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Pregnancy Timeline by SemestersFetal liver is producing blood cellsHead may position into pelvisBrain convolutions beginFull TermWhite fat begins to be madeWhite fat begins to be madeHead may position into pelvisImmune system beginningImmune system beginningPeriod of rapid brain growthBrain convolutions beginLungs begin to produce surfactantSensory brain waves begin to activateSensory brain waves begin to activateInner Ear Bones HardenBone marrow starts making blood cellsBone marrow starts making blood cellsBrown fat surrounds lymphatic systemFetal sexual organs visibleFinger and toe prints appearFinger and toe prints appearHeartbeat can be detectedHeartbeat can be detectedBasic Brain Structure in PlaceThe Appearance of SomitesFirst Detectable Brain WavesA Four Chambered HeartBeginning Cerebral HemispheresFemale Reproductive SystemEnd of Embryonic PeriodEnd of Embryonic PeriodFirst Thin Layer of Skin AppearsThird TrimesterSecond TrimesterFirst TrimesterFertilizationDevelopmental Timeline
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Home | Pregnancy Timeline | News Alerts |News Archive Sep 6, 2013

 

"The current dogma is that DNA methylation marks are set
during early development and are mainly persistent thereafter.
However, there were no data in humans to either support
or refute this hypothesis. We set out to fill this data gap."

Julie Herbstman, PhD, lead author, assistant professor of
Environmental Health Sciences at the Mailman School.





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DNA methylation changes in pregnancy persist into childhood—and perhaps last forever

Even before they are born, babies accumulate changes in their DNA through a process called DNA methylation that may interfere with gene expression, and in turn, their health as they grow up. But until now it's been unclear just how long these changes persist.

In a new study, researchers at the Columbia Center for Children's Environmental Health at the Mailman School of Public Health establish that signs of DNA methylation persist through early childhood, suggesting the factors that influence these changes during or before pregnancy could have effects throughout life.

The study, published in an online edition of PLOS ONE, is the first to look at DNA methylation changes over time in children.

"The current dogma is that DNA methylation marks are set during early development and are mainly persistent thereafter. However, there were no data in humans to either support or refute this hypothesis. We set out to fill this data gap," explains lead author Julie Herbstman, PhD, assistant professor of Environmental Health Sciences at the Mailman School.

Recent evidence points to environmental exposures like arsenic, lead, and air pollution as factors in epigenetic changes—the umbrella term for DNA methylation and other alterations to gene expression that don't come from DNA mutations.


While the health impact of small changes in DNA methylation is not yet clear, there is concern that alterations caused by environmental exposures during important periods of development could have effects across a lifetime.


Generally, low levels of global DNA methylation have been linked to genomic instability, which can lead to DNA damage. (Global DNA methylation is defined as methylation levels measured in aggregate for all genetic material, not specific to one or more genes.)

Center researchers analyzed global DNA methylation levels in blood at two different time points. Cord blood was analyzed from 279 children who are part of the Center's Mothers & Newborns study in Northern Manhattan and the South Bronx. Of these children, 165 also had blood collected at age 3.


The authors found that cord blood methylation was correlated with and significantly predicted the level of methylation in 3 years old. This supports the hypothesis that DNA methylation changes occurring prenatally may have lasting impacts.


The researchers examined one specific factor to see how it affected DNA methylation in children—the mother's body mass index prior to becoming pregnant. Children born to moms with high BMIs had low levels of global DNA methylation, an association that was seen again at age 3.

The new study provides further evidence that maternal factors like BMI prior to pregnancy can lead to molecular changes on an epigenetic level. The observation that these same factors continue to impact DNA methylation in blood at age 3 raises concern about the potential for pre-pregnancy and prenatal conditions to have lasting health effects.


The association between pre-pregnancy BMI and decreased global DNA methylation is of particular interest given the high proportion of obesity among women of reproductive age.

The findings point to a need for further research to understand how factors, such as high BMI before pregnancy, could influence the trajectory of a child's health.


"Understanding whether and how maternal characteristics and environmental factors during early development impact long-term child health is a critical first step in identifying targets for disease prevention," says Dr. Herbstman.

Abstract
In a longitudinal cohort of ~700 children in New York City, the prevalence of asthma (>25%) is among the highest in the US. This high risk may in part be caused by transplacental exposure to traffic-related polycyclic aromatic hydrocarbons (PAHs) but biomarkers informative of PAH-asthma relationships is lacking. We here hypothesized that epigenetic marks associated with transplacental PAH exposure and/or childhood asthma risk could be identified in fetal tissues. Mothers completed personal prenatal air monitoring for PAH exposure determination. Methylation sensitive restriction fingerprinting was used to analyze umbilical cord white blood cell (UCWBC) DNA of 20 cohort children. Over 30 DNA sequences were identified whose methylation status was dependent on the level of maternal PAH exposure. Six sequences were found to be homologous to known genes having one or more 5′-CpG island(s) (5′-CGI). Of these, acyl-CoA synthetase long-chain family member 3 (ACSL3) exhibited the highest concordance between the extent of methylation of its 5′-CGI in UCWBCs and the level of gene expression in matched fetal placental tissues in the initial 20 cohort children. ACSL3 was therefore chosen for further investigation in a larger sample of 56 cohort children. Methylation of the ACSL3 5′-CGI was found to be significantly associated with maternal airborne PAH exposure exceeding 2.41 ng/m3 (OR = 13.8; p<0.001; sensitivity = 75%; specificity = 82%) and with a parental report of asthma symptoms in children prior to age 5 (OR = 3.9; p<0.05). Thus, if validated, methylated ACSL3 5′CGI in UCWBC DNA may be a surrogate endpoint for transplacental PAH exposure and/or a potential biomarker for environmentally-related asthma. This exploratory report provides a new blueprint for the discovery of epigenetic biomarkers relevant to other exposure assessments and/or investigations of exposure-disease relationships in birth cohorts. The results support the emerging theory of early origins of later life disease development.

The current study was supported by National Institute of Environmental Health Science grants P01ES09600, R00ES017051, P30ES09089; Environmental Protection Agency grants PA RD834509, NCI R03 CA150140, the John and Wendy Neu Family Foundation, and the Trustees of the Blanchette Hooker Rockefeller Fund.

Additional co-authors include Shuang Wang, Center director Frederica P. Perera, Sally A. Lederman, Julia Vishnevetsky, Andrew G. Rundle, Lori A. Hoepner, Leena Qu, and Deliang Tang.

Original press release: http://www.eurekalert.org/pub_releases/2013-09/cums-dcd082713.php