(362) Variable Expression of sFlt-1 Splice Variants in Distinct Placental Cells in Normal and Preeclamptic Pregnancies

Objective:




Elevated levels of soluble fms-like tyrosine kinase-1 (sFlt-1) have been associated with placental disorders, such as preeclampsia. However, the precise expression patterns and regulation of the main placental sFlt1 splice variants, e15a and i13, within the intricate placental tissue remain poorly understood. The aim of our study is to investigate how these splice variants are differentially expressed and regulated across pregnancy and in preeclampsia, providing insights into their roles in placental pathology.


Study Design: We used 16 placental samples for this study. First-trimester samples were obtained from women undergoing pregnancy terminations, while samples from individuals with preeclampsia and gestational age-matched controls were collected at the time of delivery. Cellular localization of sFlt-1 e15a and sFlt-1 i13 transcripts was analyzed by RNA in situ hybridization using a custom-designed BaseScope probe for e15a and a 35S-labeled probe for i13.

Results: In the first-trimester placentas, e15a and i13 mRNAs were highly expressed in the intermediate trophoblasts and invading cytotrophoblast columns. In term placentas (controls), the signal was primarily detected in the extravillous trophoblasts located in the basal plate/decidua. In preeclamptic placentas, the expression of both e15a and i13 was markedly elevated in the extravillous trophoblasts and also observed in some villi near the basal plate. Notably, the signals for both e15a and i13 were highly focal within the villi but more widespread in the extravillous trophoblasts. Furthermore, the e15a signal was stronger in the villi, while the i13 signal was more intense in the extravillous trophoblasts.

Conclusion:
Our findings reveal that sFlt-1 e15a and i13 expression in the placenta is highly localized and confined to specific cell types, challenging the previous notion of their widespread and uniform distribution. This localized expression highlights the importance of understanding the cell-specific regulatory mechanisms of sFlt-1 in unraveling the pathophysiology of pregnancy complications.