Epigenetic Memory of Early-Life Parental Perturbation: Dopamine Decrease and DNA Methylation Changes in Offspring

Early-life exposure (from postnatal day 6 to postnatal day 21) to permethrin has been associated with long-term development of dopaminergic neurodegeneration in rats. Here, we first investigated if the dopamine decrease observed following early postnatal exposure to permethrin, an oxidative stressor, can impair the dopamine level in the brain of their untreated offspring. Secondly, we evaluated whether this adverse event affects the epigenome of both directly exposed rats (F0) and their untreated offspring (F1). The results show that early-life exposure to the stressor is associated with changes in global DNA methylation and hydroxymethylation in adult age. Furthermore, parental exposure leads to a significant reduction in dopamine level in the offspring (F1) born from parents or just mothers early-life treated (72.72% and 47.35%, respectively). About 2/3 of pups from exposed mothers showed a significant reduction in dopamine level compared to controls. Global DNA methylation and hydroxymethylation impairment was associated with the F1 pups that showed reduced dopamine. This study provides pivotal evidences on intergenerational effects of postnatal exposure to permethrin emphasizing that this xenobiotic can influence the epigenetic memory of early-life parental perturbations disturbing offspring health.

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Intergenerational Effect of Early Life Exposure to Permethrin: Changes in Global DNA Methylation and in Nurr1 Gene Expression

Toxics ◽

10.3390/toxics3040451 ◽

2015 ◽

Vol 3 (4) ◽

pp. 451-461 ◽

Cited By ~ 20

Author(s):

Laura Bordoni ◽

Cinzia Nasuti ◽

Maria Mirto ◽

Fabio Caradonna ◽

Rosita Gabbianelli

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Early Life ◽

Global Dna Methylation ◽

Early Life Exposure ◽

Intergenerational Effect

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Early life social and ecological determinants of global DNA methylation in wild spotted hyenas

Molecular Ecology ◽

10.1111/mec.15174 ◽

2019 ◽

Vol 28 (16) ◽

pp. 3799-3812 ◽

Cited By ~ 3

Author(s):

Zachary M. Laubach ◽

Christopher D. Faulk ◽

Dana C. Dolinoy ◽

Luke Montrose ◽

Tamara R. Jones ◽

...

Keyword(s):

Dna Methylation ◽

Early Life ◽

Global Dna Methylation ◽

Spotted Hyenas

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Association between early-life exposure to the Great Chinese Famine and poor physical function later in life: a cross-sectional study

BMJ Open ◽

10.1136/bmjopen-2018-027450 ◽

2019 ◽

Vol 9 (7) ◽

pp. e027450

Author(s):

Tao Tao ◽

Lingyan Dai ◽

JinXiang Ma ◽

Yusi Li ◽

Zhuoyuan Guo

Keyword(s):

Physical Function ◽

Early Life ◽

Later Life ◽

Exposed Group ◽

Self Report ◽

Postnatal Exposure ◽

Cross Sectional Survey ◽

Cross Sectional ◽

Fetal Period ◽

Early Life Exposure

ObjectivesThis study aimed to evaluate the association between early-life exposure to the Great Chinese Famine (1959–1961) and the prevalence of poor physical function in midlife.DesignA population-based historical prospective study was performed as part of a wider cross-sectional survey. Exposure to famine was defined by birthdate, and participants were divided into non-exposed group, fetal-exposed group and infant-exposed group.Setting and participantsA total of 3595 subjects were enrolled into the study from the China Health and Retirement Longitudinal Study (CHARLS) 2015 based on random selection of households that had at least one member aged 45 years old and older in 28 provinces of mainland China.Main outcome measuresPhysical function status was assessed by a six-item self-report on the Barthel scale which rated basic activities of daily living (BADL).Results743 (20.7%) out of all participants were exposed to the Great Chinese Famine in their fetal periods, while 1550 (43.1%) participants were exposed at the age of an infant. The prevalence of poor physical function in the non-exposed group, fetal period-exposed group and infant period-exposed group were 12.3%, 15.5% and 17.0%, respectively. Among males, after stratification by gender and severity of famine, the prevalence of poor physical function in the fetal period was significantly higher (OR 2.40, 95% CI 1.18 to 4.89, p=0.015) than the non-exposed group in severely affected areas, even after adjusting for the number of chronic diseases, place of residence, smoking and alcohol drinking habits, marital status, educational level and body mass index. A similar connection between prenatal and early postnatal exposure to the Great Chinese Famine and the prevalence of poor physical function in midlife, however, was not observed from female adults.ConclusionsMales who were exposed to the Great Chinese Famine (1959–1961) present considerably decreased physical function in their later life.

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Analysis of DNA Methylation Changes in Mice Mediated by Early‐life Exposure to the Antidepressant S‐citalopram

The FASEB Journal ◽

10.1096/fasebj.2020.34.s1.06398 ◽

2020 ◽

Vol 34 (S1) ◽

pp. 1-1

Author(s):

Meghan Rodriquez ◽

Madhur Shetty ◽

Elizabeth Black ◽

Matthew Kretschmar ◽

Danielle Perley ◽

...

Keyword(s):

Dna Methylation ◽

Early Life ◽

Early Life Exposure

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Famine and Trajectories of Body Mass Index, Waist Circumference, and Blood Pressure in Two Generations: Results From the CHNS From 1993–2015

Hypertension ◽

10.1161/hypertensionaha.121.18022 ◽

2021 ◽

Author(s):

Jie Li ◽

Qingling Yang ◽

Ran An ◽

Howard D. Sesso ◽

Victor W. Zhong ◽

...

Keyword(s):

Blood Pressure ◽

Body Mass Index ◽

Waist Circumference ◽

Body Mass ◽

Early Life ◽

Metabolic Diseases ◽

Nutrition Survey ◽

Mixed Effect ◽

Parental Exposure ◽

Early Life Exposure

Early-life exposures play key roles in the development of metabolic diseases. Whether such effects exist beyond one generation remains unclear. This study aimed to determine the transgenerational association of early-life exposure to the Chinese famine of 1959 to 1962 with the trajectories of body mass index (BMI), waist circumference (WC), and blood pressure (BP) in 2 consecutive generations. We included 21 106 F1 observations born between 1954 and 1967 (median age: 45 years) and 1926 F2 observations (median age: 23 years) from the longitudinal household-based China Health and Nutrition Survey from 1993 to 2015. Trajectories of BMI, WC, systolic BP, and diastolic BP were fitted and compared between groups using linear mixed effect models. Early-life exposure to famine was associated with increased BMI, WC, and BP in 2 consecutive generations with sex and age disparities. In F1, famine was associated with increased BMI, WC, systolic BP, and diastolic BP, especially in men or those aged older than 50 years ( P ranged from <0.001 to 0.02). In F2 men but not women, the parental exposure to famine was associated with 0.59 kg/m 2 ([95% CI, 0.10–1.08], P =0.02) increase in BMI. In F2 aged ≥25 years but not those younger ones, the parental exposure to famine was associated with increased BMI (0.83 kg/m 2 [0.14–1.51] , P =0.03), systolic BP (2.04 mm Hg [0.20–3.88], P =0.03), and diastolic BP (1.73 mm Hg [0.28–3.18], P =0.02). The effects of an adverse developmental environment through famine in early life on BMI and BP later in life may persist beyond one generation.

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Parental transgenerational epigenetic inheritance related to dietary crude oil exposure in Danio rerio

Journal of Experimental Biology ◽

10.1242/jeb.222224 ◽

2020 ◽

Vol 223 (16) ◽

pp. jeb222224

Author(s):

Naim M. Bautista ◽

Amélie Crespel ◽

Janna Crossley ◽

Pamela Padilla ◽

Warren Burggren

Keyword(s):

Dna Methylation ◽

Crude Oil ◽

Control Diet ◽

Epigenetic Inheritance ◽

Heart Tissue ◽

Global Dna Methylation ◽

Parental Exposure ◽

Water Accommodated Fractions ◽

Parental Lines ◽

Oil Exposure

ABSTRACTTransgenerational inheritance from both parental lines can occur by genetic and epigenetic inheritance. Maternal effects substantially influence offspring survival and fitness. However, investigation of the paternal contribution to offspring success has been somewhat neglected. In the present study, adult zebrafish were separated into female and male groups exposed for 21 days to either a control diet or to a diet containing water accommodated fractions of crude oil. Four F1 offspring groups were obtained: (1) control (non-exposed parents), (2) paternally exposed, (3) maternally exposed and (4) dual-parent-exposed. To determine the maternal and paternal influence on their offspring, we evaluated responses from molecular to whole organismal levels in both generations. Growth rate, hypoxia resistance and heart rate did not differ among parental groups. However, global DNA methylation in heart tissue was decreased in oil-exposed fish compared with control parents. This decrease was accompanied by an upregulation of glycine N-methyltransferase. Unexpectedly, maternal, paternal and dual exposure all enhanced survival of F1 offspring raised in oiled conditions. Regardless of parental exposure, however, F1 offspring exposed to oil exhibited bradycardia. Compared with offspring from control parents, global DNA methylation was decreased in the three offspring groups derived from oil-exposed parents. However, no difference between groups was observed in gene regulation involved in methylation transfer, suggesting that the changes observed in the F1 populations may have been inherited from both parental lines. Phenotypic responses during exposure to persistent environmental stressors in F1 offspring appear to be influenced by maternal and paternal exposure, potentially benefitting offspring populations to survive in challenging environments.

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Impact of mothers' early life exposure to low or high folate on progeny outcome and DNA methylation patterns

Environmental Epigenetics ◽

10.1093/eep/dvaa018 ◽

2020 ◽

Vol 6 (1) ◽

Author(s):

Lundi Ly ◽

Donovan Chan ◽

Mylène Landry ◽

Camille Angle ◽

Josée Martel ◽

...

Keyword(s):

Dna Methylation ◽

Folic Acid ◽

Early Life ◽

Daily Intake ◽

Oocyte Quality ◽

Next Generation ◽

Early Life Exposure ◽

Generation Progeny ◽

F2 Generation ◽

Methylation Patterns

Abstract The dynamic patterning of DNA and histone methylation during oocyte development presents a potentially susceptible time for epigenetic disruption due to early life environmental exposure of future mothers. We investigated whether maternal exposure to folic acid deficient and supplemented diets starting in utero could affect oocytes and cause adverse developmental and epigenetic effects in next generation progeny. Female BALB/c mice (F0) were placed on one of four amino acid defined diets for 4 weeks before pregnancy and throughout gestation and lactation: folic acid control (rodent recommended daily intake; Ctrl), 7-fold folic acid deficient, 10-fold folic acid supplemented or 20-fold folic acid supplemented diets. F1 female pups were weaned onto Ctrl diets, mated to produce the F2 generation and the F2 offspring were examined at E18.5 for developmental and epigenetic abnormalities. Resorption rates were increased and litter sizes decreased amongst F2 E18.5-day litters in the 20-fold folic acid supplemented group. Increases in abnormal embryo outcomes were observed in all three folic acid deficient and supplemented groups. Subtle genome-wide DNA methylation alterations were found in the placentas and brains of F2 offspring in the 7-fold folic acid deficient , 10-fold folic acid supplemented and 20-fold folic acid supplemented groups; in contrast, global and imprinted gene methylation were not affected. The findings show that early life female environmental exposures to both low and high folate prior to oocyte maturation can compromise oocyte quality, adversely affecting offspring of the next generation, in part by altering DNA methylation patterns.

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