School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Queensland, 4001, Australia.
Pregnancy and Development Group, Mater Research, Translational Research Institute and the University of Queensland, Brisbane, Queensland, 4101, Australia.
Placenta. 2022 Oct;128:1-8. doi: 10.1016/j.placenta.2022.08.004. Epub 2022 Aug 18.
The pathological decrease of fetal growth during gestation can lead to subsequent poor health outcomes for the fetus. This process is commonly controlled by the placenta, the interface between mother and baby during gestation. Sex-specific gene expression has been implicated in placental function, therefore, there is a need to determine if it is important during reduced fetal growth. We therefore aimed to characterise placental gene expression at term to evaluate sex-specific genetic changes that occur in small for gestational age (SGA) infants.
RNA-sequencing of twelve human placental tissue samples collected from pregnancies yielding either term appropriate for gestational age (AGA) or SGA infants identified at delivery. Candidate genes associated with fetal size and fetal sex were identified using differential gene expression and weighted gene co-expression network analyses. Single-cell sequencing data was used for candidate validation and to estimate candidate transcript expression in specific placental cell populations.
Differential gene expression and weighted gene co-expression network analyses identified 403 candidate transcripts associated with SGA infants. One hundred and three of these transcripts showed sex-specific expression. . Published placental sequencing datasets were used to validate the key expression results from the twelve placental samples initially studied; the sex-independent transcript expression for genes involved in cell cycle processes in males (7 transcripts) and endoplasmic reticulum stress in females (17 transcripts).
This study identified the activation of multiple molecular mechanisms involved in the placental response to an adverse environmental stressor. Mechanisms such as disrupted protein synthesis were shared between infant biological sex when comparing AGA to SGA, whilst other pathways such as cell cycle and endoplasmic reticulum stress appear as independent/specific to either males or females when investigating reduced fetal growth. This data suggests that sexual dimorphism is an important consideration when examining placental dysfunction and poor fetal growth.
妊娠期间胎儿生长的病理性下降会导致胎儿随后出现健康不良结局。这一过程通常受到胎盘的控制，胎盘是妊娠期间母体和胎儿之间的界面。性别特异性基因表达与胎盘功能有关，因此，有必要确定其在胎儿生长受限中是否重要。因此，我们旨在对足月胎盘基因表达进行特征描述，以评估在小于胎龄儿（SGA）婴儿中发生的性别特异性遗传变化。
对 12 例分娩时发现的足月适宜胎龄（AGA）或 SGA 婴儿的胎盘组织样本进行 RNA 测序，以识别候选基因。使用差异基因表达和加权基因共表达网络分析，鉴定与胎儿大小和胎儿性别相关的候选基因。单细胞测序数据用于候选验证，并估计候选转录物在特定胎盘细胞群中的表达。
差异基因表达和加权基因共表达网络分析确定了 403 个与 SGA 婴儿相关的候选转录物。其中 103 个转录物表现出性别特异性表达。利用已发表的胎盘测序数据集对最初研究的 12 个胎盘样本的关键表达结果进行了验证；在比较 AGA 与 SGA 时，涉及男性细胞周期过程（7 个转录物）和女性内质网应激（17 个转录物）的基因的性别独立性转录物表达。
本研究鉴定了多种与胎盘对不利环境应激反应相关的分子机制的激活。在比较 AGA 与 SGA 时，如蛋白质合成中断等机制在婴儿的生物性别之间是共享的，而在研究胎儿生长受限时，细胞周期和内质网应激等其他途径似乎是独立于男性或女性的。这些数据表明，在检查胎盘功能障碍和胎儿生长不良时，性别二态性是一个重要的考虑因素。
