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

被引:55
作者
Sedlmeier, Eva-Maria [1 ,2 ,6 ]
Brunner, Stefanie [3 ]
Much, Daniela [3 ]
Pagel, Philipp [4 ]
Ulbrich, Susanne E. [5 ]
Meyer, Heinrich H. D. [5 ]
Amann-Gassner, Ulrike [3 ]
Hauner, Hans [2 ,3 ,6 ]
Bader, Bernhard L. [1 ,2 ,6 ]
机构
[1] Tech Univ Munich, Res Ctr Nutr & Food Sci ZIEL, ZIEL PhD Grad Sch Epigenet Imprinting & Nutr, Freising Weihenstephan, Germany
[2] Tech Univ Munich, Else Kroner Fresenius Ctr Nutr Med, Freising Weihenstephan, Germany
[3] Tech Univ Munich, Klinikum Rechts Isar, Else Kroner Fresenius Ctr Nutr Med, D-80290 Munich, Germany
[4] Tech Univ Munich, Chair Genome Oriented Bioinformat, Freising Weihenstephan, Germany
[5] Tech Univ Munich, Res Ctr Nutr & Food Sci ZIEL, Physiol Unit, Freising Weihenstephan, Germany
[6] Tech Univ Munich, Res Ctr Nutr & Food Sci ZIEL, Clin Nutr Med Unit, D-85350 Freising Weihenstephan, Germany
关键词
Human placenta; Transcriptome; Sexual dimorphism; N-3; LCPUFA; Pregnancy; Fetal programming; Sex steroid hormones; ADIPOSE-TISSUE DEVELOPMENT; DOCOSAHEXAENOIC ACID; ENZYME-IMMUNOASSAY; FISH-OIL; TESTOSTERONE PRODUCTION; STEROID CONCENTRATIONS; VILLOUS TROPHOBLAST; X-INACTIVATION; FETAL SEX; GROWTH;
D O I
10.1186/1471-2164-15-941
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Background: Previously 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. Results: Placental 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-17 beta/testosterone ratio upon intervention found in female offspring correlated with mRNA levels for the 'Wnt signaling' genes DVL1 and LRP6. Conclusions: Overall, 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.
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页数:19
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