Characterization of senescence-associated transcripts in the human placenta

Area of Science:

• Obstetrics and Gynecology
• Cellular Biology
• Genomics

Background:

• Trophoblast senescence is linked to obstetrical syndromes such as preeclampsia and fetal growth restriction (FGR).
• A specific set of 28 senescence-associated secretory phenotype (SASP) transcripts has been identified in preeclamptic placentas.

Purpose of the Study:

• To investigate the regulation of a defined set of placental senescence-associated secretory phenotype (SASP) transcripts.
• To determine if these SASP transcripts are uniquely regulated in late-term placentas or in placentas from pregnancies with major obstetrical syndromes.

Main Methods:

• Analysis of placental RNA sequencing data from healthy and diseased pregnancies (preeclampsia, FGR, FGR with hypertensive disorder, preterm delivery).
• Comparison of SASP transcript expression between preterm (<37 weeks) and late-term (≥41 weeks) deliveries.
• In vitro assessment of SASP expression in primary human trophoblasts under conditions of hypoxia, reduced differentiation, or apoptosis/ferroptosis.

Main Results:

• Eight of 28 SASP transcripts showed significant changes between preterm and late-term deliveries, with specific genes upregulated (FSTL3, IL1RL1, INHBA, VEGFA) and others downregulated (STC1, RARRES2, MRC2, SELP).
• SASP mRNA expression was notably enriched in placentas from FGR/hypertensive disorder pregnancies.
• In vitro studies linked hypoxia and apoptosis to altered expression of FSTL3, VEGFA, and DKK1.

Conclusions:

• A distinct set of placental SASPs characterizes late-term placentas and placental dysfunction syndromes.
• Trophoblastic SASP signatures show potential for characterizing placental senescence in both normal and pathological pregnancies.