Placental DNA methylation alterations associated with maternal tobacco smoking at the RUNX3 gene are also associated with gestational age

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From: Epigenomics(Vol. 5, Issue 6)
Publisher: Future Medicine Ltd.
Document Type: Report
Length: 6,961 words
Lexile Measure: 1580L

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Author(s): Jennifer ZJ Maccani 1 , Devin C Koestler 2 , Eugene Andrés Houseman 3 , Carmen J Marsit [*] 4 , Karl T Kelsey 1 5



epigenetics; gestational age; in utero; methylation; placenta; pregnancy; RUNX3; smoking

It has long been suspected that environmental exposures in utero can increase susceptibility to adult disease. A growing body of literature suggests that the in utero environment may play a role in the development of cardiovascular disease, diabetes and certain cancers [1-5] . The Barker hypothesis posits that the in utero environment can affect offspring, altering risk for the development of disease throughout life [6-9] . Indeed, it has been suggested that even grandmaternal exposures can affect future disease susceptibility [10] . Fetal programming in response to the in utero environment is thought to be of epigenetic origin, where heritable changes to gene expression occur without direct changes to DNA sequence [11-13] .

The placenta plays an important role in regulating fetal growth and development as it produces a number of growth factors and hormones. Additionally, the placenta exhibits a significant degree of metabolic activity, including the metabolism of potentially toxic compounds [14] . However, many toxicants are capable of crossing the placenta, acting directly or potentially by altering the metabolic function of the placenta. Environmental toxicants that cross the placenta may affect placental function by modifying the epigenetic state of the tissue, including altering DNA methylation [15,16] . Thus, epigenetic marks in the placenta can serve as a record of in utero exposure [14] .

Maternal tobacco smoking during pregnancy is associated with significant morbidity and mortality, both perinatally and later in life. Several chemicals found in tobacco smoke, including nicotine, can cross the placenta and negatively impact upon the fetus [17] . Nicotine accumulates in fetal blood and amniotic fluid [18] , and fetal nicotine levels have been shown to be 15% higher than maternal levels [19] . The detrimental effects of maternal tobacco smoking include premature birth [20,21] , low birth weight [22,23] , abnormal neurobehavioral outcomes [24] , childhood obesity [25-27] , respiratory tract diseases and sudden infant death syndrome [28] . Prenatal tobacco exposure can have damaging effects through both genetic and epigenetic mechanisms [14,29] , and maternal tobacco smoking during pregnancy is associated with altered DNA methylation patterns in the placenta [30-32] . Furthermore, DNA methylation profiles associated with gestational age have been identified [33] . We hypothesized that maternal smoking during pregnancy is associated with changes to DNA methylation in the placenta and that smoking-associated DNA methylation alterations are, in turn, associated with altered gestational age, thereby providing a biological mechanism linking this exposure to important reproductive outcomes.

Materials & methods

* Study design

A total of 206 placental samples were collected from infants delivered to the Women and Infants Hospital in Providence (RI, USA) between September 2008 and September 2009 [34] , using institutional review board-approved protocols at all involved institutions. This cohort is oversampled for small-for-gestational-age (<10th percentile of birth weight) infants and clinical intrauterine growth restricted diagnoses. Placental samples were collected within 2 h of birth and full thickness sections were taken from the maternal side of the...

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Gale Document Number: GALE|A350751098