两个出生队列中胎盘长链非编码RNA表达与孕妇孕前体重指数及婴儿出生体重的关联
Associations of placental lncRNA expression with maternal pre-pregnancy BMI and infant birthweight in two birth cohorts.
作者信息
Hussey Michael R, MacDonald James, Bammler Theo K, Tekola-Ayele Fasil, Kerr Kathleen F, Paquette Alison G, Marsit Carmen J, LeWinn Kaja Z, Zhao Qi, Karr Catherine J, Sathyanarayana Sheela, Enquobahrie Daniel A
机构信息
Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA.
Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, Seattle, WA, USA.
出版信息
J Dev Orig Health Dis. 2025 May 21;16:e20. doi: 10.1017/S204017442500011X.
Pre-pregnancy obesity (ppOB) is linked to pregnancy complications and abnormal fetal growth through placental mechanisms, and long non-coding RNAs (lncRNAs) may play an epigenetic role in these processes. We investigated overall and sex-specific associations of pre-pregnancy body mass index (ppBMI), ppOB, and birthweight with placental lncRNA transcripts in two birth cohorts. Study participants were mother-child dyads recruited to the CANDLE (Memphis, TN)( = 725) and GAPPS (Seattle and Yakima, WA)( = 159) cohorts. Maternal ppBMI was assessed at enrollment using interviewer-administered questionnaires. LncRNAs (1,077 and 1,033 for CANDLE and GAPPS, respectively) were sequenced from placental samples collected at birth. Placental lncRNA was regressed on ppBMI, ppOB (ppBMI ≥30kg/m), or continuous birthweight in cohort-specific weighted linear models controlling for -specified confounders and experimental variables. Potential effect modification by infant-sex was examined in sex-stratified analyses and models including BMI-infant-sex interaction terms. No lncRNA transcripts were significantly associated with ppBMI, ppOB, or birthweight in primary models. Among male infants in CANDLE, expression of three lncRNA transcripts (, , ) was associated with ppBMI and one transcript () with birthweight. In GAPPS, ppBMI was associated with two lncRNA transcripts ( and ) among males, and birthweight was associated with 17 lncRNA transcripts (including , , and ) among females. No BMI-infant-sex interactions were observed. Though many of these potential associations are for uncharacterized transcripts, several identified lncRNAs (e.g., and ) have been linked to pathways controlling cancer or placental growth, trophoblast differentiation, and gene expression. These associations warrant validation in future studies.
孕前肥胖(ppOB)通过胎盘机制与妊娠并发症和胎儿生长异常相关,长链非编码RNA(lncRNAs)可能在这些过程中发挥表观遗传作用。我们在两个出生队列中研究了孕前体重指数(ppBMI)、ppOB和出生体重与胎盘lncRNA转录本的总体及性别特异性关联。研究参与者为招募到CANDLE(田纳西州孟菲斯)(n = 725)和GAPPS(华盛顿州西雅图和亚基马)(n = 159)队列中的母婴二元组。使用访员管理的问卷在入组时评估孕妇的ppBMI。分别从出生时采集的胎盘样本中对lncRNAs(CANDLE和GAPPS分别为1077个和1033个)进行测序。在控制特定混杂因素和实验变量的队列特异性加权线性模型中,将胎盘lncRNA与ppBMI、ppOB(ppBMI≥30kg/m²)或连续出生体重进行回归分析。在按性别分层的分析和包括BMI-婴儿性别交互项的模型中检验婴儿性别的潜在效应修饰作用。在主要模型中,没有lncRNA转录本与ppBMI、ppOB或出生体重显著相关。在CANDLE队列的男婴中,三种lncRNA转录本(......)的表达与ppBMI相关,一种转录本(......)与出生体重相关。在GAPPS队列中,ppBMI与男性中的两种lncRNA转录本(......和......)相关,出生体重与女性中的17种lncRNA转录本(包括......、......和......)相关。未观察到BMI-婴儿性别交互作用。尽管这些潜在关联中的许多是针对未表征的转录本,但一些已鉴定的lncRNAs(例如......和......)已与控制癌症或胎盘生长、滋养层分化和基因表达的途径相关联。这些关联有待未来研究进行验证。