Early Origins of Adult Health Research Group, Health and Biomedical Innovation, UniSA: Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, Australia.
Mater Medical Research Institute, The University of Queensland, Brisbane, QLD 4101, Australia.
Int J Mol Sci. 2024 Jan 30;25(3):1688. doi: 10.3390/ijms25031688.
A birthweight centile (BWC) below the 25th is associated with an elevated risk of adverse perinatal outcomes, particularly among males. This male vulnerability may stem from alterations in placenta-specific androgen signalling, a signalling axis that involves the androgen receptor (AR)-mediated regulation of target genes containing androgen response elements (AREs). In this study, we examined global and ARE-specific transcriptomic signatures in term male placentae (≥37 weeks of gestation) across BWC subcategories (<10th, 10th-30th, >30th) using RNA-seq and gene set enrichment analysis. ARE-containing transcripts in placentae with BWCs below the 10th percentile were upregulated compared to those in the 10th-30th and >30th percentiles, which coincided with the enrichment of gene sets related to hypoxia and the suppression of gene sets associated with mitochondrial function. In the absence of ARE-containing transcripts in silico, <10th and 10th-30th BWC subcategory placentae upregulated gene sets involved in vasculature development, immune function, and cell adhesion when compared to those in the >30th BWC subcategory. Collectively, our in silico findings suggest that changes in the expression of ARE-containing transcripts in male placentae may contribute to impaired placental vasculature and therefore result in reduced fetal growth outcomes.
体重百分位数（BWC）低于第 25 个百分位数与围产期不良结局的风险升高有关，尤其是在男性中。这种男性脆弱性可能源于胎盘特异性雄激素信号的改变，这是一个涉及雄激素受体（AR）介导的含有雄激素反应元件（AREs）的靶基因调节的信号轴。在这项研究中，我们使用 RNA-seq 和基因集富集分析，检查了整个男性胎盘（≥37 周妊娠）和 BWC 亚类（<10 个百分位数，10-30 个百分位数，>30 个百分位数）的全球和 ARE 特异性转录组特征。与第 10-30 个和>30 个百分位数相比，BWCs 低于第 10 个百分位数的胎盘中的 ARE 转录物上调，这与与缺氧相关的基因集的富集和与线粒体功能相关的基因集的抑制一致。在不存在含有 ARE 的转录物的情况下，与>30 个 BWC 亚类相比，<10 个和 10-30 个 BWC 亚类的胎盘上调了与血管发育、免疫功能和细胞黏附相关的基因集。总的来说，我们的计算机发现表明，男性胎盘中含有 ARE 的转录物表达的变化可能导致胎盘血管受损，从而导致胎儿生长结局不良。
