在整个妊娠期内,人类胎盘中循环化物代谢的表征
Ashley S Meakin1, Kathryn L Gatford2, Yu-Chin Lien3
1Early Origins of Adult Health Research Group, Health and Biomedical Innovation, Clinical & Health Sciences, University of South Australia, Adelaide, SA, Australia.
人类胎盘将前药物环胺 (CIC) 转化为其活性形式des-CIC. 这种胎盘转换可能会限制CIC.
科学领域:
- 生殖生物学和药理学生殖生物学和药理学
- 孕产妇和胎儿的医学
- 药物代谢和药物的发展.
背景情况:
- 产前皮质类固醇 (ACS) 治疗使胎儿肺部成熟,但可能会损害大脑发育.
- 需要新的治疗方法来避免不良的神经发育影响.
- 西克莱索尼德 (CIC) 是一种前药物,在由特定酶转化为des-CIC后激活葡萄糖皮质体受体 (GR).
研究的目的:
- 在整个妊娠期内调查人类胎盘中碳酸酶 (CES) 基因表达.
- 为了确定CIC转化为其活性形式,des-CIC,在胎盘组织.
- 评估胎盘的潜力,以调解胎儿暴露在活性GR激动剂中的潜力.
主要方法:
- 使用DESeq2对第二个三个月的胎盘样本中ACHE和CES1/2的基因表达差异分析,早产和分娩使用DESeq2.
- 功能性检测测量CIC转化为des-CIC在胎盘扩张的测量.
- 基因表达和转化活动在不同妊娠年龄和性别之间的比较.
主要成果:
- 乙胆化酶 (ACHE) 的mRNA表达在第二个三个月的男性胎盘中高于早产和满产的男性.
- 在第二个三个月的胎盘中,Carboxylesterase 1 (CES1) mRNA表达显著高于两个性别的早产或终产胎盘.
- 由胎盘组织将CIC转换为des-CIC,与妊娠年龄没有显著变化.
结论:
- 人类胎盘拥有能够将CIC转化为des-CIC的酶机制.
- 这种胎盘转化可能会限制活跃的GR激动剂的向性全身输送,用于威胁过早分娩.
- 需要进一步的体内研究来量化胎盘激活及其对胎儿暴露的影响.
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