061. PATERNAL FACTORS INFLUENCING GESTATIONAL OUTCOME IN OFFSPRING

Abstract

Fetal programming can often be attributed to sub-optimal, but potentially modifiable, maternal factors such as smoking and poor nutrition. Much of the literature in this field points to factors that cause intrauterine growth restriction (IUGR) and the long term consequences for offspring health. It is not greatly appreciated, however, that other complications that may occur with, or independently of, IUGR predispose offspring, and their mothers, to poor health. These include preeclampsia and gestational diabetes. Elevated maternal BMI increases the risk for most pregnancy complications. Our new data show that paternal obesity (BMI>30) and waist circumference >102cm are associated with IUGR. We have also identified polymorphisms in a number of genes that regulate how the placenta differentiates and invades the maternal decidua, and how the mother adapts to pregnancy, that are associated with adverse pregnancy outcomes. Excitingly, many of these are polymorphisms in the paternal genome. One might reasonably expect that these would be found in imprinted genes expressed only from the paternal allele. However, we have also found several non-imprinted genes in which paternal genotype has a significant influence on pregnancy outcome both on maternal and infant disease states, but also on fetal and placental growth parameters. Furthermore, these genes interact with the maternal environment including diet and smoking to profoundly affect maternal and infant health. Consequently we now propose a complicated model of the control of optimal placental and fetal growth and pregnancy outcome that includes important genetic contributions from both parents to placental genotype that regulate conceptus growth and function. Importantly, paternal genotype can influence placental gene expression and the myriad of placental hormones and growth factors secreted into the maternal circulation that modulate maternal adaptation to pregnancy and, in susceptible women, these interact with maternal genotype, BMI and lifestyle to cause poor maternal and infant health.