| Popis: |
Preeclampsia is a serious pregnancy disorder that is thought to result from the dysregulation of placental function and can be detrimental to both the mother and developing fetus. Preeclampsia impacts up to 8% of all pregnancies worldwide, yet the factors contributing to the development of this disease remain largely unknown. This study set out to test the hypothesis that understudied xenobiotic chemicals are capable of reaching the human placenta and disrupting critical pathways relevant to placental cell health and preeclampsia. Placentas from a previously established cohort of patients with normotensive and preeclamptic pregnancies were analyzed using non-targeted approaches to identify unknown molecular features. A total of 29 molecular features that represent 27 unique chemicals were statistically associated with preeclampsia disease status. One of the identified chemicals showing the largest increase in concentration was acetaminophen. Concentrations of acetaminophen were found to be associated with altered expression of 27 genes and 57 miRNAs and altered methylation status of 18 genes relevant to preeclampsia among the same samples. Acetaminophen-associated genes showed enrichment for cell compromise and death-related signaling, which were further characterized through in vitro testing with immortalized trophoblasts. This research provides novel evidence towards characterizing chemicals in the placental and identified APAP as one of the most significantly associated compounds related to preeclampsia. Mechanistic findings showed changes in signaling relevant to placental cell damage and death that may be relevant to preeclampsia etiology and support the need for further investigation. |
