Human placental transcriptome shows sexually dimorphic gene expression and responsiveness to maternal dietary n-3 long-chain polyunsaturated fatty acid intervention during pregnancyReport as inadecuate




Human placental transcriptome shows sexually dimorphic gene expression and responsiveness to maternal dietary n-3 long-chain polyunsaturated fatty acid intervention during pregnancy - Download this document for free, or read online. Document in PDF available to download.

BMC Genomics

, 15:941

Human and rodent genomics

Abstract

BackgroundPreviously we have examined the effect of maternal dietary n-3 long-chain polyunsaturated fatty acid LCPUFA supplementation during pregnancy on offspring fat mass. Considering the involvement of the placenta in fetal programming, we aimed to analyze the sex-specific gene expression in human term placenta and its response to the n-3 LCPUFA intervention, as well as their correlations to offspring adiposity.

ResultsPlacental gene expression was assessed in a control and n-3 LCPUFA intervention group by DNA microarrays, biological pathway analyses and RT-qPCR validation. Expression data were correlated with sex steroid hormone levels in placenta and cord plasma, and offspring anthropometric data. Transcriptome data revealed sexually dimorphic gene expression in control placentas per se, whereas in intervention placentas sex-specific expression changed, and more n-3 LCPUFA-regulated genes were found in female than male placentas. Sexually dimorphic gene expression and n-3 LCPUFA-responsive genes were enriched in the pathway for cell cycle and its associated modulator pathways. Significant mRNA expression changes for CDK6, PCNA, and TGFB1 were confirmed by RT-qPCR. CDK6 and PCNA mRNA levels correlated with offspring birth weight and birth weight percentiles. Significantly reduced placental estradiol-17β-testosterone ratio upon intervention found in female offspring correlated with mRNA levels for the -Wnt signaling- genes DVL1 and LRP6.

ConclusionsOverall, human placentas show sexually dimorphic gene expression and responsiveness to maternal n-3 LCPUFA intervention during pregnancy with more pronounced effects in female placentas. The absence of correlations of analyzed placental gene expression with offspring adipose tissue growth in the first year is not mutually exclusive with programming effects, which may manifest later in life, or in other physiological processes.

KeywordsHuman placenta Transcriptome Sexual dimorphism N-3 LCPUFA Pregnancy Fetal programming Sex steroid hormones AbbreviationsConControl group

Con-FFemale offspring in the control group

Con-MMale offspring in the control group

DHADocosahexaenoic acid

E2Estradiol-17beta

EPAEicosapentaenoic acid

INFATI mpact of N utritional F atty Acids during Pregnancy and Lactation on early Human A dipose T issue Development

LCPUFALong-chain polyunsaturated fatty acid

N3N-3 LCPUFA intervention group

N3-FPlacentas of female offspring in the n-3 LCPUFA intervention group

N3-MPlacentas of male offspring in the n-3 LCPUFA intervention group

TTestosterone.

Abbreviations of gene namesACTBβ actin

ANAPC4anaphase promoting complex subunit 4

B2Mβ-2-microglobulin

C8orf59chromosome 8 open reading frame 59

CDK1cyclin-dependent kinase 1

CDK6cyclin-dependent kinase 6

CKS2CDC28 protein kinase regulatory subunit 2

CYP19A1aromatase

DDX3YDEAD Asp-Glu-Ala-Asp box helicase 3, Y-linked

DKK1dickkopf Wnt signaling pathway inhibitor 1

DVL1dishevelled segment polarity protein 1

EIF1AYeukaryotic translation initiation factor 1A, Y-linked

EPS8L2LIMCH EPS8-like 2

FZD7frizzled family receptor 7

HDAC5histone deacetylase 5

HDHD1Ahaloacid dehalogenase-like hydrolase domain containing 1

KDM5Dlysine K-specific demethylase 5D

KDM6Alysine K-specific demethylase 6A

LIMCH1LIM and calponin homology domains 1

LPLlipoprotein lipase

LRP6low density lipoprotein receptor-related protein 6

MAD2L1MAD2 mitotic arrest deficient-like 1

PCNAproliferating cell nuclear antigen

POLR2apolymerase RNA II DNA directed polypeptide A

PPARperoxisome proliferator-activated receptor

RPS4Y1ribosomal protein S4, Y-linked 1

SFRP1secreted frizzled-related protein 1

SSBSjogren syndrome antigen B autoantigen La

STRA6stimulated by retinoic acid 6

TGFB1transforming growth factor beta 1

TOP1topoisomerase DNA I

USP9Yubiquitin specific peptidase 9, Y-linked

UTYubiquitously transcribed tetratricopeptide repeat containing, Y-linked

ZFYzinc finger protein, Y-linked

ZNF711zinc finger protein 711.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2164-15-941 contains supplementary material, which is available to authorized users.

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Author: Eva-Maria Sedlmeier - Stefanie Brunner - Daniela Much - Philipp Pagel - Susanne E Ulbrich - Heinrich HD Meyer - Ulrike Am

Source: https://link.springer.com/







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