Second trimester extracellular microRNAs in maternal blood and fetal growth: An exploratory study

Healthy feto-maternal communication is critical during pregnancy and is orchestrated by the placenta. Dysfunction of the placenta leads to fetal growth complications; however, the underlying biological mechanisms have yet to be fully elucidated. Circulating extracellular microRNAs (exmiRNAs) in the blood have been implicated in cell-to-cell communication. Therefore, exmiRNAs may provide useful biological information about communication between the mother, the fetus, and the placenta during pregnancy. We used logistic regression to determine the association of exmiRNAs with abnormal fetal growth by comparing mothers of infants classified as small-for-gestational age (SGA) (n = 36) and large-for-gestational age (LGA) (n = 13) to appropriate-for-gestational age (AGA), matched by gestational age at delivery and infant sex. In addition, we used linear regression to determine associations between exmiRNAs and birth weight-for-gestational age (BWGA) z-score (n = 100), adjusting for maternal age, body mass index, and parity. We found that higher levels of miR-20b-5p, miR-942-5p, miR-324-3p, miR-223-5p, and miR-127-3p in maternal serum were associated with lower odds for having a SGA vs. AGA infant, and higher levels of miR-661, miR-212-3p, and miR-197-3p were associated with higher odds for having a LGA vs. AGA infant. We also found associations between miR-483-5p, miR-10a-5p, miR-204-5p, miR-202-3p, miR-345-5p, miR-885-5p, miR-127-3p, miR-148b-3p, miR-324-3p, miR-1290, miR-597-5p, miR-139-5p, miR-215-5p, and miR-99b-5p and BWGA z-score. We also found sex-specific associations with exmiRNAs and fetal growth. Our findings suggest that exmiRNAs circulating in maternal blood at second trimester are associated with fetal growth. Validation of our findings may lead to the development of minimally-invasive biomarkers of fetal growth during pregnancy

Particulate Air Pollution and Fasting Blood Glucose in Nondiabetic Individuals: Associations and Epigenetic Mediation in the Normative Aging Study, 2000–2011

Background: Among nondiabetic individuals, higher fasting blood glucose (FBG) independently predicts diabetes risk, cardiovascular disease, and dementia. Ambient PM2.5 (particulate matter with aerodynamic diameter ≤ 2.5 μm) is an emerging determinant of glucose dysregulation. PM2.5 effects and mechanisms are understudied among nondiabetic individuals. Objectives: Our goals were to investigate whether PM2.5 is associated with an increase in FBG and to explore potential mediating roles of epigenetic gene regulation. Methods: In 551 nondiabetic participants in the Normative Aging Study, we measured FBG, and DNA methylation of four inflammatory genes (IFN-γ, IL-6, ICAM-1, and TLR-2), up to four times between 2000 and 2011 (median = 2). We estimated short- and medium-term (1-, 7-, and 28-day preceding each clinical visit) ambient PM2.5 at each participant’s address using a validated hybrid land-use regression satellite-based model. We fitted covariate-adjusted regression models accounting for repeated measures. Results: Mean FBG was 99.8 mg/dL (SD = 10.7), 18% of the participants had impaired fasting glucose (IFG; i.e., 100–125 mg/dL FBG) at first visit. Interquartile increases in 1-, 7-, and 28-day PM2.5 were associated with 0.57 mg/dL (95% CI: 0.02, 1.11, p = 0.04), 1.02 mg/dL (95% CI: 0.41, 1.63, p = 0.001), and 0.89 mg/dL (95% CI: 0.32, 1.47, p = 0.003) higher FBG, respectively. The same PM2.5 metrics were associated with 13% (95% CI: –3%, 33%, p = 0.12), 27% (95% CI: 6%, 52%, p = 0.01) and 32% (95% CI: 10%, 58%, p = 0.003) higher odds of IFG, respectively. PM2.5 was negatively correlated with ICAM-1 methylation (p = 0.01), but not with other genes. Mediation analysis estimated that ICAM-1 methylation mediated 9% of the association of 28-day PM2.5 with FBG. Conclusions: Among nondiabetics, short- and medium-term PM2.5 were associated with higher FBG. Mediation analysis indicated that part of this association was mediated by ICAM-1 promoter methylation. Citation: Peng C, Bind MA, Colicino E, Kloog I, Byun HM, Cantone L, Trevisi L, Zhong J, Brennan K, Dereix AE, Vokonas PS, Coull BA, Schwartz JD, Baccarelli AA. 2016. Particulate air pollution and fasting blood glucose in nondiabetic individuals: associations and epigenetic mediation in the Normative Aging Study, 2000–2011. Environ Health Perspect 124:1715–1721; http://dx.doi.org/10.1289/EHP18

Long noncoding RNA expression in the cervix mid-pregnancy is associated with the length of gestation at delivery

<p>Infants born preterm are at increased risk of multiple morbidities and mortality. Why some women deliver preterm remains poorly understood. Prior studies have shown that cervical microRNA expression and DNA methylation are associated with the length of gestation. However, no study has examined the role of long noncoding RNAs (lncRNAs) in the cervix during pregnancy. To determine whether expression of lncRNAs is associated with length of gestation at delivery, we analyzed RNA from cervical swabs obtained from 78 women during pregnancy (mean 15.5, SD 5.0, weeks of gestation) who were participating in the Spontaneous Prematurity and Epigenetics of the Cervix (SPEC) Study in Boston, MA, USA. We used a PCR-based platform and found that 9 lncRNAs were expressed in at least 50% of the participants. Of these, a doubling of the expression of <i>TUG1, TINCR</i>, and <i>FALEC</i> was associated with shorter lengths of gestation at delivery [2.8 (95% CI: 0.31, 5.2); 3.3 (0.22, 6.3); and 4.5 (7.3, 1.6) days shorter respectively]. Of the lncRNAs analyzed, none was statistically associated with preterm birth, but expression of <i>FALEC</i> was 2.6-fold higher in women who delivered preterm vs. term (<i>P </i>= 0.051). These findings demonstrate that lncRNAs can be measured in cervical samples obtained during pregnancy and are associated with subsequent length of gestation at delivery. Further, this study supports future work to replicate these findings in other cohorts and perform mechanistic studies to determine the role of lncRNAs in the cervix during pregnancy.</p