The pregnant spontaneously hypertensive rat as a model of asymmetric intrauterine growth retardation and neurodevelopmental delay

Introduction. Hypertension in pregnancy and vascular placental insufficiency are considered common pathogenic factors in human intrauterine growth retardation (IUGR). IUGR neonates experience higher mortality, and the surviving infants have a higher incidence of neurological and intellectual impairment. Methods. To mimic this condition, we used pregnant spontaneously hypertensive rats (SHR) and performed biometric measurements on Embryonic Day 20, postnatal developmental reflexes, and locomotor activity evaluations. Results. SHR fetuses had significant decreased body weight compared to the Wistar-Kyoto control fetuses (1.51 0.02 g vs. 2.05 0.01 g, respectively; p < 0.0001), and were relatively microcephalic (2.86 +/- 0.04 cm vs. 3.3 +/- 0.03 cm, respectively; p < 0.0001). Their cephalization index (head circumference/body weight) was increased (1.88 +/- 0.03 vs. 1.62 +/- 0.02, respectively; p < 0.0001), indicating a "brain-sparing'' process. The disproportional ratio indicated that the IUGR type in this model is asymmetric. The SHR pups exhibited a significant (p < 0.04) neurodevelopmental delay in the acquisition of neonatal reflexes (righting, negative geotaxis, placing), but they spontaneously caught up with the control pups after approximately 10 days. On Day 30, the SHR pups exhibited significantly increased walking speed and distance and spent less time in quadrant than the controls (p < 0.002). Conclusion. We speculate that the model of pregnant SHR closely simulate human IUGR caused by hypertension in pregnancy and should enable investigation of mechanisms of hypertension-mediated placenta- vascular injury as well as provide a system for preclinical evaluations of future preventive neuroprotective treatments.