PDF(Pubmed)
Abstract：
Fetal sex affects fetal and maternal health outcomes in pregnancy, but this connection remains poorly understood. As the placenta is the route of fetomaternal communication and derives from the fetal genome, placental gene expression sex differences may explain these outcomes.
We utilized next generation sequencing to study the normal human placenta in both sexes in first and third trimester to generate a normative transcriptome based on sex and gestation.
We analyzed 124 first trimester (T1, 59 female and 65 male) and 43 third trimester (T3, 18 female and 25 male) samples for sex differences within each trimester and sex-specific gestational differences.
Placenta shows more significant sexual dimorphism in T1, with 94 T1 and 26 T3 differentially expressed genes (DEGs). The sex chromosomes contributed 60.6% of DEGs in T1 and 80.8% of DEGs in T3, excluding X/Y pseudoautosomal regions. There were 6 DEGs from the pseudoautosomal regions, only significant in T1 and all upregulated in males. The distribution of DEGs on the X chromosome suggests genes on Xp (the short arm) may be particularly important in placental sex differences. Dosage compensation analysis of X/Y homolog genes shows expression is primarily contributed by the X chromosome. In sex-specific analyses of first versus third trimester, there were 2815 DEGs common to both sexes upregulated in T1, and 3263 common DEGs upregulated in T3. There were 7 female-exclusive DEGs upregulated in T1, 15 female-exclusive DEGs upregulated in T3, 10 male-exclusive DEGs upregulated in T1, and 20 male-exclusive DEGs upregulated in T3.
This is the largest cohort of placentas across gestation from healthy pregnancies defining the normative sex dimorphic gene expression and sex common, sex specific and sex exclusive gene expression across gestation. The first trimester has the most sexually dimorphic transcripts, and the majority were upregulated in females compared to males in both trimesters. The short arm of the X chromosome and the pseudoautosomal region is particularly critical in defining sex differences in the first trimester placenta. As pregnancy is a dynamic state, sex specific DEGs across gestation may contribute to sex dimorphic changes in overall outcomes.
We utilized next generation sequencing to study the normal human placenta in both sexes in first and third trimester to generate a normative transcriptome based on sex and gestation.
We analyzed 124 first trimester (T1, 59 female and 65 male) and 43 third trimester (T3, 18 female and 25 male) samples for sex differences within each trimester and sex-specific gestational differences.
Placenta shows more significant sexual dimorphism in T1, with 94 T1 and 26 T3 differentially expressed genes (DEGs). The sex chromosomes contributed 60.6% of DEGs in T1 and 80.8% of DEGs in T3, excluding X/Y pseudoautosomal regions. There were 6 DEGs from the pseudoautosomal regions, only significant in T1 and all upregulated in males. The distribution of DEGs on the X chromosome suggests genes on Xp (the short arm) may be particularly important in placental sex differences. Dosage compensation analysis of X/Y homolog genes shows expression is primarily contributed by the X chromosome. In sex-specific analyses of first versus third trimester, there were 2815 DEGs common to both sexes upregulated in T1, and 3263 common DEGs upregulated in T3. There were 7 female-exclusive DEGs upregulated in T1, 15 female-exclusive DEGs upregulated in T3, 10 male-exclusive DEGs upregulated in T1, and 20 male-exclusive DEGs upregulated in T3.
This is the largest cohort of placentas across gestation from healthy pregnancies defining the normative sex dimorphic gene expression and sex common, sex specific and sex exclusive gene expression across gestation. The first trimester has the most sexually dimorphic transcripts, and the majority were upregulated in females compared to males in both trimesters. The short arm of the X chromosome and the pseudoautosomal region is particularly critical in defining sex differences in the first trimester placenta. As pregnancy is a dynamic state, sex specific DEGs across gestation may contribute to sex dimorphic changes in overall outcomes.
摘要：
背景：胎儿性别影响妊娠期间胎儿和产妇的健康结局，但是这种联系仍然知之甚少。由于胎盘是胎儿交流的途径，来源于胎儿基因组，胎盘基因表达的性别差异可能解释了这些结果。
目的：我们利用下一代测序技术来研究孕早期和孕晚期两种性别的正常人胎盘，以产生基于性别和妊娠的规范转录组。
方法：我们分析了124个孕早期（T1，59名女性和65名男性）和43个孕晚期（T3，18名女性和25名男性）样本在每个孕期的性别差异和性别特异性妊娠差异。
结果：胎盘在T1表现出更明显的性二态性，有94个T1和26个T3差异表达基因（DEGs）。性染色体在T1中占DEGs的60.6％，在T3中占DEGs的80.8％，不包括X/Y伪常染色体区域。有6个来自伪常染色体区域的DEGs，仅在T1中显着，在男性中均上调。DEGs在X染色体上的分布表明Xp（短臂）上的基因在胎盘性别差异中可能特别重要。X/Y同源基因的剂量补偿分析显示表达主要由X染色体贡献。在妊娠早期和晚期的性别特异性分析中，在T1中，男女共有2815个DEG上调，在T3中3263个普通DEG上调。T1有7个女性专属DEG上调，T3有15个女性专属DEG上调，T1有10个男性专属DEG上调，T3有20个男性专属DEG上调。
结论：这是从健康妊娠开始的最大的胎盘队列，定义了规范的性别双态基因表达和性别共同，跨妊娠的性别特异性和性别专有基因表达。孕早期有最多的性二态笔录，在两个三个月中，与男性相比，女性中的大多数人都被上调。X染色体的短臂和伪常染色体区域在确定妊娠早期胎盘的性别差异方面尤为重要。由于怀孕是一个动态的状态，妊娠期性别特异性DEGs可能导致总体结局的性别二态变化.
目的：我们利用下一代测序技术来研究孕早期和孕晚期两种性别的正常人胎盘，以产生基于性别和妊娠的规范转录组。
方法：我们分析了124个孕早期（T1，59名女性和65名男性）和43个孕晚期（T3，18名女性和25名男性）样本在每个孕期的性别差异和性别特异性妊娠差异。
结果：胎盘在T1表现出更明显的性二态性，有94个T1和26个T3差异表达基因（DEGs）。性染色体在T1中占DEGs的60.6％，在T3中占DEGs的80.8％，不包括X/Y伪常染色体区域。有6个来自伪常染色体区域的DEGs，仅在T1中显着，在男性中均上调。DEGs在X染色体上的分布表明Xp（短臂）上的基因在胎盘性别差异中可能特别重要。X/Y同源基因的剂量补偿分析显示表达主要由X染色体贡献。在妊娠早期和晚期的性别特异性分析中，在T1中，男女共有2815个DEG上调，在T3中3263个普通DEG上调。T1有7个女性专属DEG上调，T3有15个女性专属DEG上调，T1有10个男性专属DEG上调，T3有20个男性专属DEG上调。
结论：这是从健康妊娠开始的最大的胎盘队列，定义了规范的性别双态基因表达和性别共同，跨妊娠的性别特异性和性别专有基因表达。孕早期有最多的性二态笔录，在两个三个月中，与男性相比，女性中的大多数人都被上调。X染色体的短臂和伪常染色体区域在确定妊娠早期胎盘的性别差异方面尤为重要。由于怀孕是一个动态的状态，妊娠期性别特异性DEGs可能导致总体结局的性别二态变化.
