Transgenerational effects of prenatal exposure to the Dutch famine on neonatal adiposity and health in later life

Prenatal exposure to famine is associated with an increased risk of metabolic and cardiovascular diseases in the offspring at adult age. The aim of this study was to assess whether prenatal exposure to undernutrition increases the risk of stroke. This study was performed in the Dutch famine birth cohort, which consist of 2414 members who were born between 1943 and 1947 in the Netherlands. In a subsample of 1177 individuals, interviews were conducted using standardized questionnaires to obtain information about medical history (which included specific questions regarding stroke) and lifestyle. Information on stroke-related mortality was collected by linking the cohort with Statistics Netherlands. A Cox’s proportional hazard analysis was performed to calculate hazard ratios (HRs) comparing the incidence of non-fatal stroke between participants who were exposed, subdivided into early, mid and late gestation, and unexposed to famine prenatally. Three cohort members died of stroke. Of the 1177 subjects who responded to the questionnaires 49 (4.2%) survived a stroke. Unadjusted and adjusted HRs for the risk of non-fatal stroke did not show a significant difference between the unexposed and exposed subjects: HR 1.23 (95% CI 0.53–2.83), HR 1.23 (95% CI 0.53–2.82), HR 1.12 (95% CI 0.46–2.71) for those exposed in late, mid and early gestation, respectively. We were unable to find evidence for a major effect of prenatal exposure to famine on the risk of stroke in later life, although one should be aware that this study was underpowered and the study population too selected and young to identify smaller risks.

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Prenatal Exposure to Bisphenol A, E, and S Induces Transgenerational Effects on Male Reproductive Functions in Mice

Toxicological Sciences ◽

10.1093/toxsci/kfz207 ◽

2019 ◽

Vol 172 (2) ◽

pp. 303-315 ◽

Cited By ~ 5

Author(s):

Mingxin Shi ◽

Allison E Whorton ◽

Nikola Sekulovski ◽

James A MacLean ◽

Kanako Hayashi

Keyword(s):

Prenatal Exposure ◽

Corn Oil ◽

Epigenetic Modification ◽

Serum Levels ◽

Dna Methyltransferases ◽

Control Treatment ◽

Mrna Levels ◽

Transgenerational Effects ◽

Adult Testis ◽

Neonatal Testis

Abstract This study was performed to examine the transgenerational effects of bisphenol (BP) A analogs, BPE, and BPS on male reproductive functions using mice as a model. CD-1 mice (F0) were orally exposed to control treatment (corn oil), BPA, BPE, or BPS (0.5 or 50 µg/kg/day) from gestational day 7 (the presence of vaginal plug = 1) to birth. Mice from F1 and F2 offspring were used to generate F3 males. Prenatal exposure to BPA, BPE, and BPS decreased sperm counts and/or motility and disrupted the progression of germ cell development as morphometric analyses exhibited an abnormal distribution of the stages of spermatogenesis in F3 males. Dysregulated serum levels of estradiol-17β and testosterone, as well as expression of steroidogenic enzymes in F3 adult testis were also observed. In the neonatal testis, although apoptosis and DNA damage were not affected, mRNA levels of DNA methyltransferases, histone methyltransferases, and their associated factors were increased by BP exposure. Furthermore, BP exposure induced immunoreactive expression of DNMT3A in Sertoli cells, strengthened DNMT3B, and weakened H3K9me2 and H3K9me3 in germ cells of the neonatal testis, whereas DNMT1, H3K4me3, and H3K27ac were not affected. In adult testis, stage-specific DNMT3B was altered by BP exposure, although DNMT3A, H3K9me2, and H3K9me3 expression remained stable. These results suggest that prenatal exposure to BPA, BPE, and BPS induces transgenerational effects on male reproductive functions probably due to altered epigenetic modification following disruption of DNMTs and histone marks in the neonatal and/or adult testis.

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Prenatal exposure to wartime stress – long-term effect on coronary heart disease in later life

Annals of Medicine ◽

10.3109/07853890.2010.521765 ◽

2010 ◽

Vol 43 (7) ◽

pp. 555-561 ◽

Cited By ~ 5

Author(s):

Nadja K. Schreier ◽

Elena V. Moltchanova ◽

Paul A. Blomstedt ◽

Eero Kajantie ◽

Johan G. Eriksson

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Prenatal Exposure ◽

Later Life ◽

Term Effect ◽

Long Term Effect

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Prenatal Exposure to Di(2-Ethylhexyl) Phthalate Causes Long-Term Transgenerational Effects on Female Reproduction in Mice

Endocrinology ◽

10.1210/en.2017-03004 ◽

2017 ◽

Vol 159 (2) ◽

pp. 795-809 ◽

Cited By ~ 39

Author(s):

Emily Brehm ◽

Saniya Rattan ◽

Liying Gao ◽

Jodi A Flaws

Keyword(s):

Prenatal Exposure ◽

Female Reproduction ◽

Transgenerational Effects ◽

Ethylhexyl Phthalate

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Spatiotemporal Small Non-coding RNAs Expressed in the Germline as an Early Biomarker of Testicular Toxicity and Transgenerational Effects Caused by Prenatal Exposure to Nanosized Particles

Frontiers in Toxicology ◽

10.3389/ftox.2021.691070 ◽

2021 ◽

Vol 3 ◽

Author(s):

Satoshi Yokota ◽

Ken Takeda ◽

Shigeru Oshio

Keyword(s):

Prenatal Exposure ◽

Germ Cells ◽

Small Rnas ◽

Maternal Exposure ◽

Male Reproduction ◽

Reproductive Capacity ◽

Transgenerational Effects ◽

Male Germ Cells ◽

Increased Risk ◽

Non Coding Rnas

In recent years, an apparent decline in human sperm quality has been observed worldwide. One in every 5.5 couples suffers from infertility, with male reproductive problems contributing to nearly 40% of all infertility cases. Although the reasons for the increasing number of infertility cases are largely unknown, both genetic and environmental factors can be contributing factors. In particular, exposure to chemical substances during mammalian male germ cell development has been linked to an increased risk of infertility in later life owing to defective sperm production, reproductive tract obstruction, inflammation, and sexual disorders. Prenatal exposure to nanomaterials (NMs) is no exception. In animal experiments, maternal exposure to NMs has been reported to affect the reproductive health of male offspring. Male germ cells require multiple epigenetic reprogramming events during their lifespan to acquire reproductive capacity. Given that spermatozoa deliver the paternal genome to oocytes upon fertilization, we hypothesized that maternal exposure to NMs negatively affects male germ cells by altering epigenetic regulation, which may in turn affect embryo development. Small non-coding RNAs (including microRNAs, PIWI-interacting RNAs, tRNA-derived small RNAs, and rRNA-derived small RNAs), which are differentially expressed in mammalian male germ cells in a spatiotemporal manner, could play important regulatory roles in spermatogenesis and embryogenesis. Thus, the evaluation of RNAs responsible for sperm fertility is of great interest in reproductive toxicology and medicine. However, whether the effect of maternal exposure to NMs on spermatogenesis in the offspring (intergenerational effects) really triggers multigenerational effects remains unclear, and infertility biomarkers for evaluating paternal inheritance have not been identified to date. In this review, existing lines of evidence on the effects of prenatal exposure to NMs on male reproduction are summarized. A working hypothesis of the transgenerational effects of sperm-derived epigenomic changes in the F1 generation is presented, in that such maternal exposure could affect early embryonic development followed by deficits in neurodevelopment and male reproduction in the F2 generation.

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Effect of Prenatal Exposure to Bisphenols on Newborn Leucocyte Telomere Length: A Prospective Birth Cohort Study in China

10.21203/rs.3.rs-359196/v1 ◽

2021 ◽

Author(s):

Jun Liang ◽

Yantao Shao ◽

Dongping Huang ◽

Chunxiu Yang ◽

Tao Liu ◽

...

Keyword(s):

Cord Blood ◽

Telomere Length ◽

Birth Cohort ◽

Prenatal Exposure ◽

Positive Association ◽

Fold Increase ◽

Later Life ◽

Maternal Serum ◽

Birth Cohort Study ◽

Bisphenol S

Abstract Telomere length (TL) at birth is related to future diseases and long-term health. Bisphenols exhibit toxic effects and can cross the placenta barrier. However, the effect of prenatal exposure to bisphenols on newborn TL remains unknown. We aimed to explore the effects of prenatal exposure to bisphenols (i.e., bisphenol A (BPA), bisphenol B (BPB), bisphenol F (BPF), bisphenol S (BPS), and tetrabromobisphenol A (TBBPA)) on relative TL in newborns. A total of 801 mother–infant pairs were extracted from the Guangxi Zhuang Birth Cohort (GZBC). The relationships between bisphenol levels in maternal serum and relative TL in cord blood were examined by generalized linear models and restricted cubic spline (RCS) models. After adjusting for confounders, we observed a 3.19% (95% CI: -6.08%, -0.21%) reduction in relative cord blood TL among mothers ≥ 28 years with each 1-fold increase of BPS. However, each 1-fold increase of TBBPA, a 3.31% (95% CI: 0.67%, 6.01%) increased in relative cord blood TL among mothers < 28 years. The adjusted RCS models also revealed similar results (P overall < 0.05, P non-linear > 0.05). This is the first study to show a positive association between serum TBBPA levels and newborn relative TL among younger mothers. However, BPS levels were inversely correlated with TL in fetus born to older mothers. The results suggest fetuses of older pregnant women are more sensitivity to BPS exposure and accelerated aging or BPS-related diseases in later life may stem from early-life exposure.

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