Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Expression of the placental transcriptome in fetal growth restriction in the Baboon is Dependent on Fetal Sex

ABSTRACT: Fetal growth restriction (FGR) develops when fetal nutrient availability is compromised and increases the risk for perinatal complications and predisposes for offspring obesity, diabetes and cardiovascular disease later in life. Emerging evidence implicates changes in placental function in altered fetal growth and the subsequent development of adult disease. The susceptibility for disease in response to an adverse intrauterine environment differs distinctly between boys and girls, with girls typically having better outcomes. Here, we test the hypothesis that regulation of the placental transcriptome by moderate nutrient reduction is dependent on fetal sex. We used a non-human primate model of FGR in which maternal global food intake is reduced by 30% starting at gestational day (GD) 30. At GD 165 (term = GD 183) placental genome expression profiling was carried out followed by bioinformatics including pathway and network analysis. Surprisingly, there was no coordinated placental molecular response to decreased nutrient availability when analyzing the data without accounting for fetal sex. In contrast, female placentas exhibited a highly coordinated response that included up-regulation of genes in networks, pathways and functional groups related to programmed cell death and down-regulation of genes in networks, pathways and functional groups associated with cell proliferation. These changes were not apparent in the male placentas. Our data support the concept that female placentas initiate complex adaptive responses to an adverse intrauterine environment, which may contribute to increased survival and better pregnancy outcomes in girls. Total RNA obtained from 165dGA control female (n=3), control male (n=3), nutrient restricted female (n=3), and nutrient restricted male (n=3) pregnancies.

ORGANISM(S): Papio hamadryas

SUBMITTER: Laura Cox

PROVIDER: E-GEOD-40878 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Expression of the placental transcriptome in maternal nutrient reduction in baboons is dependent on fetal sex.

Cox Laura A LA Li Cun C Glenn Jeremy P JP Lange Kenneth K Spradling Kimberly D KD Nathanielsz Peter W PW Jansson Thomas T

The Journal of nutrition 20130918 11

Maternal undernutrition increases the risk of perinatal complications and predisposes offspring to obesity, diabetes, and cardiovascular disease later in life. Emerging evidence suggests that changes in placental function play a role in linking altered maternal nutrition in pregnancy to the subsequent development of adult disease. The susceptibility for disease in response to an adverse intrauterine environment differs distinctly between boys and girls, with girls typically having better outcome ...[more]

PMID: 24047701

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Project description:Worldwide, fetal growth restriction (FGR) affects 7 to 10% of pregnancies, or roughly 20.5 million infants, each year. FGR not only increases neonatal mortality and morbidity but also the risk of obesity in later life. Currently, the molecular mechanisms by which FGR "programs" an obese phenotype are not well understood. Studies demonstrate that FGR females are more prone to obesity compared to males; however, the molecular mechanisms that lead to the sexually dimorphic programming of FGR are not known. Thus, we hypothesized that FGR leads to the sexually dimorphic programming of preadipocytes and reduces their ability to differentiate into mature adipocytes. To test the hypothesis, we utilized a maternal hyperthermia-induced placental insufficiency to restrict fetal growth in sheep. We collected perirenal adipose tissue from male and female near-term FGR and normal-weight fetal lambs (N=4 in each group, 16 total), examined the preadipocytes' differentiation potential, and identified differential mRNA transcript expression in perirenal adipose tissue. Male FGR fetuses have lower cellular density compared to control male fetuses. However, no difference was observed in female FGR fetuses compared to control female fetuses. In addition, the ability of preadipocytes to differentiate into mature adipocytes with fat accumulation was impaired in male FGR fetuses, but this was not observed in female FGR fetuses. Finally, we examined the genes and pathways involved in the sexually dimorphic programming of obesity by FGR. On enrichment of differentially expressed genes in males compared to females, the Thermogenesis KEGG Pathway was downregulated, and the Metabolic and Steroid Biosynthesis KEGG pathways were upregulated. On enrichment of differentially expressed genes in male FGR compared to male control, the Steroid Biosynthesis KEGG Pathway was downregulated, and the PPAR Signaling KEGG pathway was upregulated. No pathways were altered in females in response to growth restriction in perirenal adipose tissue. Thus, the present study demonstrates a sexually dimorphic program in response to growth restriction in sheep fetal perirenal adipose tissue.

Dataset Information

Expression of the placental transcriptome in fetal growth restriction in the Baboon is Dependent on Fetal Sex

Publications

Expression of the placental transcriptome in maternal nutrient reduction in baboons is dependent on fetal sex.

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