ArticleAmerican journal of obstetrics and gynecology2025
Peripartum dapagliflozin improves late-life maternal cardiovascular outcomes in a murine model of superimposed preeclampsia.
Article in American journal of obstetrics and gynecology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed.
- Targeting metabolism to protect fertility and healthy pregnancy with SGLT2 inhibitors and GLP-1RAs.Current opinion in physiology · 2026Article
- Optimisation of maternal cardiometabolic outcomes after hypertensive disorders of pregnancy.Women's health (London, England)Review
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7 authors.
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Abstract
backgroundHypertensive disorders of pregnancy are important risk factors for later-life cardiovascular diseases. SGLT2 (sodium-glucose cotransporter-2) inhibition improves outcomes in heart failure, a later-life risk that disproportionately affects those with preeclampsia superimposed on chronic hypertension. SGLT2 inhibition during pregnancy and the postpartum period has not been effectively modeled or tested in superimposed preeclampsia as a potential cardiovascular risk-reducing intervention.
objectiveThis study aimed to (1) confirm the phenotype of superimposed preeclampsia in the BPH/2J mouse model, (2) test the short- and long-term obstetrical and cardiovascular effects of administering an SGLT2 inhibitor (dapagliflozin) in pregnancy and the immediate postpartum period in this model, and (3) identify molecular effects of SGLT2 inhibition in cardiovascular tissues during and after a treated pregnancy. STUDY
designWe established the BPH/2J model of superimposed preeclampsia and then randomly assigned pregnant BPH/2J mice with implanted telemetry devices to dapagliflozin-enriched chow or control chow starting early in gestation through 21 days after delivery. Maternal cardiovascular and obstetrical outcomes including circulating plasma protein markers, urine studies, obstetrical ultrasounds, and tissue histopathology were compared between the groups. Hearts and aortae were analyzed using serial echocardiography and spatial transcriptomics in late gestation or at 6 months postpartum.
resultsBPH/2J mice had baseline chronic hypertension that worsened in pregnancy with the development of proteinuria and elevated plasma sFlt-1 levels, consistent with superimposed preeclampsia. Mid-gestation systolic blood pressures were higher in the untreated group than the dapagliflozin-treated group (+2.87 mm Hg; P<.001). There were no differences in the number of pups or estimated fetal pup weights between the groups, whereas amniotic fluid volume, placental size, and markers of placental perfusion were improved in the dapagliflozin-treated group. The untreated group had higher aortic peak velocities in late pregnancy compared with the dapagliflozin-treated group (748.1 vs 561.9 mm/s; P=.004×10
conclusionIn a murine model of superimposed preeclampsia, dapagliflozin treatment during pregnancy and the puerperium improved physiological cardiovascular parameters during gestation and cardiac function later in life. This may be related to observed molecular effects of SGLT2 inhibition treatment, particularly its antifibrotic and metabolic actions associated with reduced markers of fibrotic pathologic remodeling in treated BPH/2Js during and after pregnancy.
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