POHaD - Paternal Origins of Health and Disease: Paternal obesity and early embryonic development.

摘要

Several studies showed that female obesity has a negative impact on pregnancy, embryonic development, live birth rates and offspring's health. However, only a limited number of studies have investigated the impact of paternal lifestyle or obesity on these fertility and birth-related outcomes. In human, a link between Body Mass Index (BMI) of future fathers and the number of successful live births has been shown. Studies in animals have demonstrated that diet-induced obese males have impaired preimplantation embryo physiology and delayed embryonic development. Hence, we hypothesize that paternal periconception lifestyle and obesity can impair sperm quality and embryonic development in humans. As such, the aim of this study is to investigate the impact of paternal anthropo-metric characteristics on early embryonic development. We setup a longitudinal study in Belgian couples attending the Leuven University Fertility Center (LUFC). In this "Epigenetic Legacy of Paternal Obesity" (ELPO) study we will combine three consecutive stages of human development, including the male gametes, embryos and offspring. Our aim is to include at least 120 couples between 18-45 years old. We exclude patients with a history of cancer, radiation or chemotherapy, patients with pre-implantation genetic diagnosis, patients with subnormal sperm parameters or ICSI treatment, and use of frozen/ thawed sperm samples or donor gametes. Anthropometric data, including BMI, lean and fat %, and waist circumference are measured at the time of recruitment. Socio-demographic characteristics and information regarding lifestyle and dietary/ nutritional intake are collected through standardized questionnaires. Embryo growth is assessed through a computer assisted scoring system. In brief, number of blastomeres, symmetry and degree of fragmentation are recorded on day 1, day 2 and day 3, after insemination. From our preliminary data, we expect to have 60% overweight/obese men and 40% normal weight men in our study sample. Taking into account age, lean and fat mass are within the expected ranges; respectively 80% and 20%. It is our aim to explore potential associations between these anthropometric characteristics and early embryonic development, using mixed models accounting for clustering and control for potential confounding. In conclusion, this epidemiological study will improve our understanding of inheritance of paternal lifestyle factors. We believe that the current concept of the DOHaD needs an extension. Besides known maternal contributions to offspring's health, it is important to include preconceptional paternal exposures as well. Therefore, we suggest adding a POHaD (Paternal Origins of Health and Disease) theory in this Society of DOHaD.