Mitochondrial-Targeted Antioxidant Attenuates Preeclampsia-Like Phenotypes Induced by Syncytiotrophoblast-Specific Gaq Signaling

This experiment explored the placental transcriptomic effects of syncytiotrophoblast-specific Gaq signaling at gestational day 14.5 in mice and assessed whether these responses were altered upon administration of a mitochondrial-targeted antioxidant. Overall design: Activation of the Gaq cascade in syncytiotrophoblast cells was achieved by crossing dams harboring a Cre-dependent Gaq-coupled DREADD (hM3Dq) with Gcm1-Cre+/- sires to elicit syncytiotrophoblast-restricted hM3Dq expression in ~50% of placentas within a dam. The synthetic DREADD ligand clozapine N-oxide (CNO; 2 mg/kg/d, ip) or saline (2 mL/kg/d, ip) was administered mid-gestation (gestational days 12.5-14.5) before the profiling of placenta gene expression at gestational day 14.5. In a separate cohort of double transgenic (hM3Dq+, Gcm1-Cre+) pregnancies, the mitochondrial-targeted antioxidant, Mitoquinone (MitoQ; 5 mg/kg/d, ip), was co-administered with CNO.