Transgenerational effects of neonatal hypoxia‐ischemia in progeny

Abstract

Neonatal hypoxia-ischemia (HI) affects 60% of low birth weight infants and up to 40% of preterm births. Cell death and brain injury after HI have been shown to cause long-lasting behavioral deficits. By using a battery of behavioral tests on second generation 3-week-old rodents, we found that neonatal HI is associated with behavioral outcomes in the progeny of HI-affected parents. Our results suggest an epigenetic transfer mechanism of some of the neurological symptoms associated with neonatal HI. Elucidating the transfer of brain injury to the next generation after HI calls attention to the risks associated with HI injury and the need for proper treatment to reverse these effects. Assessing the devastating extent of HI's reach serves as a cautionary tale to the risks associated with neonatal HI, and provides an incentive to create improved therapeutic measures to treat HI.

The effect of maternal pravastatin therapy on adverse sensorimotor outcomes of the offspring in a murine model of preeclampsia

“…1 and 2). Similarly, in a rat model of perinatal ischemia, the offspring of affected pups displayed transgenerational deficits in a second generation of untreated pups with similar locomotor outcomes and gender biases to those described here (Infante et al, 2013). Moreover, cerebral palsy, autism and neurodevelopmental delay are all more common in males than females (Peacock et al, 2012; Suren et al, 2012).…”

“…Mice underwent 5 trials on each day with 2 min rest periods. The average number of falls and average latencies for each offspring were used for analysis (Ferrari et al, 2010;Infante et al, 2013;Lalonde and Strazielle, 2011).…”

Epigenetics: Stress and disease

“…The demonstrated tissue specificity, sex selective responses and mechanistic epigenetic differences described in these two papers, an animal model of prenatal stress and human samples from diagnosed autistic patients is representative of the complex role of epigenetics in phenotype regulation (Grayson and Guidotti, 2016) and in the case of the animal model is consistent with other reports of transgenerational non‐genetic changes; of which some have been shown to also be sex specific (Blaze et al, 2015; Infante et al, 2013).…”

“…While representing a small sample of the epigenetic literature, these two papers reflect the complex linkage between environmental influences in development process to linkages to brain specific areas and sex specific changes already shown to have transgenerational effects (Infante et al, 2013; Prokopuk et al, 2015). Although a distinctions between developmental epigenetic processes and transgenerational epigenetic can be made on the basis of failure in the resetting of chromatin states in reproduction, it is likely to be an integrated process with sporadic evolutionary consequences (see also Blaze and Roth, 2015).…”

Maternal Pravastatin Prevents Altered Fetal Brain Development in a Preeclamptic CD-1 Mouse Model

“…Similarly, in models of neonatal hypoxia-ischemia, male rats show increased tissue damage and behavioral effects. Infante, et al showed that adverse locomotor outcomes were seen in offspring of affected pups, and gender bias was noted, suggesting an epigenetic mechanism as well [67]. The presence of a fragile Y chromosome which is susceptible to DNA modifications such as methylation may explain this [66], [68].…”