Intrauterine growth restriction and neonatal hypoxic ischemic brain injury causes sex‐specific long‐term neurobehavioral abnormalities in rats

Abstract

There is a lack of knowledge of factors preventing an adequate response to moderate hypothermia after hypoxic ischemic (HI) brain injury. We hypothesized that growth restriction from reduced intrauterine perfusion would predispose neonatal rats to have a worse outcome with HI brain injury. IUGR was induced by placental insufficiency in dams at 14 days of gestation. HI was induced at postnatal day (P) 10 by permanent right carotid artery ligation followed by 90 min of hypoxia (8% oxygen). Tests for early brain injury and neurobehavioral outcomes were subsequently done. All statistical analysis was done using Two‐way ANOVA; post hoc Holm‐Sidak test. HI in control and IUGR groups decreased the success rate of the contralateral vibrissa‐elicited forelimb test, increased response latency in movement initiation test and increased the time to finish elevated beam walk test at P40 and P60. IUGR augmented HI‐induced abnormality in vibrissa‐elicited forelimb test at P40 but showed higher success rate when compared to HI only group at P60. IUGR’s negative effect on HI‐induced changes on the elevated beam walk test was sex‐specific and exaggerated in P60 males. Increased TUNEL positive cells in the cortex were noted at 72 h after in HI in control but not in IUGR groups. In conclusion, the consequences of IUGR on subsequent neonatal HI varied based on age, sex and outcomes examined, and overall, male sex and IUGR had worse effects on the long‐term neurobehavioral outcomes following HI.

Cytoplasmic m1A reader YTHDF3 inhibits trophoblast invasion by downregulation of m1A-methylated IGF1R

“…Downregulation of placental IGF1R might be an important factor in pregnancies complicated by intrauterine growth restriction (IUGR) 29 . Recent report has also shown a significant downregulation of IGF1R protein levels in IUGR pregnancies compared to normal pregnancies 30,31 . Interestingly, IGF1R protein downregulation in IUGR placentas was accompanied by impaired activation of intracellular signaling molecules of the IGF1R 32,33 .…”

Intrauterine Growth Restriction Followed by Oxygen Support Uniquely Interferes with Genetic Regulators of Myelination

“…A number of clinical studies have identified male sex as an independent risk factor for poor neurodevelopmental outcomes in prematurity (Hintz et al, 2006;Sunny et al, 2020) and hypoxic-ischemic (HI) injury (Mirza et al, 2015;Narang et al, 2019). A sex bias has also been identified in children with CP, with males being more affected than females (Johnston and Hagberg, 2007).…”