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Placental microRNAs relate to early childhood growth trajectories
Elizabeth M Kennedy1, Karen Hermetz1, Amber Burt1
1Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, Georgia.
Insights
Placental microRNAs influence early childhood growth trajectories by targeting key signaling pathways involved in placental development. This research highlights the placenta's role in long-term infant health, supporting the Developmental Origins of Health and Disease hypothesis.
Area of Science:
- Reproductive Biology
- Developmental Biology
- Genetics and Genomics
Background:
- Poor placental function is a primary cause of intrauterine growth restriction, linked to adverse health outcomes.
- Genetic variants associated with birth weight and childhood obesity impact placental function.
- Placental microRNAs are linked to birth weight, suggesting a role beyond gestation.
Purpose of the Study:
- To investigate the relationship between placental microRNAs and early childhood growth trajectories (0-5 years).
- To explore the placenta's influence on infant development post-birth.
Main Methods:
- Utilized the SITAR package to model individual weight trajectories in 238 children from the New Hampshire Birth Cohort Study.
- Employed negative binomial generalized linear models to identify placental microRNAs associated with growth parameters.
- Controlled for covariates including sex, gestational age at birth, and maternal parity.
Main Results:
- Six placental microRNAs were significantly associated with early childhood growth trajectories (FDR < 0.1).
- Genes targeted by these microRNAs are enriched in growth factor signaling pathways (TGF/beta, EGF/R, FGF/R, IGF/R), calmodulin signaling, and NOTCH signaling.
- Specific microRNAs identified include miR-876, miR-155, Let-7c, miR-216a, and miR-629.
Conclusions:
- Placental microRNAs regulate pathways crucial for placental proliferation, differentiation, and function.
- These findings support the Developmental Origins of Health and Disease hypothesis, indicating fetal environment impacts health beyond birth.
- This study is the first to link placental molecular patterns (microRNAs) directly to early childhood growth trajectory.
Background:
Poor placental function is a common cause of intrauterine growth restriction, which in turn is associated with increased risks of adverse health outcomes. Our prior work suggests that birthweight and childhood obesity-associated genetic variants functionally impact placental function and that placental microRNA are associated with birthweight. To address the influence of the placenta beyond birth, we assessed the relationship between placental microRNAs and early childhood growth.
Methods:
Using the SITAR package, we generated two parameters that describe individual weight trajectories of children (0-5 years) in the New Hampshire Birth Cohort Study (NHBCS, n = 238). Using negative binomial generalized linear models, we identified placental microRNAs that relate to growth parameters (FDR < 0.1), while accounting for sex, gestational age at birth, and maternal parity.
Results:
Genes targeted by the six growth trajectory-associated microRNAs are enriched (FDR < 0.05) in growth factor signaling (TGF/beta: miR-876; EGF/R: miR-155, Let-7c; FGF/R: miR-155; IGF/R: Let-7c, miR-155), calmodulin signaling (miR-216a), and NOTCH signaling (miR-629).
Conclusions:
Growth-trajectory microRNAs target pathways affecting placental proliferation, differentiation and function. Our results suggest a role for microRNAs in regulating placental cellular dynamics and supports the Developmental Origins of Health and Disease hypothesis that fetal environment can have impacts beyond birth.
Impact:
We found that growth trajectory associated placenta microRNAs target genes involved in signaling pathways central to the formation, maintenance and function of placenta; suggesting that placental cellular dynamics remain critical to infant growth to term and are under the control of microRNAs. Our results contribute to the existing body of research suggesting that the placenta plays a key role in programming health in the offspring. This is the first study to relate molecular patterns in placenta, specifically microRNAs, to early childhood growth trajectory.
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