Medicine› Obstetrics and Gynecology› Pregnancy and preeclampsia studies

Fetal growth restriction — Prenatal sildenafil and fetal-placental cardiorenal programming

Submitted 2026-10-22

Field: Medicine › Obstetrics and GynecologyType: No effect foundArea: fetal growth restrictionTarget: Prenatal sildenafil and fetal-placental cardiorenal programmingStage: randomized trial

Hypothesis

Sildenafil given during pregnancies complicated by severe early-onset fetal growth restriction would change fetal-placental gene programming related to cardiovascular and renal development.

What failed

Whole-genome RNA sequencing of umbilical vein endothelial cells (12 sildenafil, 8 placebo) and placentas (13 per group) from the Dutch STRIDER trial showed similar expression profiles between groups; sildenafil did not change cardiovascular or renal programming.

Broken assumption

Prenatal sildenafil reprogrammes the cardiovascular and renal development of growth-restricted fetuses.

Why

A few placental gene sets involved in the nitric oxide pathway were altered, which the authors read as reflecting sildenafil's mechanism of action, along with upregulated immune-pathway gene sets — but no reprogramming of cardiorenal health.

From the published paper: Terstappen et al. Journal of Trial and Error, 2023. ↗CC BY

Research ideas from this failure

Unvetted lead — read the papers

New hypotheses this failure suggests, each with a crucial experiment, a rival explanation of the original result, and the papers it rests on. Written by AI from paper titles and abstracts found on OpenAlex (and Europe PMC, for life and health sciences).

Related failures (1)

Matched on shared genes, mechanisms and ways of failing as well as wording. Each shows why it matched — treat these as leads rather than verdicts.

vascular biology and lung inflammationEndothelial MERTK receptor tyrosine kinasedifferent research area
MERTK in endothelial cells maintains barrier function and restrains neutrophil transendothelial migration, so deleting it specifically in endothelium should aggravate inflammatory lung injury.
Knocking MERTK down in primary human pulmonary microvascular endothelial cells increased neutrophil transmigration and dextran leak and disrupted adherens junctions and basal Rac1 activity, and global Mertk-null mice recruited more neutrophils and leaked more Evans blue during Pseudomonas aeruginosa pneumonia. But inducible endothelium-specific Mertk-null mice showed no difference from controls in either neutrophil migration into inflamed lungs or vascular permeability.
Why it matched: mechanism: Vascular & angiogenesis · failed the same way: Bypassed by compensatory signalling

Links in published research

Where this experiment's genes are known to matter outside its own research area, and the papers behind those links. Sources: Open Targets Platform and Europe PMC.