School of BioSciences - Theses
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ItemMale obesity negatively affects fecundity; reducing seminal plasma quality, embryo physiology and pregnancy health( 2015)Australia is echoing trends seen across the globe with steadily increasing rates of obesity. Worldwide, the rate of obesity has nearly doubled in the past three decades, and in particular, obesity amongst men of reproductive age has tripled. While an association between excessive weight and subfertility is now largely recognised, the consequences of male obesity on reproductive function are poorly understood. The aim of the work carried out in this thesis was to investigate the effects of male obesity on preimplantation embryo development and subsequent fetal health, and identify changes in the spermatozoa and seminal plasma of obese men that might result in compromised pregnancies. The glut of data regarding the effect of male obesity on fertility, implantation and pregnancy health originates from fertility clinics, with study cohorts biased towards a subfertile population and influenced by numerous lifestyle factors. Comparatively, animal models are free of confounding variables. Male C57Bl/6 mice were fed a high fat ‘Western fast food’ style diet to induce obesity, and used for sample generation. Obese mice gained significantly more weight than their normal counterparts and had significantly increased body fat. Appropriately timed development is a key indicator of embryo quality. Embryos were examined under time-lapse microscopy to assess timing of cleavage events. Embryos derived from obese males were slower than normal from as early as pronuclear fusion. These embryos also had aberrant preimplantation metabolism and mitochondrial membrane potential, as well as disproportionate allocation of cells to the inner cell mass and trophectoderm. When these embryos were transferred to recipient female mice, embryos derived from obese fathers resulted in a successful pregnancy less often than their normal counterparts. Further examination revealed this to be the result of poor embryo implantation. Modelling attachment and the initial stages of implantation in vitro showed embryos derived from obese fathers attached to the extracellular matrix at the same rate as normal, but had decreased outgrowth over the culture period. When embryos derived from obese fathers did result in a successful pregnancy, placentas were significantly smaller than normal and fetal growth was restricted. While male and female fetuses appeared equally affected morphologically, molecular changes as a result of paternal obesity were identified as sex-specific. Female placentas derived from obese fathers had significantly increased global DNA methylation, and male placentas had altered RNA levels of a number of key metabolic and apoptotic genes. These changes in embryo, fetal and placental development do not appear to be the result of gross morphological changes to the spermatozoa of obese males. Total sperm count, motility and acrosomal reaction were all unaffected by obesity. However, RNA levels of cytochrome c oxidase subunit IV isoform 1 were significantly higher in the spermatozoa of obese males compared to normal. Furthermore, the protein and carbohydrate milieu of the seminal plasma was significantly affected by obesity. The findings within this thesis demonstrate the significant effect of male obesity on reproductive fitness, affecting preimplantation embryo development and subsequent pregnancy health, as well as seminal plasma composition. Furthermore, this work highlights the importance of paternal health prior to conception, a factor often overlooked in the making of a healthy baby.