147. PATERNAL OBESITY IMPAIRS SPERM FUNCTION AND SUBSEQUENT EMBRYO AND PREGNANCY OUTCOMES

Abstract

Despite the increased prevalence of obesity in males of reproductive age, the effects of male obesity on conception and pregnancy have been largely ignored. Hence, the aim of this study was to elucidate the effects of paternal Diet Induced Obesity (DIO) on sperm function, embryo development and pregnancy. Six week old C57BL/6 male mice (n=36) were allocated to either standard chow or a high fat diet (HFD). After eight weeks, mice were either sacrificed and spermatozoa assessed, for motility, reactive oxygen species (ROS) and DNA damage or mated and zygotes collected and cultured to the blastocyst stage. Blastocyst development, cell number and apoptosis were assessed, and fetal outcomes analyzed following embryo transfer. Differences between treatments were assessed using GLM. The percentage of motile spermatozoa was decreased (36% vs. 44%, p<0.05) in the HFD group compared to controls. Intracellular ROS were elevated (692units vs. 409units, p<0.01) in the HFD group compared to controls. Overall levels of sperm DNA damage were also increased (1.64% vs. 0.17%, p<0.05) in the HFD group. Blastocyst development was reduced when males were fed a HFD (64% vs. 84%, p<0.05). Similarly, blastocyst cell number (37.9±2.8 vs. 46.6±2.5, p<0.05), inner cell mass number (11.4±0.9 vs. 15.3±0.9, p<0.05) were reduced and apoptosis (12.8±1.9 vs. 6.6±0.6, p<0.05) increased in embryos sired by a male fed a HFD. Implantation (86.7% vs. 72.5%, p<0.05) and fetal development (38.7% vs. 22.5% p<0.05) were also significantly reduced when blastocysts came from a male fed a HFD. This is the first report providing comprehensive evidence that paternal DIO significantly impairs embryo quality and pregnancy rates. These effects may be related to the observed increase in oxidative stress and sperm DNA damage. These data provide compelling evidence that male obesity impacts on male fertility, embryos as well as pregnancy and therefore studies in human are warranted.