependencies, particularly when modelling familial omics data, e.g., to study fetal programming of related maternal–offspring phenotypes. Efforts to identify genetically determined metabotypes using classic genome wide association approaches have proven useful for characterizing complex disease, but conclusions are often limited to a series of variant–metabolite associations. We adapt Bayesian network models to integrate metabotypes with maternal–offspring genetic dependencies and metabolic profile correlations in order to investigate mechanisms underlying maternal–offspring phenotypic associations. Using data from the multiethnic Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study, we demonstrate that the strategic specification of ordered dependencies, pre-filtering of candidate metabotypes, incorporation of metabolite dependencies, and penalized network estimation methods clarify potential mechanisms for fetal programming of newborn adiposity and metabolic outcomes. The exploration of Bayesian network growth over a range of penalty parameters, coupled with interactive plotting, facilitate the interpretation of network edges. These methods are broadly applicable to integration of diverse omics data for related individuals.

The mediating effect of DNA methylation in the association between maternal sleep during pregnancy and offspring adiposity status: a prospective cohort study

BackgroundChildhood overweight/obesity is a global public health concern. It is important to identify its early-life risk factors. Maternal poor sleep is common in late pregnancy, and previous studies indicated that poor sleep may influence the offspring’s adiposity status. However, very few studies in humans investigated the effect of the different sleep parameters (sleep quantity, quality, and timing) on the offspring’s adiposity indicators, and long-term studies are even more scarce. In addition, the underlying mechanism remains unclear. The present study therefore aimed to examine the association between the three maternal sleep dimensions in the late pregnancy and the offspring adiposity indicators and to explore the potential mediating effect of the cord blood DNA methylation in the above association.MethodsIncluded participants in the current study were 2211 healthy pregnant women with singleton gestation from the Shanghai Birth Cohort (SBC) and Shanghai Sleep Birth Cohort (SSBC). Maternal nighttime sleep duration, quality, and midpoint (an indicator of circadian rhythm) were assessed by the same instrument in both cohorts during late pregnancy, and the offspring’s body mass index (BMI) and subcutaneous fat (SF) were measured at 2 years old. Additionally, in 231 SSBC samples, the genome-wide DNA methylation levels were measured using the Illumina Infinium Methylation EPIC BeadChip. The multivariate linear regression was used to determine the associations between the maternal sleep parameters and the offspring adiposity indicators. The epigenome-wide association study was conducted to identify the maternal sleep-related CpG sites. The mediation analysis was performed to evaluate the potential intermediate role of DNA methylation in the association between maternal sleep and offspring adiposity indicators.ResultsThe mean maternal nighttime sleep duration and the sleep midpoint for combined cohorts were 9.24 ± 1.13 h and 3.02 ± 0.82, respectively, and 24.5% of pregnant women experienced poor sleep quality in late pregnancy. After adjusting for the covariates, the maternal later sleep midpoint was associated with the increased SF in offspring (Coef. = 0.62, 95% CI 0.37–0.87, p < 0.001) at 2 years old. However, no significant associations of the nighttime sleep duration or sleep quality with the offspring adiposity indicators were found. In the SSBC sample, 45 differential methylated probes (DMPs) were associated with the maternal sleep midpoint, and then, we observed 10 and 3 DMPs that were also associated with the offspring’s SF and BMI at 2 years, of which cg04351668 (MARCH9) and cg12232388 significantly mediated the relationship of sleep midpoint and SF and cg12232388 and cg12225226 mediated the sleep midpoint–BMI association, respectively.ConclusionsMaternal later sleep timing in late pregnancy was associated with higher childhood adiposity in the offspring. Cord blood DNA methylation may play a mediation role in that relationship.

Maternal iron status in early pregnancy and DNA methylation in offspring: an epigenome-wide meta-analysis

BackgroundUnbalanced iron homeostasis in pregnancy is associated with an increased risk of adverse birth and childhood health outcomes. DNA methylation has been suggested as a potential underlying mechanism linking environmental exposures such as micronutrient status during pregnancy with offspring health. We performed a meta-analysis on the association of maternal early-pregnancy serum ferritin concentrations, as a marker of body iron stores, and cord blood DNA methylation. We included 1286 mother–newborn pairs from two population-based prospective cohorts. Serum ferritin concentrations were measured in early pregnancy. DNA methylation was measured with the Infinium HumanMethylation450 BeadChip (Illumina). We examined epigenome-wide associations of maternal early-pregnancy serum ferritin and cord blood DNA methylation using robust linear regression analyses, with adjustment for confounders and performed fixed-effects meta-analyses. We additionally examined whether associations of any CpGs identified in cord blood persisted in the peripheral blood of older children and explored associations with other markers of maternal iron status. We also examined whether similar findings were present in the association of cord blood serum ferritin concentrations with cord blood DNA methylation.ResultsMaternal early-pregnancy serum ferritin concentrations were inversely associated with DNA methylation at two CpGs (cg02806645 and cg06322988) in PRR23A and one CpG (cg04468817) in PRSS22. Associations at two of these CpG sites persisted at each of the follow-up time points in childhood. Cord blood serum ferritin concentrations were not associated with cord blood DNA methylation levels at the three identified CpGs.ConclusionMaternal early-pregnancy serum ferritin concentrations were associated with lower cord blood DNA methylation levels at three CpGs and these associations partly persisted in older children. Further studies are needed to uncover the role of these CpGs in the underlying mechanisms of the associations of maternal iron status and offspring health outcomes.

MO078: Dietary Supplementation with Cysteine During Pregnancy Rescues Maternal Chronic Kidney Disease-Induced Hypertension in Male Rat Offspring: The Impact of Hydrogen Sulphide and Microbiota-Derived Tryptophan Metabolites

Abstract BACKGROUND AND AIMS Maternal chronic kidney disease (CKD) is linked to offspring hypertension. Gut microbiome and its tryptophan metabolites, nitric oxide (NO) and renin–angiotensin system (RAS) are closely related to the development of hypertension. Hydrogen sulphide (H2S) has shown antihypertensive effect. Our objective was to test whether L- or D-cysteine supplementation in pregnancy can prevent hypertension programmed by maternal CKD in adult offspring and explored the protective mechanisms. METHOD CKD was induced in pregnant Sprague-Dawley rats by a 0.5% adenine diet for 3 weeks. L- or D-cysteine was supplemented at 8 mmol/kg body weight/day during pregnancy. Male offspring were sacrificed at the age of 12 weeks (n = 8/group). RESULTS Maternal CKD-induced hypertension was similarly prevented by L- or D-cysteine supplementation. The protective effects of L- and D-cysteine are related to reducing oxidative stress, rebalancing the RAS and reshaping the gut microbiome. L-cysteine therapy protected adult offspring against hypertension and was associated with enhanced H2S production, restoration of NO bioavailability, enhancement of beneficial genera Oscillibacter and Butyricicoccus, depletion of indole-producing genera Alistipes and Akkermansia and reduction of indole metabolites. D-cysteine treatment increased tryptophan metabolites in the kynurenine pathway, decreased those in the serotonin pathway and enriched the genera Bacteroides and Odoribacter abundance. CONCLUSION In summary, these results suggest that L- and D-cysteine protect against maternal CKD-induced offspring hypertension, likely by enhancing H2S production, modulating gut microbiota and its derived metabolites and restorating NO and RAS.

S10.3: Transmission of stress signals: The maternal microbiome and offspring health

S10.3: Transmission of stress signals: The maternal microbiome and offspring health

Factors influencing ease of whelping and its relationship with maternal behaviour and puppy perinatal mortality in commercially bred dogs

For dog breeders, parturition is a critical stage in the reproductive cycle of the dam. Evidence in other mammals suggests that a difficult labour can influence maternal behaviour and offspring viability during the first hours postpartum. However, the effect of whelping difficulty on the onset of maternal behaviour has not yet been investigated in domestic dogs. Here we developed an ease of whelping (EoW) index in dams maintained within a Commercial dog Breeding Establishment (CBE) environment and investigated the relationship between intrinsic and extrinsic factors (breed group according to size/weight, litter size, parity, whelping season and origin of the dam), EoW, early maternal behaviour and puppy perinatal mortality. The behaviour of 30 dams was observed throughout the whelping process, starting 24 h before delivery of the first puppy until birth of the last puppy. Parturition duration, birth interval, and behaviours indicative of distress, restlessness, and general activity were scored and included in a Principal Component Analysis to construct the EoW index. Subsequently, mother–pup interactions and puppy perinatal mortality were recorded during the first 24 and 72 h postpartum respectively. Results showed that EoW was significantly affected by whelping season, litter size and origin of the dam (whether she was born and raised within the CBE or brought in). Furthermore, mothers that experienced more difficult parturitions (higher EoW score) spent more time lying in contact with their puppies during the first 24 h postpartum. Time in contact with puppies was also significantly affected by breed group. Nursing duration was significantly affected by breed group and origin of the dam. Additionally, medium-size breed (10–20 kg) puppies were significantly less likely to experience perinatal mortality than large breeds (> 20 kg). These findings are particularly relevant for the welfare of breeding dams maintained in large-scale CBEs where the staff-to-dog ratio might be insufficient to adequately manage multiple simultaneous parturitions.

Effects of the Leptin-Mediated MAPK/ERK Signaling Pathway on Collagen II Expression in Knee Cartilage of Newborn Male Mice from Obese Maternal Offspring.

Epidemiological data suggest that various noncommunicable diseases develop as a result of altered maternal metabolic and physiological status due to exposure to several adverse factors during pregnancy. However, evidence for intrauterine exposure factors and mechanisms underlying the origin of early cartilage disease in chronic osteoarthritic disease is still lacking. In this study, we found that persistent overnutrition during pregnancy in obese mothers led to cartilage damage in neonatal male mice. This was mainly characterized by increased apoptosis with decreased expression of chondrocyte collagen II and low expression of Runx family transcription factor 2 (RUNX2) and SRY-box transcription factor 9 (SOX9). This reduction was also found to be associated with high leptin expression in newborn male mice of obese maternal offspring. Furthermore, the administration of leptin and mitogen-activated protein kinase (MAPK)-extracellular signal-regulated kinase (ERK) inhibitors in primary chondrocytes showed that leptin mediated MAPK/ERK signaling activation and thus affected the key regulators of cartilage matrix metallopeptidase 1 (MMP1) and tissue inhibitor of metalloproteinase 1 (TIMP1), thereby altering the expression of collagen II in mouse cartilage. Altogether, this study provided insights into the molecular mechanisms of cartilage-related disease development and also new clues and evidence for the fetogenetic origin of cartilage diseases.

Cumulative Metabolic and Epigenetic Effects of Paternal and/or Maternal Supplementation with Arachidonic Acid across Three Consecutive Generations in Mice.

Apart from the known associations between arachidonic acid (AA), weight gain, and neurological and immune function, AA exposure leads to alterations in global and gene-specific DNA methylation (DNAm) and fatty acid (FA) content in human cultured cells. However, it is unknown as to whether the latter effects occur in vivo and are maintained over extended periods of time and across generations. To address this issue, we asked whether AA supplementation for three consecutive generations (prior to coitus in sires or in utero in dams) affected offspring growth phenotypes, in addition to liver DNAm and FA profiles in mice. Twelve-week-old BALB/c mice were exposed daily to AA dissolved in soybean oil (vehicle, VH), or VH only, for 10 days prior to mating or during the entire pregnancy (20 days). On average, 15 mice were supplemented per generation, followed by analysis of offspring body weight and liver traits (x average = 36 and 10 per generation, respectively). Body weight cumulatively increased in F2 and F3 offspring generations and positively correlated with milligrams of paternal or maternal offspring AA exposure. A concomitant increase in liver weight was observed. Notably, akin to AA-challenged cultured cells, global DNAm and cis-7-hexadecenoic acid (16:1n-9), an anti-inflammatory FA that is dependent on stearoyl-CoA desaturase 1 (SCD1) activity, increased with milligrams of AA exposure. In accordance, liver Scd1 promoter methylation decreased with milligrams of germline AA exposure and was negatively correlated with liver weight. Our results show that mice retain cellular memories of AA exposure across generations that could potentially be beneficial to the innate immune system.

Maternal age and maternal environment affect egg composition, yolk testosterone, offspring growth and behaviour in laying hens

Maternal effects have been reported to alter offspring phenotype in laying hens. In this study, we investigated the effects of maternal environment and maternal age on egg traits and offspring development and behaviour. For this, we ran two experiments. First (E1), commercial hybrid hens were reared either in aviary or barren brooding cages, then housed in aviary, conventional cages or furnished (enriched) cages, thus forming different maternal housing treatments. Hens from each treatment were inseminated at three ages, and measures of egg composition, yolk testosterone concentration and offspring’s development, anxiety and fearfulness were assessed. In experiment 2 (E2), maternal age effects on offspring's growth and behaviour were further investigated using fertile eggs from commercial breeder flocks at three different ages. Results from E1 showed that Old hens laid heavier eggs with less yolk testosterone and produced offspring with fewer indicators of anxiety and fearfulness. Maternal rearing and housing affected egg traits, offspring weight and behaviour, but not in a consistent way. Effects of maternal age were not replicated in E2, possibly due to differences in management or higher tolerance to maternal effects in commercial breeders. Overall, our research confirms that maternal age and maternal environment affects egg composition, with maternal age specifically affecting yolk testosterone concentration, which may mediate physical and behavioural effects in offspring.

Association of MTHFD1 gene polymorphisms and maternal smoking with risk of congenital heart disease: a hospital-based case-control study

BackgroundMTHFD1 gene may affect the embryonic development by elevated homocysteine levels, DNA synthesis and DNA methylation, but limited number of genetic variants of MTHFD1 gene was focused on the association with congenital heart disease (CHD). This study examined the role of MTHFD1 gene and maternal smoking on infant CHD risk, and investigated their interaction effects in Chinese populations.MethodsA case-control study of 464 mothers of CHD infants and 504 mothers of health controls was performed. The exposures of interest were maternal tobacco exposure, single nucleotide polymorphisms (SNPs) of maternal MTHFD1 gene. The logistic regression model was used for accessing the strength of association.ResultsMothers exposed to secondhand smoke during 3 months before pregnancy (adjusted odds ratio [aOR] = 1.56; 95% confidence interval [CI]: 1.13–2.15) and in the first trimester of pregnancy (aOR = 2.24; 95%CI: 1.57–3.20) were observed an increased risk of CHD. Our study also found that polymorphisms of maternal MTHFD1 gene at rs1950902 (AA vs. GG: aOR = 1.73, 95% CI: 1.01–2.97), rs2236222 (GG vs. AA: aOR = 2.38, 95% CI: 1.38–4.12), rs1256142 (GA vs.GG: aOR = 1.57, 95% CI: 1.01–2.45) and rs11849530 (GG vs. AA: aOR = 1.68, 95% CI: 1.02–2.77) were significantly associated with higher risk of CHD. However, we did not observe a significant association between maternal MTHFD1 rs2236225 and offspring CHD risk. Furthermore, we found the different degrees of interaction effects between polymorphisms of the MTHFD1 gene including rs1950902, rs2236222, rs1256142, rs11849530 and rs2236225, and maternal tobacco exposure.ConclusionsMaternal polymorphisms of MTHFD1 gene, maternal tobacco exposure and their interactions are significantly associated with the risk of CHD in offspring in Han Chinese populations. However, more studies in different ethnic populations with a larger sample and prospective designs are required to confirm our findings.Trial registrationRegistration number: ChiCTR1800016635.

Childhood Blood Pressure, Carotid Intima Media Thickness, and Distensibility After In Utero Exposure to Gestational Hypertensive Disorders.

BackgroundOffspring exposed to gestational hypertensive disorders have higher blood pressure and increased risk of stroke in later life. Gestational hypertensive disorders might influence vascular development in the offspring, predisposing them to a higher blood pressure and stroke in later life.Methods and ResultsIn a population‐based cohort among 4777 mother–offspring pairs, we examined whether gestational hypertension, preeclampsia, and higher gestational blood pressure across the full blood pressure spectrum were associated with offspring blood pressure, carotid intima media thickness, and distensibility at the age of 10 years. Offspring exposed to gestational hypertension, but not preeclampsia, had higher systolic and diastolic blood pressure (0.17 [95% CI, 0.02–0.31] and 0.23 [95% CI, 0.08–0.38] increases in standard deviation scores, respectively), whereas no associations with intima media thickness and distensibility were present. Higher maternal systolic and diastolic blood pressure in early, mid, and late pregnancy were associated with higher offspring systolic and diastolic blood pressure and lower distensibility (P values <0.05), but not with intima media thickness. The associations were not explained by maternal, birth, or child factors. Paternal systolic and diastolic blood pressure were also associated with these offspring outcomes (P values <0.05), with a comparable strength as maternal–offspring associations.ConclusionsGestational hypertension and higher gestational blood pressure, even below the diagnostic threshold for gestational hypertensive disorders, are associated with higher offspring blood pressure and lower carotid distensibility. No associations were found for preeclampsia with offspring vascular outcomes. As maternal–offspring and paternal–offspring associations were comparable, these associations are more likely driven by genetic predisposition and shared lifestyle rather than by a direct intrauterine effect.

Maternal effects of climate warming and nitrogen deposition vary with home and introduced ranges

AbstractMaternal effects allow offspring to cope with rapidly changing environments. While the immediate effects of long‐term climate warming and nitrogen (N) deposition are well documented, their maternal effects have been little studied.We conducted a 6‐year maternal experiment withSolidago canadensis(Canadian goldenrod), native to North America (home range) and invasive in China (introduced range), and then performed two offspring experiments to address how maternal warming, maternal N‐addition and population source interacted to influence offspring performance.Maternal effects of warming and N‐addition on seed traits, leaf dry matter content and whole‐plant biomass were stronger inS. canadensisoffspring from China (introduced range) than in offspring from North America (home range). Matched maternal–offspring environments allowed offspring to perform better compared to mismatched environments; offspring grown under warming flowered and produced seeds within a growing season only when their maternal plants were previously exposed to warming. Offspring environments influenced its performance and also modulated maternal effects.We suggest that the maternal effects of simulated climate warming and N deposition could vary with home and introduced ranges. Our findings imply that maternal warming could advance the reproductive phenology of offspring.A freePlain Language Summarycan be found within the Supporting Information of this article.

Immune Cell and Adipose Gene Expression Reprogramming in Juvenile Monkeys Born to Health and Weight-Diverse Mothers

Over 93 million Americans are obese and 66 million suffer from metabolic disease. Roughly 40% of obese people do not have metabolic abnormalities (metabolically health obese [MHO]), while approximately 15% of lean do (metabolically unhealthy lean [MUL]). African green monkeys (AGMs) demonstrate naturally occurring obesity and metabolic syndrome (MetS) without diet manipulation, and MetS criteria are heritable. Age-matched maternal AGMs were classified by adjusted MetS criteria ([n=44]; waist >40cm, fasting glucose (FG) >100 mg/dL, SBP/DBP >135/85mmHg, and HDL-c <50mg/dL) and classified as metabolically healthy lean (MHL), MHO, MUL or metabolically unhealthy obese (MUO). Age, weight and sex-matched pre-pubertal juvenile offspring from these mothers were additionally selected (n=9-11/group; ages=1.1-3.4years) for evaluation. We assessed monocyte subtypes by flow cytometry, and subcutaneous adipose gene expression patterns by RNAseq. Non-classical monocytes were increased in obese and unhealthy mothers (MHO p=0.02, MUL p=0.003, MUO p=0.00002) compared to MHL. MUL and MUO juvenile offspring also had more non-classical monocytes compared to MHL (p=0.05 and p=0.07). Monocyte chemoattractant protein-1 (MCP)-1 was measured in plasma and found to be elevated in MUO juveniles (p=0.02). Patterns of increased cytokine and extracellular matrix gene expression were seen in MUL and MUO juveniles’ adipose (6-7/group), mirroring obese and unhealthy mothers’ adipose gene expression patterns. Maternal health and obesity influence offspring immune cells and adipose gene expression prior to weight gain and metabolic disease onset. Our data underscore maternal monocyte and adipose profiles as inherited phenotypes that present prior to adipose expansion and may be targets to improve intergenerational health trajectories.

A Laboratory-Based Investigation of Links between Maternal Posttraumatic Stress Symptoms and Adolescent Offspring Anxiety

SYNOPSIS Objective . Maternal symptoms of posttraumatic stress are linked to problematic offspring outcomes, including internalizing problems, general behavioral problems, and altered psychobiological functioning. Maternal posttraumatic stress symptoms among trauma-exposed mothers as they relate to offspring functioning has not been evaluated, and laboratory-based affect elicitation procedures have not been used in this context. Design . Self-report of trauma-relevant symptoms in 40 mothers and their adolescents’ self-report indices of adolescent anxiety symptoms were obtained. Adolescents were also administered a laboratory-based induction of socially relevant anxious arousal, and maternal and adolescent anxiety in response to the task were recorded. Results . Maternal posttraumatic avoidance symptoms were associated with questionnaire- and laboratory-based indicators of adolescent anxiety. Conclusions . Maternal posttraumatic avoidance symptoms are associated with offspring anxiety; therefore, providers working with mothers with posttraumatic avoidance should consider screening adolescent offspring for anxiety symptoms.