Sex differences in the late first trimester human placenta transcriptome

Abstract

BackgroundDevelopment of the placenta during the late first trimester is critical to ensure normal growth and development of the fetus. Developmental differences in this window such as sex-specific variation are implicated in later placental disease states, yet gene expression at this time is poorly understood.MethodsRNA-sequencing was performed to characterize the transcriptome of 39 first trimester human placentas using chorionic villi following genetic testing (17 females, 22 males). Gene enrichment analysis was performed to find enriched canonical pathways and gene ontologies in the first trimester. DESeq2 was used to find sexually dimorphic gene expression. Patient demographics were analyzed for sex differences in fetal weight at time of chorionic villus sampling and birth.ResultsRNA-sequencing analyses detected 14,250 expressed genes, with chromosome 19 contributing the greatest proportion (973/2852, 34.1% of chromosome 19 genes) and Y chromosome contributing the least (16/568, 2.8%). Several placenta-enriched genes as well as histone-coding genes were identified to be unique to the first trimester and common to both sexes. Further, we identified 58 genes with significantly different expression between males and females: 25 X-linked, 15 Y-linked, and 18 autosomal genes. Genes that escape X inactivation were highly represented (59.1%) among X-linked genes upregulated in females. Many genes differentially expressed by sex consisted of X/Y gene pairs, suggesting that dosage compensation plays a role in sex differences. These X/Y pairs had roles in parallel, ancient canonical pathways important for eukaryotic cell growth and survival: chromatin modification, transcription, splicing, and translation.ConclusionsThis study is the first characterization of the late first trimester placenta transcriptome, highlighting similarities and differences among the sexes in ongoing human pregnancies resulting in live births. Sexual dimorphism may contribute to pregnancy outcomes, including fetal growth and birth weight, which was seen in our cohort, with males significantly heavier than females at birth. This transcriptome provides a basis for development of early diagnostic tests of placental function that can indicate overall pregnancy heath, fetal-maternal health, and long-term adult health.Electronic supplementary materialThe online version of this article (10.1186/s13293-018-0165-y) contains supplementary material, which is available to authorized users.

Preliminary RNA-Seq Analysis of Long Non-Coding RNAs Expressed in Human Term Placenta

“…According to the current data, 4463 known and 990 previously unknown (predicted) lncRNAs are expressed in human term placental tissue ( Figure 1 ). In comparison, RNA-Seq analysis of first-trimester human placenta transcriptome revealed transcript biotypes in the following classes: 77% protein-coding genes, 9.8% long non-coding genes, and 6.5% pseudogenes [ 31 ]. However, the current analysis allowed identification of 21 genes with significantly different expression between males and females, compared to 58 genes discovered by Gonzalez et al [ 31 ].…”

Blastocyst transfer in mice alters the placental transcriptome and growth

“…A genomewide transcriptome analysis was performed via RNA sequencing to determine differential mRNA expression in whole placentas from control (n = 4) or transferred (n = 4) C57Bl/6 conceptuses at E10.5. Since the placenta transcriptome is known to exhibit some sexual dimorphism (Gonzalez et al 2018) and due to tissue availability, only male placentas associated with PN embryos were selected for analysis. cDNA libraries generated from placental RNA were sequenced using the NextSeq500 (Illumina) platform and bioinformatically analysed.…”

Impacts of bisphenol A (BPA) and phthalate exposures on epigenetic outcomes in the human placenta

“…The placenta undergoes sex-specific development [ 98–100 ], which likely explains the observed sexually dimorphic placental responses to a variety of maternal factors, including diet [ 101–103 ], obesity [ 104 ], and stress [ 105 , 106 ]. It is especially critical to consider placental sex when assessing the impact of external stressors on epigenetic endpoints, as there is evidence to suggest that associations between placental epigenetic markers and fetal outcomes may be sex-specific [ 107–109 ].…”