Abstract
Worldwide, 48% of adult males are overweight or obese. An association between infertility and excessive body weight is now accepted, although focus remains primarily on females. It has been shown that parental obesity results in compromised embryo development, disproportionate changes in embryo metabolism and reduced blastocyst cell number. The aim of this study was to determine whether paternal obesity has negative effects on the resultant embryo. Specifically, using in vitro fertilisation (IVF), we wanted to isolate the functional effects of obesity on sperm by examining the subsequent embryo both pre- and post-implantation. Epididymal sperm was collected from age matched normal and obese C57BL/6 mice and cryopreserved for subsequent IVF with oocytes collected from Swiss females (normal diet/weight). Obesity was induced in male mice by feeding a high fat diet of 22% fat for 10 weeks. Resultant embryos were cultured individually and development monitored using time-lapse microscopy. Paternal obesity resulted in a significant delay in preimplantation embryo development as early as syngamy (P<0.05). Metabolic parameters were measured across key developmental stages, demonstrating significant reduction in mitochondrial membrane potential (P<0.01). Blastocysts were stained to determine trophectoderm (TE) and inner cell mass (ICM) cell numbers, revealing significant differences in the ratio of cell allocation to TE and ICM lineages (P<0.01). Functional studies examining blastocyst attachment, growth and implantation demonstrated that blastocysts derived from sperm of obese males displayed significantly reduced outgrowth on fibronectin in vitro (P<0.05) and retarded fetal development in vivo following embryo transfer (P<0.05). Taken together, these data clearly demonstrate that paternal obesity has significant negative effects on the embryo at a variety of key early developmental stages, resulting in delayed development, reduced placental size and smaller offspring.
Highlights
Excessive body weight continues to be a significant problem plaguing modern society, and contrary to popular opinion, is not restricted to Western culture
Most research has focused on maternal obesity, there is growing data to indicate that paternal obesity is a cause for concern
Obesity Effects on Embryo Developmental Kinetics Embryos generated from the sperm of obese males showed significant delays in preimplantation development from as early as syngamy
Summary
Excessive body weight continues to be a significant problem plaguing modern society, and contrary to popular opinion, is not restricted to Western culture. There are more overweight people in the world than there are undernourished, estimated at 1.5 billion and 1 billion respectively [1]. The prevalence of overweight and obesity among the adult male population is exceedingly high, with countries such as USA, Nauru, Australia, Argentina, Greece and Samoa seeing rates increasing above 75% and 30% respectively [2]. Obesity is associated with numerous health problems, including cardiovascular disease, type 2 diabetes, hypertension, liver disease, psychosocial problems, cancer and infertility. The rate of obesity amongst men of reproductive age has tripled over the last three decades [3]. Most research has focused on maternal obesity, there is growing data to indicate that paternal obesity is a cause for concern
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