Human and animal models have demonstrated the importance of maternal gestational diet for fetal growth, placental function and long-term offspring health. However, the impact of paternal diet on offspring development remains under-investigated. We have demonstrated that a paternal low protein diet (LPD 9% protein), programmes elevated offspring weight at birth, adult adiposity, glucose intolerance and cardiovascular dysfunction when compared to offspring from control normal protein diet (NPD 18% protein) fed male mice. As perturbed weight at birth is a critical indicator of cardio-metabolic disease risk in adult life, our current study investigated the impact of paternal LPD on post-fertilisation development and fetal growth. Male C57BL6/J mice were fed either NPD or isocaloric LPD for 7 weeks prior to mating. Analysis of NPD and LPD E3.5 blastocyst AMPK pathway by PCR array (Qiagen), revealed reduced LPD expression of receptor signalling, signalling cascades, protein synthesis, transcriptional regulation and metabolism genes (17 in total P<0.05). In late gestation (E17), fetal and placental weight were increased and decreased respectively in LPD offspring (P<0.05). In LPD placentas, reduced labyrinth and increased junctional zone proportions were observed (P<0.05), with increased transcript expression of calcium, (Atp2b1), amino acid (Slc38a2) and glucose (Slc2a1, Slc2a4) transporters when compared to NPD placentas (P<0.05). In LPD fetal liver tissue, reduced transcript expression of Adipor1, Akt2, Prkaca, Prargc1a and Trp53, (P<0.05) were observed, all reduced in LPD blastocysts. Micro-CT analysis of E17 fetal skeletal development revealed significantly increased low-density and decreased high-density bone in LPD offspring when compared with NPD offspring (P<0.05). These novel data suggest that paternal diet, at the time of conception, affects blastocyst metabolism, fetal growth, skeletal formation and placental development. Altered blastocyst metabolism and enhanced fetal growth may originate from adaptive mechanisms initiated to ensure short-term survival in the offspring, but which ultimately become maladaptive in adult life.
11 Jul 2016 - 11 Jul 2016