Placental transcriptome analysis reveals BMI-dependent gene expression profiles in preeclampsia

Maternal obesity is a well-established risk factor for preeclampsia; however, whether increased maternal BMI is associated with biologically distinct subtypes of this disorder remains unknown.

To investigate whether maternal BMI is associated with differences in placental gene expression patterns observed in preeclampsia and to identify transcriptomic signatures with potential relevance for future biomarker research.

This exploratory analysis used placental transcriptomic data obtained from the Gene Expression Omnibus. Differential expression within prespecified contrasts encoding preeclampsia status and maternal BMI was analyzed using a multivariable linear modeling framework with adjustment for relevant confounders. In a secondary analysis, maternal BMI was modeled continuously with an interaction term between BMI and preeclampsia status.

Placental transcriptomic data from 132 placentas representing a range of maternal hypertensive and normotensive states were analyzed. Genes commonly associated with preeclampsia, including FLT1, LEP, HTRA4, and FSTL3, were differentially expressed across all BMI categories. SERPINA3 demonstrated the strongest differential expression in the obese contrast, with an estimated eight-fold increase (95% CI: 3.9-16.6) in preeclamptic pregnancies complicated by obesity, whereas expression differences were smaller and not statistically significant in healthy-weight and overweight contrasts. Gene set enrichment analysis suggested heterogeneity in the underlying biology of preeclampsia across BMI strata.

Placental transcriptional patterns associated with preeclampsia differed across maternal BMI strata. These findings are consistent with previously proposed molecular subtypes of preeclampsia and highlight SERPINA3 as a candidate transcriptomic marker warranting further investigation, specifically in pregnancies complicated by obesity.