PS-B05-9: ADVANCED MATERNAL AGED MOUSE MODEL SHOWED FETAL GROWTH RESTRICTION AND WOULD BE A MODEL FOR DOHAD

Abstract

Backgrounds: The number of advance-aged pregnancies, defined as those over 35 years of age, has been increasing in developed countries due to tendency to marry later with women's social advancement and assisted reproductive technology. Furthermore, in Japan, the incidence of hypertensive disorders of pregnancy over 40 years of age is as high as approximately 8%, which have a high rate of premature births and low birth weight, and fewer nephrons. Recently, based on the developmental origins of health and disease (DOHaD) hypothesis, it has been recognized that the risk of developing hypertension, proteinuria and renal failure in the future is increased in aged pregnancies. However, the detailed mechanism is uncertain. Methods: Female ICR mice of 6 to 10 months (Advanced maternal age, AMA group) and of 10 to 12 weeks (Control; CON group) were mated with males of 10 to 16 weeks. Blood pressure during pregnancy on day 7 and 14 was measured in both groups (n = 4, n = 4). The pups born in both groups (AMA, n = 4–13; CON, n = 10–16) were weighed at postnatal day 0, a week, 4 weeks, and 8 weeks of age. Blood pressure (n = 7, n = 3) at 8 weeks of age was measured using the tail-cuff technique. The results were compared using the Mann-Whitney U test. Results: There was no difference in blood pressure during pregnancy on day 7 and day 14 in both groups. In the AMA mouse model, the weights of postnatal day 0 pups were significantly lower (AMA vs. CON, 1.66 ± 0.22 g vs. 1.9 ± 0.22 g, P = 0.006). However, no difference was found between the two groups at a week and 4 weeks. Conversely, the body weights of the AMA model were significantly higher at 8 weeks of age (AMA vs. CON, 47.7 ± 3.43 g vs. 45.4 ± 2.8 g, P = 0.041) and the systolic blood pressure in the AMA group tended to be higher. Discussion/Conclusion: In the present study, the AMA mouse model induced fetal growth restriction and subsequently showed catch-up growth. Furthermore, their pups’ weights were significantly higher and elevated blood pressure was observed at adult age. While previous animal models of DOHaD have been mainly based on studies of dietary restriction, chemical exposure, and preeclampsia, this model showed similar symptoms to DOHaD models.