Preconception Exposure Research Articles

Associations of Preconception Exposure to Air Pollution and Greenness with Offspring Asthma and Hay Fever.

We investigated if greenness and air pollution exposure in parents’ childhood affect offspring asthma and hay fever, and if effects were mediated through parental asthma, pregnancy greenness/pollution exposure, and offspring exposure. We analysed 1106 parents with 1949 offspring (mean age 35 and 6) from the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) generation study. Mean particulate matter (PM2.5 and PM10), nitrogen dioxide (NO2), black carbon (BC), ozone (O3) (µg/m3) and greenness (normalized difference vegetation index (NDVI)) were calculated for parents 0–18 years old and offspring 0–10 years old, and were categorised in tertiles. We performed logistic regression and mediation analyses for two-pollutant models (clustered by family and centre, stratified by parental lines, and adjusted for grandparental asthma and education). Maternal medium PM2.5 and PM10 exposure was associated with higher offspring asthma risk (odds ratio (OR) 2.23, 95%CI 1.32–3.78, OR 2.27, 95%CI 1.36–3.80), and paternal high BC exposure with lower asthma risk (OR 0.31, 95%CI 0.11–0.87). Hay fever risk increased for offspring of fathers with medium O3 exposure (OR 4.15, 95%CI 1.28–13.50) and mothers with high PM10 exposure (OR 2.66, 95%CI 1.19–5.91). The effect of maternal PM10 exposure on offspring asthma was direct, while for hay fever, it was mediated through exposures in pregnancy and offspring’s own exposures. Paternal O3 exposure had a direct effect on offspring hay fever. To conclude, parental exposure to air pollution appears to influence the risk of asthma and allergies in future offspring.

Maternal preconception and first trimester exposure to PM10 and the risk of oral clefts in offspring: a population-based, case–control study

BackgroundCurrent literature describes limited and controversial evidence on the associations between maternal preconception and first trimester exposure to particulate matter with a diameter ≤10 µm (PM10) and the risk of...

Particle air pollution and gestational diabetes mellitus in Houston, Texas

BackgroundThere is mixed evidence implicating prenatal exposure to particulate matter <2.5 μm in aerodynamic diameter (PM2.5) in the risk of gestational diabetes mellitus (GDM) and only one study has examined exposure to PM2.5 constituents, which vary with location because of different emission sources. MethodsWe conducted a retrospective cohort study of singleton live births in Harris County, Texas from 2008 to 2013. With data from the Texas Commission on Environmental Quality (TCEQ), we spatially interpolated maternal exposures to total and speciated PM2.5, nitrogen dioxide (NO2) and ozone (O3) over the 12-week preconception period and trimesters 1 and 2. We estimated odds ratios (OR) and 95% confidence intervals (CI) for the association between pre-conception and pregnancy exposures to total and speciated PM2.5 and odds of GDM, adjusted for temperature and maternal covariates. We also evaluated confounding from NO2 and O3 exposures in multi-pollutant models. ResultsAn interquartile range (IQR) increase in total PM2.5 exposure was associated with elevated odds for developing GDM over the preconception (adjusted OR = 1.09, 95% CI: 1.06, 1.12), first trimester (OR = 1.13, 95% CI: 1.10, 1.17) and second trimester (OR = 1.13, 95% CI: 1.09, 1.17) periods. Effect estimates increased with adjustment for NO2 and O3. We observed modest increases in odds of GDM for IQR increases in first trimester ammonium ion PM2.5 (OR = 1.03, 95% CI: 1.00, 1.05) and sulfate PM2.5 (OR = 1.03, 95% CI: 1.00, 1.05) exposures, as well as preconception Cr PM2.5 exposures (OR = 1.05, 95% CI: 1.02, 1.07). ConclusionExposures to PM2.5, before and during pregnancy were associated with elevated odds of GDM. Mitigating air pollution exposures may reduce the risk of GDM and its long-term implications for maternal and child health.

Pre-conception exposure to THC fails to impact nicotine reward in adult offspring

Exposure to environmental stimuli in one generation can produce altered behavioral and neurobiological phenotypes in descendants. Recent work has shown that parental exposure to cannabinoids alters the rewarding properties of other abused drugs in the subsequent generation. However, whether preconception Δ9-tetrahydrocannabinol (THC) administration modifies the affective properties of nicotine in offspring is unknown. To address this question, male and female rats (F0) received THC (0 or 1.5 mg/kg) throughout the adolescent window and were bred on PND 65. In Experiment 1, adult F1-THC and F1-Veh progeny (males and females) underwent nicotine locomotor sensitization procedures during which nicotine (0 or 0.4 mg/kg) was administered every other day for five exposures, and locomotor activity was recorded on each exposure followed by a final nicotine challenge. There was no cross-generational effect of THC on nicotine locomotor sensitization, although acute exposure to nicotine produced greater activity in females relative to males independent of THC history. In Experiment 2, adult F1-THC and F1-Veh progeny (males and females) were implanted with jugular catheters and trained to self-administer nicotine (0.03 mg/kg/infusion). Following acquisition, all subjects were allowed to self-administer nicotine on a number of reinforcement schedules, e.g., FR2, FR5 and PR, followed by dose response and extinction procedures. Across all indices, F1-THC and F1-Veh subjects displayed similar IVSA of nicotine with no sex differences. The fact that there was no evidence of cross-generational effects of THC on nicotine suggests that such effects are drug-specific.

Parental occupational exposure pre- and post-conception and development of asthma in offspring.

BackgroundWhile direct effects of occupational exposures on an individual’s respiratory health are evident, a new paradigm is emerging on the possible effects of pre-conception occupational exposure on respiratory health in offspring. We aimed to study the association between parental occupational exposure starting before conception and asthma in their offspring (at 0–15 years of age).MethodsWe studied 3985 offspring participating in the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) generation study. Their mothers or fathers (n = 2931) previously participated in the European Community Respiratory Health Survey (ECRHS). Information was obtained from questionnaires on parental job history pre- and post-conception which was linked to an asthma-specific job-exposure matrix (JEM). We assessed the association between parental occupational exposure and offspring asthma, applying logistic regression models, clustered by family and adjusted for study centre, offspring sex, parental characteristics (age, asthma onset, place of upbringing, smoking) and grandparents’ level of education.ResultsParental occupational exposure to microorganisms, pesticides, allergens or reactive chemicals pre-conception or both pre- and post-conception was not related to offspring asthma; in general, subgroup analyses confirmed this result. However, maternal exposure both pre- and post-conception to allergens and reactive chemicals was associated with increased odds for early-onset asthma in offspring (0–3 years of age); odds ratio 1.70 (95% CI: 1.02–2.84) and 1.65 (95% CI: 0.98–2.77), respectively.ConclusionsThis study did not find evidence that parental occupational exposure, defined by an asthma JEM before conception only or during pre- and post-conception vs non-exposed, was associated with offspring asthma.

Parents' smoking onset before conception as related to body mass index and fat mass in adult offspring: Findings from the RHINESSA generation study.

Emerging evidence suggests that parents' preconception exposures may influence offspring health. We aimed to investigate maternal and paternal smoking onset in specific time windows in relation to offspring body mass index (BMI) and fat mass index (FMI). We investigated fathers (n = 2111) and mothers (n = 2569) aged 39-65 years, of the population based RHINE and ECRHS studies, and their offspring aged 18-49 years (n = 6487, mean age 29.6 years) who participated in the RHINESSA study. BMI was calculated from self-reported height and weight, and FMI was estimated from bioelectrical impedance measures in a subsample. Associations with parental smoking were analysed with generalized linear regression adjusting for parental education and clustering by study centre and family. Interactions between offspring sex were analysed, as was mediation by parental pack years, parental BMI, offspring smoking and offspring birthweight. Fathers' smoking onset before conception of the offspring (onset ≥15 years) was associated with higher BMI in the offspring when adult (β 0.551, 95%CI: 0.174-0.929, p = 0.004). Mothers' preconception and postnatal smoking onset was associated with higher offspring BMI (onset <15 years: β1.161, 95%CI 0.378-1.944; onset ≥15 years: β0.720, 95%CI 0.293-1.147; onset after offspring birth: β2.257, 95%CI 1.220-3.294). However, mediation analysis indicated that these effects were fully mediated by parents' postnatal pack years, and partially mediated by parents' BMI and offspring smoking. Regarding FMI, sons of smoking fathers also had higher fat mass (onset <15 years β1.604, 95%CI 0.269-2.939; onset ≥15 years β2.590, 95%CI 0.544-4.636; and onset after birth β2.736, 95%CI 0.621-4.851). There was no association between maternal smoking and offspring fat mass. We found that parents' smoking before conception was associated with higher BMI in offspring when they reached adulthood, but that these effects were mediated through parents' pack years, suggesting that cumulative smoking exposure during offspring's childhood may elicit long lasting effects on offspring BMI.

Abstract A03: Preconception paternal DDT exposure and programming of metabolic dysfunction and breast cancer in offspring

Abstract The pesticide dichlorodiphenyltrichloroethane or DDT was widely used in agriculture or to combat insect-borne diseases until the 1970s in the United States and the 1980s in Europe. It continues to be used in developing countries to combat malaria or illegally to protect crops. Because of its prolonged half-life, DDT is a persistent environmental pollutant that still can detected in the American population, particularly in minorities and recent immigrants. Epidemiologic studies have shown that early-life (in utero and early childhood) exposure to DDT is associated with a four-fold increase in breast cancer risk in women, and these findings are supported by animal studies. While maternal DDT exposure in pregnancy has been linked to breast cancer in offspring, the effects of paternal DDT exposure on their progeny’s breast cancer development have not been investigated. Environmental exposures can induce epigenetic changes in paternal sperm and affect the risk of disease in their offspring. Here, we evaluated the effects of preconception exposure to DDT on the male sperm epigenome and programming of offspring’s susceptibility to breast cancer, using a mouse model. Male mice were exposed to DDT (1.7mg/kg body weight) by oral gavage in the preconception window. DDT and control-vehicle (CO) males were then used for sperm collection or housed with female mice, with free access to a standard chow diet, for three days. Pregnancy onset was assessed by the presence of a vaginal plug. The weight and number of pups per litter were determined two days after birth. Pups were weaned at 21 days of age and fed a standard chow diet for the extent of the study. Offspring were weighed weekly and used to study metabolic parameters. Mammary tumors were induced by administration of 15mg of medroxyprogesterone to six-week-old female offspring, followed by oral administration of 1mg 7,12-dimethylbenz[a]anthracene once a week for 3 weeks. RNA extracted from sperm CO and DDT males was used for small RNA-seq analysis. Preconception exposure to DDT altered small noncoding RNAs (e.g., miRNAs and tRNAs) in paternal sperm. In line with that, offspring of DDT-exposed fathers had a significant decrease in birth and weaning weights compared to controls. Further, DDT offspring showed metabolic dysfunction. Compared to CO, female offspring of DDT fathers had significantly accelerated breast tumor growth and a nonsignificant increase in mammary tumor incidence and shorter tumor latency. These tumor phenotypes were linked to mammary tissue inhibition of AMPK, a central metabolic sensor, and increased mTOR activity. In conclusion, our findings support a role for DDT exposure from the paternal lineage in metabolic dysfunction and increased breast cancer development in the offspring. Defining the mechanism by which paternal exposures to EDC such as DDT can promote breast cancer development in offspring is critical to identifying early detection/preventive approaches or treatments for this malignancy in a subset of women. Citation Format: Raquel Santana da Cruz, Hong Cao, Camile Fontelles, Apsra Nasir, Volkan Tekam, M. Idalia Cruz, Lu Jin, Sonia de Assis. Preconception paternal DDT exposure and programming of metabolic dysfunction and breast cancer in offspring [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr A03.

Consequences of Parental Opioid Exposure on Neurophysiology, Behavior, and Health in the Next Generations.

Substance abuse and the ongoing opioid epidemic represents a large societal burden. This review will consider the long-term impact of opioid exposure on future generations. Prenatal, perinatal, and preconception exposure are reviewed with discussion of both maternal and paternal influences. Opioid exposure can have long-lasting effects on reproductive function, gametogenesis, and germline epigenetic programming, which can influence embryogenesis and alter the developmental trajectory of progeny. The potential mechanisms by which preconception maternal and paternal opioid exposure produce deleterious consequences on the health, behavior, and physiology of offspring that have been identified by clinical and animal studies will be discussed. The timing, nature, dosing, and duration of prenatal opioid exposure combined with other important environmental considerations influence the extent to which these manipulations affect parents and their progeny. Epigenetic inheritance refers to the transmission of environmental insults across generations via mechanisms independent of the DNA sequence. This topic will be further explored in the context of prenatal, perinatal, and preconception opioid exposure for both the maternal and paternal lineage.

Association between maternal exposure to PM10 and polydactyly and syndactyly: A population-based case-control study in Liaoning province, China

BackgroundThe number of studies on air pollution with birth defects as the primary outcome has increased dramatically over the past two decades, but the potential role of specific air pollutants in congenital limb anomalies remains unclear. ObjectivesTo evaluate associations between preconception and first-trimester PM10 exposure and polydactyly and syndactyly in a population-based case-control study. MethodsPolydactyly cases (n = 2605), syndactyly cases (n = 595), and controls without any birth defects (n = 7950) born between 2010 and 2015 were selected from the Maternal and Child Health Certificate Registry of Liaoning Province. The monthly mean PM10 concentrations were obtained from 75 air monitoring stations, and the exposure assessment was based on the mean concentration of all stations in mother's residential city. A multivariable logistic regression model was constructed to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). ResultsPM10 exposure was positively associated with the risks of polydactyly (preconception: aORT3 vs. T1 = 1.95, 95% CI 1.56–2.45, aOR = 1.06, 95% CI 1.01–1.10 [per 10-μg/m3 increment]; first-trimester: aORT3 vs. T1 = 2.51, 95% CI 2.00–3.15) and syndactyly (preconception: aORT3 vs. T1 = 2.86, 95% CI 1.98–4.13, aOR = 1.11, 95% CI 1.03–1.20 [per 10-μg/m3 increment]; first-trimester: aORT3 vs. T1 = 3.10, 95% CI 2.11–4.56). Analyses based on single month exposure windows basically showed similar positive associations. Additionally, these findings were robust in sensitivity analyses and broadly consistent across subgroups. ConclusionOur study suggest that preconception and first-trimester PM10 exposures are related to increased risks of polydactyly and syndactyly.

Pre-conceptional exposure to multiwalled carbon nanotubes suppresses antibody production in mouse offspring

Prenatal particle exposure has been shown to increase allergic responses in offspring. Carbon nanotubes (CNTs) possess immunomodulatory properties, but it is unknown whether maternal exposure to CNTs interferes with offspring immune development. Here, C57Bl/6J female mice were intratracheally instilled with 67 of μg multiwalled CNTs on the day prior to mating. After weaning, tolerance and allergy responses were assessed in the offspring. Offspring of CNT-exposed (CNT offspring) and of sham-exposed dams (CTRL offspring) were intranasally exposed to ovalbumin (OVA) once weekly for 5 weeks to induce airway mucosal tolerance. Subsequent OVA sensitization and aerosol inhalation caused low or no OVA-specific IgE production and no inflammation. However, the CNT offspring presented with significantly lower OVA-specific IgG1 levels than CTRL offspring. In other groups of 5-week-old offspring, low-dose sensitization with OVA and subsequent OVA aerosol inhalation led to significantly lower OVA-specific IgG1 production in CNT compared to CTRL offspring. OVA-specific IgE and airway inflammation were non-significantly reduced in CNT offspring. The immunomodulatory effects of pre-gestational exposure to multiwalled CNTs were unexpected, but very consistent. The observations of suppressed antigen-specific IgG1 production may be of importance for infection or vaccination responses and warrant further investigation.

Increased risk of gestational diabetes mellitus in women with higher prepregnancy ambient PM2.5 exposure

BackgroundAir pollution is a serious environmental problem in China. This study was designed to investigate whether exposure to particulate matter with an aerodynamic diameter ≤ 2.5 μm (PM2.5) before pregnancy is associated with gestational diabetes mellitus (GDM) and fasting glucose in China. MethodsWe recruited subjects and collected clinical data from the Nanjing Maternity and Child Health Care Hospital from July 2016 to October 2017. A series of validated land-use regression (LUR) models were built to assess individual exposure to PM2.5 in a 1 × 1 km area at both work and home addresses following a time-weighted pattern. Multiple linear regression and logistic regression analyses were performed to examine the association between PM2.5 exposure and GDM and fasting glucose. ResultsIn total, 11,639 of 16,995 women were included in the final analysis. Among the 11,639 women, 2776 (23.85%) had GDM. Individual exposure to PM2.5 within three months before pregnancy ranged from 21.58 to 85.92 μg/m3. Positive associations were observed among the interquartile ranges (IQRs) of exposure to PM2.5 within three months before pregnancy and GDM (OR = 2.61, 95% CI: 1.40–4.93, p < .01) as well as fasting glucose levels (β = 0.57, 95% CI: 0.45–0.68, p < .01). The diabetogenic effects of PM2.5 gradually increased from the first month before pregnancy, peaked in the second month and then gradually decreased until the third month when the week-specific exposure were analyzed to identify the sensitive time window. ConclusionOur study confirmed that higher exposure to PM2.5 within three months before pregnancy is significantly associated with increased risk of GDM and elevated fasting glucose levels, reflecting the importance of preconceptional environmental exposure in the development of maternal GDM.

Preconception telomere length as a novel maternal biomarker to assess the risk of spina bifida in the offspring.

BackgroundPericonception interactions between maternal conditions and environmental and genetic factors are involved in the pathogenesis and prevention of neural tube defects (NTD), such as spina bifida. These factors have in common that they can impair the oxidative pathway, resulting in excessive (chronic) oxidative stress and inflammation.MethodsReview of the literature concerning underlying mechanisms and biomarkers of aging particularly during reproduction. A number of molecular markers for biological aging have been identified, including telomere length (TL). Excessive telomere shortening is an index of senescence, causes genomic instability and is associated with a higher risk of age‐related diseases. Furthermore, TL shortening is associated with the similar environmental and lifestyle exposures associated with NTD risk.ResultsEmbryonic mice deficient in the telomerase gene show shorter TL and failure of closure of the neural tube as the main defect, suggesting that this developmental process is among the most sensitive to telomere loss and chromosomal instability.ConclusionsFrom this background, we hypothesize that preconceptional long term exposure to harmful environmental and lifestyle risk factors accelerates a woman's aging process, which can be measured by TL, and thereby her underlying risk of NTD offspring. Alternatively, it might be that women with an increased NTD risk already exhibit a more advanced biological age before the onset of pregnancy compared to women of identical calendar age.

The aryl hydrocarbon receptor mediates sex ratio distortion in the embryos sired by TCDD-exposed male mice

Many reports describe an association between preconceptional paternal exposure to environmental chemicals, including the persistent organic pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) with an increased number of female offspring. We chronically treated wild-type C57BL/6 male mice with TCDD to investigate a role for the aryl hydrocarbon receptor (AHR) transcription factor. These mice had a 14 % lower male:female sex ratio than control mice, which was not observed in TCDD-treated Ahr knock out mice. AHR target genes Cyp1a1 and Ahrr were upregulated in the liver and testis of WT mice and Ahr expression was higher in the epididymis (2-fold) and liver (18-fold) than in whole testis tissue. The AHR protein was localized to round spermatids, elongating spermatids, and Leydig cells in the testis of WT mice. These studies demonstrate AHR involvement in the sex ratio distortion of TCDD-exposed males and the need for evaluating the molecular and genetic mechanism of this process.

Nontargeted identification of per- and polyfluoroalkyl substances in human follicular fluid and their blood-follicle transfer

The female reproductive toxicity of per- and polyfluoroalkyl substances (PFAS) has raised concerns, but knowledge about their human preconception exposure is limited. In this study, 15 emerging PFAS were identified in follicular fluid samples from healthy women by using high-resolution mass spectrometry, and Cl-substituted perfluoroalkyl ether sulfonates (Cl-PFESAs) including 4:2, 5:2, 6:2, and 8:2 Cl-PFESAs, 4:4 C8 perfluoroalkyl ether sulfonate (PFESA), C8 perfluoroalkyl ether carboxylate (PFECA), and C8 polyether PFECA (Po-PFECA) were detected in over 50% of 28 follicular fluid samples. Ten legacy PFAS were also detected, and the geometric mean concentration of PFOS was the highest (4.82 ng/mL), followed by PFOA (4.60 ng/mL), 6:2 Cl-PFESA (1.09 ng/mL), PFHxS (0.515 ng/mL), PFNA (0.498 ng/mL), and C8 PFECA (0.367 ng/mL). The blood-follicle transfer efficiencies for PFCAs decreased with increasing chain length (0.96 for PFHpA, 0.56 for PFTriDA), and the transfer efficiencies of C8 PFECA (0.78) was significantly higher than that of PFOA (0.76). The transfer efficiencies of 4:2 Cl-PFESA (0.73), 6:2 Cl-PFESA (0.75) and 8:2 Cl-PFESA (0.91) were significantly higher than that (0.70) of PFOS (p = 0.028, 0.026 and 0.002, respectively). This study constitutes the first report of the human oocyte exposure to emerging PFAS and their blood-follicle transfer abilities.

Association of Parental Preconception Exposure to Phthalates and Phthalate Substitutes With Preterm Birth

Although phthalate exposure during pregnancy has been associated with preterm birth, the association of preconception exposure in either parent with preterm birth constitutes a knowledge gap. To examine the association of paternal and maternal preconception urinary concentrations of biomarkers of phthalates and phthalate substitutes with singleton preterm birth. This study, conducted at an academic fertility center in Boston, Massachusetts, included a prospective preconception cohort of subfertile couples comprising 419 mothers and 229 fathers and their 420 live-born singleton offspring born between January 1, 2005, and December 31, 2018. Statistical analysis was performed from August 1 to October 31, 2019. Urinary concentrations of metabolites of phthalates and phthalate substitutes obtained before conception. Gestational age was abstracted from delivery records and validated using the American College of Obstetricians and Gynecologists guidelines for births after medically assisted reproduction. The risk ratio (RR) of preterm birth (live birth before 37 completed weeks' gestation) was estimated in association with urinary concentrations of 11 individual phthalate metabolites, the molar sum of 4 di-(2-ethylhexyl) phthalate (ΣDEHP) metabolites, and 2 metabolites of 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH, a nonphthalate plasticizer substitute) using modified Poisson regression models adjusted for covariates. The mean (SD) age of the 419 mothers was 34.7 (4.0) years, the mean (SD) age of the 229 fathers was 36.0 (4.5) years, and the mean (SD) gestational age of the 420 singleton children (217 boys) was 39.3 (1.7) weeks, with 34 (8%) born preterm. In adjusted models, maternal preconception ΣDEHP concentrations (RR, 1.50; 95% CI, 1.09-2.06; P = .01) and cyclohexane-1,2-dicarboxylic acid monohydroxy isononyl ester (MHiNCH, a metabolite of DINCH) concentrations (RR, 1.70; 95% CI, 0.89-3.24; P = .11) were associated with an increased risk of preterm birth. After additional adjustment for prenatal ΣDEHP or MHiNCH concentrations, the association of maternal preconception exposure to ΣDEHP and preterm birth remained robust (RR, 1.69; 95% CI, 1.17-2.44; P = .006), while the association of maternal preconception exposure to MHiNCH and preterm birth was attenuated (RR, 1.17; 95% CI, 0.49-2.81; P = .72). The remaining urinary metabolites examined in either parent showed no association with preterm birth. In this prospective cohort of subfertile couples, maternal preconception exposure to ΣDEHP metabolites was associated with an increased risk of preterm birth. The results suggest that female exposure to select phthalate plasticizers during the preconception period may be a potential risk factor for adverse pregnancy outcomes, which may need to be considered in preconception care strategies.

The Australian and New Zealand Intergenerational Cohort Consortium: a study protocol for investigating mental health and well-being across generations

The Australian New Zealand Intergenerational Cohort Consortium (ANZ-ICC) brings together three of the longest running intergenerational cohort studies in Australia and New Zealand to examine the extent to which preconception parental life histories (from infancy to parenthood) predict next generation early health and development. The aims are threefold: (1) to describe pathways of advantage that strengthen emotional health and well-being from one generation to the next, (2) to describe pathways of disadvantage that perpetuate cycles of emotional and behavioural problems across generations, and (3) to identify modifiable factors capable of breaking intergenerational cycles. The Victorian Intergenerational Health Cohort Study has followed 1,943 young Australians from adolescence to adulthood across ten waves since 1992, and 1,030 offspring from pregnancy to early childhood since 2006. The Australian Temperament Project Generation 3 Study has followed 2,443 young Australians from infancy to adulthood across 15 waves since 1983, and 1170 offspring from pregnancy to early childhood since 2012. The Dunedin Multidisciplinary Health and Development Study Parenting Study has followed 1,037 young New Zealanders across 15 waves since 1972, and 730 offspring in early childhood since 1994. Cross-cohort replication analyses will be conducted for common preconception exposures and next generation offspring outcomes, while integrated data analysis of pooled data will be used for rare exposures and outcomes. The ANZ-ICC represents a unique collaboration that bridges the disciplines of lifecourse epidemiology, biostatistics, developmental psychology and psychiatry, to study the role of parental preconception exposures on next generation health and development.

Maternal and paternal preconception exposure to phenols and preterm birth

BackgroundPhenol exposure during pregnancy has been associated with preterm birth, but the potential effect of preconception exposure in either parent is unknown. There is a growing body of evidence to suggest that the preconception period is a critical window of vulnerability for adverse pregnancy outcomes. ObjectiveWe examined whether maternal and paternal preconception urinary concentrations of select phenols were associated with the risk of preterm birth among couples attending fertility care. MethodsThe analysis included 417 female and 229 male participants of the Environment and Reproductive Health (EARTH) Study who gave birth to 418 singleton infants between 2005 and 2018 and for whom we had phenol biomarkers quantified in at least one urine sample collected before conception. Mothers and fathers provided an average of 4 and 3 urine samples during the preconception period, respectively. We calculated the geometric mean of bisphenol A (BPA), bisphenol S (BPS), benzophenone-3, triclosan, and the molar sum of parabens (ΣParabens) urinary concentrations to estimate each participant’s preconception exposure. Risk ratios (RRs) of preterm birth (live birth before 37 completed weeks’ gestation) were estimated using modified Poisson regression models adjusted for covariates. ResultsThe mean (SD) gestational age among singletons was 39.3 (1.7) weeks with 8% born preterm. A natural log-unit increase in maternal preconception BPA (RR 1.94; 95% CI: 1.20, 3.14) and BPS (RR 2.42; 95% CI: 1.01, 5.77) concentration was associated with an increased risk of preterm birth. These associations remained after further adjustment for maternal prenatal and paternal preconception biomarker concentrations. Paternal preconception ΣParabens concentrations showed a possible elevated risk of preterm birth (RR 1.36; 95% CI: 0.94, 1.96). No consistent pattern of association was observed for benzophenone-3 or triclosan biomarkers in either parent. DiscussionMaternal preconception urinary BPA and BPS concentrations, as well as paternal preconception urinary parabens concentrations were prospectively associated with a higher risk of preterm birth. Subfertile couples’ exposure to select phenols during the preconception period may be an unrecognized risk factor for adverse pregnancy outcomes.

In utero exposures to electronic-cigarette aerosols impair the Wnt signaling during mouse lung development.

Currently, more than 9 million American adults, including women of childbearing age, use electronic-cigarettes (e-cigs). Further, the prevalence of maternal vaping now approaching 10% is similar to that of maternal smoking. Little, however, is known about the effects of fetal exposures to nicotine-rich e-cig aerosols on lung development. In this study, we assessed whether in utero exposures to e-cig aerosols compromised lung development in mice. A third-generation e-cig device was used to expose pregnant BALB/c mice by inhalation to 36 mg/mL of nicotine cinnamon-flavored e-cig aerosols for 14-31 days. This included exposures for either 12 days before mating plus during gestation (preconception groups) or only during gestation (prenatal groups). Respective control mice were exposed to filtered air. Subgroups of offspring were euthanized at birth or at 4 wk of age. Compared with respective air-exposed controls, both preconception and prenatal exposures to e-cig aerosols significantly decreased the offspring birth weight and body length. In the preconception group, 7 inflammation-related genes were downregulated, including 4 genes common to both dams and fetuses, denoting an e-cig immunosuppressive effect. Lung morphometry assessments of preconception e-cig-exposed offspring showed a significantly increased tissue fraction at birth. This result was supported by the downregulation of 75 lung genes involved in the Wnt signaling, which is essential to lung organogenesis. Thus, our data indicate that maternal vaping impairs pregnancy outcomes, alters fetal lung structure, and dysregulates the Wnt signaling. This study provides experimental evidence for future regulations of e-cig products for pregnant women and developmentally vulnerable populations.

The preconception environment and sperm epigenetics.

Infertility is a common reproductive disorder, with male factor infertility accounting for approximately half of all cases. Taking a paternal perceptive, recent research has shown that sperm epigenetics, such as changes in DNA methylation, histone modification, chromatin structure, and noncoding RNA expression, can impact reproductive and offspring health. Importantly, environmental conditions during the preconception period has been demonstrated to shape sperm epigenetics. To provide an overview on epigenetic modifications that regulate normal gene expression and epigenetic remodeling that occurs during spermatogenesis, and to discuss the epigenetic alterations that may occur to the paternal germline as a consequence of preconception environmental conditions and exposures. We examined published literature available on databases (PubMed, Google Scholar, ScienceDirect) focusing on adult male preconception environmental exposures and sperm epigenetics in epidemiologic studies and animal models. The preconception period is a sensitive developmental window in which a variety of exposures such as toxicants, nutrition, drugs, stress, and exercise, affects sperm epigenetics. Understanding the environmental legacy of the sperm epigenome during spermatogenesis will enhance our understanding of reproductive health and improve reproductive success and offspring well-being.

Programming effects of maternal and gestational obesity on offspring metabolism and metabolic inflammation

With the increasing prevalence of obesity in women of reproductive age there is a need to understand the ramifications of this on offspring. The purpose of this study is to investigate the programming effects of maternal obesity during preconception and the preconception/gestational period on adiposity and adipose tissue inflammation in offspring using an animal model. Adult female C57Bl/6J mice were assigned either normal diet, high fat diet (HFD) prior to pregnancy, or HFD prior to and through pregnancy. Some offspring were maintained on normal diet while others started HFD later in life. Offspring were assessed for body composition and metabolic responses. Lipid storing tissues were evaluated for expansion and inflammation. Male offspring from the preconception group had the greatest weight gain, most subcutaneous adipose tissue, and largest liver mass when introduced to postnatal HFD. Male offspring of the preconception/gestation group had worsened glucose tolerance and an increase in resident (CD11c−) adipose tissue macrophages (ATMs) when exposed to postnatal HFD. Female offspring had no significant difference in any parameter between the diet treatment groups. In conclusion, this study demonstrates that prenatal and pregnancy windows have independent programming effects on offspring. Preconception exposure affects body composition and adiposity while gestation exposure affects metabolism and tissue immune cell phenotypes.