Placental microRNA expression associates with birthweight through control of adipokines: results from two independent cohorts

MicroRNAs are non-coding RNAs that regulate gene expression post-transcriptionally. In the placenta, the master regulator of foetal growth and development, microRNAs shape the basic processes of trophoblast biology and specific microRNA have been associated with foetal growth. To comprehensively ass...

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Main Authors: Elizabeth M. Kennedy, Karen Hermetz, Amber Burt, Todd M. Everson, Maya Deyssenroth, Ke Hao, Jia Chen, Margaret R Karagas, Dong Pei, Devin C Koestler, Carmen J Marsit
Format: Article
Language:English
Published: Taylor & Francis Group 2021-07-01
Series:Epigenetics
Subjects:
Online Access:http://dx.doi.org/10.1080/15592294.2020.1827704
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author Elizabeth M. Kennedy
Karen Hermetz
Amber Burt
Todd M. Everson
Maya Deyssenroth
Ke Hao
Jia Chen
Margaret R Karagas
Dong Pei
Devin C Koestler
Carmen J Marsit
author_facet Elizabeth M. Kennedy
Karen Hermetz
Amber Burt
Todd M. Everson
Maya Deyssenroth
Ke Hao
Jia Chen
Margaret R Karagas
Dong Pei
Devin C Koestler
Carmen J Marsit
author_sort Elizabeth M. Kennedy
collection DOAJ
description MicroRNAs are non-coding RNAs that regulate gene expression post-transcriptionally. In the placenta, the master regulator of foetal growth and development, microRNAs shape the basic processes of trophoblast biology and specific microRNA have been associated with foetal growth. To comprehensively assess the role of microRNAs in placental function and foetal development, we have performed small RNA sequencing to profile placental microRNAs from two independent mother-infant cohorts: the Rhode Island Child Health Study (n = 225) and the New Hampshire Birth Cohort Study (n = 317). We modelled microRNA counts on infant birthweight percentile (BWP) in each cohort, while accounting for race, sex, parity, and technical factors, using negative binomial generalized linear models. We identified microRNAs that were differentially expressed (DEmiRs) with BWP at false discovery rate (FDR) less than 0.05 in both cohorts. hsa-miR-532-5p (miR-532) was positively associated with BWP in both cohorts. By integrating parallel whole transcriptome and small RNA sequencing in the RICHS cohort, we identified putative targets of miR-532. These targets are enriched for pathways involved in adipogenesis, adipocytokine signalling, energy metabolism, and hypoxia response, and included Leptin, which we further demonstrated to have a decreasing expression with increasing BWP, particularly in male infants. Overall, we have shown a robust and reproducible association of miR-532 with BWP, which could influence BWP through regulation of adipocytokines Leptin and Adiponectin.
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spelling doaj.art-01114d0d12c044539e348bfecdfdd8012023-09-21T13:09:24ZengTaylor & Francis GroupEpigenetics1559-22941559-23082021-07-0116777078210.1080/15592294.2020.18277041827704Placental microRNA expression associates with birthweight through control of adipokines: results from two independent cohortsElizabeth M. Kennedy0Karen Hermetz1Amber Burt2Todd M. Everson3Maya Deyssenroth4Ke Hao5Jia Chen6Margaret R Karagas7Dong Pei8Devin C Koestler9Carmen J Marsit10Emory UniversityEmory UniversityEmory UniversityEmory UniversityColumbia UniversityIcahn School of Medicine at Mount SinaiIcahn School of Medicine at Mount SinaiGeisel School of Medicine, Dartmouth CollegeUniversity of Kansas Medical CenterUniversity of Kansas Medical CenterEmory UniversityMicroRNAs are non-coding RNAs that regulate gene expression post-transcriptionally. In the placenta, the master regulator of foetal growth and development, microRNAs shape the basic processes of trophoblast biology and specific microRNA have been associated with foetal growth. To comprehensively assess the role of microRNAs in placental function and foetal development, we have performed small RNA sequencing to profile placental microRNAs from two independent mother-infant cohorts: the Rhode Island Child Health Study (n = 225) and the New Hampshire Birth Cohort Study (n = 317). We modelled microRNA counts on infant birthweight percentile (BWP) in each cohort, while accounting for race, sex, parity, and technical factors, using negative binomial generalized linear models. We identified microRNAs that were differentially expressed (DEmiRs) with BWP at false discovery rate (FDR) less than 0.05 in both cohorts. hsa-miR-532-5p (miR-532) was positively associated with BWP in both cohorts. By integrating parallel whole transcriptome and small RNA sequencing in the RICHS cohort, we identified putative targets of miR-532. These targets are enriched for pathways involved in adipogenesis, adipocytokine signalling, energy metabolism, and hypoxia response, and included Leptin, which we further demonstrated to have a decreasing expression with increasing BWP, particularly in male infants. Overall, we have shown a robust and reproducible association of miR-532 with BWP, which could influence BWP through regulation of adipocytokines Leptin and Adiponectin.http://dx.doi.org/10.1080/15592294.2020.1827704placental micrornaplacentamicrornabirthweighthsa-mir-532-5padipokinesleptinadiponectin
spellingShingle Elizabeth M. Kennedy
Karen Hermetz
Amber Burt
Todd M. Everson
Maya Deyssenroth
Ke Hao
Jia Chen
Margaret R Karagas
Dong Pei
Devin C Koestler
Carmen J Marsit
Placental microRNA expression associates with birthweight through control of adipokines: results from two independent cohorts
Epigenetics
placental microrna
placenta
microrna
birthweight
hsa-mir-532-5p
adipokines
leptin
adiponectin
title Placental microRNA expression associates with birthweight through control of adipokines: results from two independent cohorts
title_full Placental microRNA expression associates with birthweight through control of adipokines: results from two independent cohorts
title_fullStr Placental microRNA expression associates with birthweight through control of adipokines: results from two independent cohorts
title_full_unstemmed Placental microRNA expression associates with birthweight through control of adipokines: results from two independent cohorts
title_short Placental microRNA expression associates with birthweight through control of adipokines: results from two independent cohorts
title_sort placental microrna expression associates with birthweight through control of adipokines results from two independent cohorts
topic placental microrna
placenta
microrna
birthweight
hsa-mir-532-5p
adipokines
leptin
adiponectin
url http://dx.doi.org/10.1080/15592294.2020.1827704
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