From Gamete to Grandparent: The Paternal Programming of Adult Health Event

Time:: 13:00 - 14:00
Date:: 4 May 2016
Venue:: Building 85, Room 2207

For more information regarding this event, please telephone Karen Hood-Cree on 02380 598148 or email klhc1r11@soton.ac.uk .

Event details

Adult-onset metabolic diseases such as obesity, type 2 diabetes and cardiovascular disease, are associated typically with adult lifestyle factors including diet, exercise and smoking. However, studies using human populations and a diverse range of animal species have shown that adult disease risk is closely associated with perturbed environmental conditions experiences during the earliest stages of life. While the association between poor maternal gestational diet and adverse offspring adult health has been studied in detail, our understanding of the impact of paternal diet on adult offspring health remains largely neglected.

Using the well characterised rodent low protein diet (LPD; 9 % protein) model, we have determined the impact of paternal nutrition on the health and development of his offspring. Here, we observe that offspring from LPD fed males have significantly increased weight at birth and adult body fat levels, impaired glucose tolerance and cardiovascular dysfunction (indicative of obesity, type 2 diabetes and heart disease) when compared to offspring from control, normal protein diet (NPD: 18% protein) diet fed male mice. During gestation, fetal growth and skeletal volume are increased, associated with altered expression of placental transporters of amino acids, glucose and calcium. However, skeletal bone density is impaired significantly. To determine underlying molecular mechanisms linking paternal LPD to altered post-fertilisation development, we analysed sperm and testicular tissue from NPD and LPD fed males. We observed that sperm from LPD fed males were hypomethylated at genes for calcium signalling and bone development, while the expression of key epigenetic regulators (Dnmt’s and 1-Carbon metabolite intermediates) were reduced significantly in LPD fed male testes. Interestingly, at the time of embryo implantation (3.5 days after fertilisation), we observed significant changes in uterine cytokines and expression of prostaglandin synthesis and inflammatory mediator genes. These novel data suggest that paternal diet, at the time of conception, affects maternal uterine environment, fetal growth, skeletal formation and placental development. 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.

Speaker information

Dr Adam Watkins,Aston University, School of Life Sciences,