FEASS[Twins]

Research from animal models has shown that the diets of males prior to conception cause phenotypic alteration of subsequent offspring, including modulation of metabolism, development, and cognitive function. These models also indicate that dietary perturbation causes epigenetic reprogramming of the male germline, indicating that diet-induced spermatozoa epigenetic modulation is likely a key mechanism underlying the inherited phenotypes caused by paternal nutrition. Epidemiological studies identify that a correlative link exists between paternal nutrition and offspring health, such as paternal famine exposure being associated with offspring diabetes and obesity, and paternal obesity being associated with increased risk of offspring obesity, mortality and autism spectrum disorder.

Nonetheless, the impact of paternal diet on the sperm epigenome and offspring health has undergone minimal investigation in humans and warrants further study. The purpose of this study is to elucidate the role of acute dietary intake in male populations, and its impact on spermatozoa quality, integrity, content and epigenetic programming. We will study this relationship utilising a co-twin randomised design in order to investigate monozygotic twin pairs that are discordant for nutritional exposure.

Studying this phenomenon in a population of twins gives us the unique advantage of studying the epigenetic modulation in individuals with highly overlapping genomes, along with studying subjects which have generally similar baseline physiological parameters and highly comparable pre and perinatal experiences.

For this study, we will provide twin male pair participants with discordant prescribed diets for a three-week increment, and we will collect health information and biological samples prior to and after delivery of the dietary intervention. The diets will consist of a “Processed diet” mimicking a traditional western dietary intake pattern and an “Unprocessed diet” based upon current dietary guidelines at quantities adequate for the participants energetic needs.

We have chosen to study these two dietary patterns to compare the physiological effects of consuming dietary patterns mimicking what men are supposed to eat versus what they are actually eating.  The processed diet is based on the typical dietary intake patterns of American men aged 19-30. Food and beverage products provided will fall into the category of processed foods and ultra-processed foods in accordance with the NOVA food processing classification system. The unprocessed diets will meet the Nordic and Australian dietary guidelines for food groups and micronutrients. Food and beverage products provided will fall into the category of unprocessed/minimally processed foods and processed culinary ingredients in accordance with the NOVA food processing classification system.

We have designed these diets to be macronutrient matched, wherein both the processed and unprocessed diets provide 49% of kcal from carbohydrates, 35% from fat, and 16% from protein, to control for macronutrient variability as a confounding factor, and focus on the quality and content of food products provided on the induced effects.

Biological specimens and survey information from participants will be collected before and after the nutrition intervention.  This includes assessment of anthropometric characteristics, survey information surrounding lifestyle, physical, and mental health, classical semen quality characteristics, serum metabolic markers, reproductive hormones, stress hormones and appetite hormones.  Biological samples collected include blood, semen and saliva. Comprehensive profiling of fertility parameters will be conducted on the participants, characterising their levels of reproductive hormones before and after dietary intervention, the metabolomic content of seminal plasma, and sperm assessment of volume, count, viability, motility, morphology, and DNA fragmentation.  Following conclusion of the intervention, the fraction of mature spermatozoa from the participants collected before and after the dietary intervention will be further analysed for epigenetic features.  Specifically, we will conduct smallRNA sequencing, reduced representation bisulfite sequencing and ATAC-sequencing in order to determine how the sperm epigenome is remodelled following the acute dietary interventions.