Mother’s Pre-pregnancy BMI and Placental Candidate miRNAs: Findings from the ENVIRONAGE Birth Cohort

Abstract

There is increasing evidence that the predisposition for development of chronic diseases arises at the earliest times of life. In this context, maternal pre-pregnancy weight might modify fetal metabolism and the child’s predisposition to develop disease later in life. The aim of this study is to investigate the association between maternal pre-pregnancy body mass index (BMI) and miRNA alterations in placental tissue at birth. In 211 mother-newborn pairs from the ENVIRONAGE birth cohort, we assessed placental expression of seven miRNAs important in crucial cellular processes implicated in adipogenesis and/or obesity. Multiple linear regression models were used to address the associations between pre-pregnancy BMI and placental candidate miRNA expression. Maternal pre-pregnancy BMI averaged (±SD) 23.9 (±4.1) kg/m2. In newborn girls (not in boys) placental miR-20a, miR-34a and miR-222 expression was lower with higher maternal pre-pregnancy BMI. In addition, the association between maternal pre-pregnancy BMI and placental expression of these miRNAs in girls was modified by gestational weight gain. The lower expression of these miRNAs in placenta in association with pre-pregnancy BMI, was only evident in mothers with low weight gain (<14 kg). The placental expression of miR-20a, miR-34a, miR-146a, miR-210 and miR-222 may provide a sex-specific basis for epigenetic effects of pre-pregnancy BMI.

Sex-specific associations between telomere length and candidate miRNA expression in placenta

“…We chose seven miRNAs, including miR-16, miR-20a, miR-21, miR-34a, miR-146a, miR-210 and miR-222, which all have been previously reported to be involved in important cellular processes, including inflammation [ 30 , 31 ], cell cycle regulation [ 32 , 33 ], apoptosis [ 34 , 35 ], oxidative stress [ 36 ] and cellular senescence [ 37 ]. These candidate miRNAs have been shown to be expressed in human placenta tissue or cell lines in association with environmental exposures [ 38 , 39 , 42 – 44 ], fetal developmental [ 45 – 47 ] or pathological conditions [ 46 – 52 ] during pregnancy (Fig. 1 ).…”

“…1 ). We measured these miRNAs also in the context of two early life stressors: prenatal particulate matter pollution [ 38 ] and maternal pre-pregnancy BMI [ 39 ].

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Fig. 1 Associations of candidate miRNAs expressed in human placental tissue or cell lines with environmental exposures [ 38 , 39 , 42 – 44 ], fetal development [ 45 – 47 ] or pregnancy complications [ 46 – 52 ]

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“…Placental miRNA expression has been previously shown to be influenced by maternal pre-pregnancy BMI (in some cases modified by gestational weight gain) [ 39 ], tobacco smoking [ 42 ], and gestational age [ 56 ]. Epigenetic mechanisms have been shown to be affected by temperature [ 39 , 57 ], therefore adjustment for temperature was taken into account.…”

“…Here, we studied seven miRNAs (miR-16, miR-20a, miR-21, miR-34a, miR-146a, miR-210 and miR-222), involved in fundamental biological processes such as inflammation (miR-21, miR-146a) [ 30 , 31 ], cell cycle regulation (miR-16, miR-20a, miR-21, miR-34a, miR-210, miR-222) [ 32 , 33 ], apoptosis (miR-16, miR-21) [ 34 , 35 ], oxidative stress (miR-210) [ 36 ] and cellular senescence (miR-20a, miR-21, miR-34a, miR-146a, miR-210) [ 37 ]. We have previously shown that placental miRNA expression, including miR-20a, miR-21, miR-34a, miR-146a, miR-210 and miR-222, is linked to maternal exposure to air pollution (PM 2.5 and NO 2 ) [ 38 ] and/or pre-pregnancy BMI [ 39 ]. The cellular processes in which these miRNAs are involved, interact with the biology of healthy aging [ 18 , 40 ].…”