第一孕期末人类胎盘转录组的性别差异。

Sex differences in the late first trimester human placenta transcriptome.

机构信息

Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.

出版信息

Biol Sex Differ. 2018 Jan 15;9(1):4. doi: 10.1186/s13293-018-0165-y.

DOI:10.1186/s13293-018-0165-y

PMID:29335024

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5769539/

Abstract

BACKGROUND

Development 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.

METHODS

RNA-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.

RESULTS

RNA-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.

CONCLUSIONS

This 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.

摘要

背景

在妊娠早期的最后阶段，胎盘的发育对于确保胎儿的正常生长和发育至关重要。此窗口期的发育差异，如性别特异性变异，与后来的胎盘疾病状态有关，但此时的基因表达却知之甚少。

方法

对经过基因检测的 39 例妊娠早期绒毛膜（17 例女性，22 例男性）进行 RNA 测序，以描述其转录组。进行基因富集分析，以寻找在妊娠早期富集的经典途径和基因本体论。使用 DESeq2 寻找性别二态性基因表达。分析绒毛取样和出生时胎儿体重的患者人口统计学数据，以发现性别差异。

结果

RNA 测序分析检测到 14250 个表达基因，其中 19 号染色体贡献最大（973/2852，19 号染色体基因的 34.1%），Y 染色体贡献最小（16/568，Y 染色体基因的 2.8%）。鉴定出一些胎盘特异性基因以及组蛋白编码基因，它们在妊娠早期是特有的，且在两性中都是共同的。此外，我们发现了 58 个在男性和女性之间表达差异显著的基因：25 个 X 连锁基因，15 个 Y 连锁基因，18 个常染色体基因。X 连锁基因中上调的基因中有 59.1%是 X 染色体失活逃避基因。许多因性别而表达不同的基因包含 X/Y 基因对，这表明剂量补偿在性别差异中发挥作用。这些 X/Y 对在并行的、对真核细胞生长和存活至关重要的古老经典途径中具有作用：染色质修饰、转录、剪接和翻译。

结论

本研究首次对妊娠早期最后阶段胎盘转录组进行了描述，强调了在继续妊娠并导致活产的两性之间的相似性和差异性。性二态性可能会导致妊娠结局，包括胎儿生长和出生体重，这在我们的队列中得到了体现，男性出生时比女性重。该转录组为开发胎盘功能的早期诊断测试提供了基础，这些测试可以指示整体妊娠健康、胎儿-母体健康和长期成人健康。