In Australia, 75% of adult males are overweight or obese, greatly exceeding the global average of 48%. Furthermore, the rate of obesity among men of reproductive age has more than tripled in the last three decades. Associations between infertility and excessive body weight are now accepted, though focus remains primarily on females. Previously we demonstrated that paternal obesity resulted in compromised preimplantation embryo development, altered metabolic function and reduced inner cell mass to trophectoderm ratio in the blastocyst. Here we hypothesise that paternal obesity negatively impacts sperm, resulting in compromised fetal development as a result of impaired implantation and placentation. This study used in vitro fertilisation (IVF) to isolate the effects of paternal obesity on sperm; and subsequent embryo implantation and fetal development.

Epididymal sperm was collected from control (normal diet/weight) and obese C57BL/6 mice and cryopreserved for subsequent IVF with oocytes collected from control Swiss females. Generated embryos were cultured individually for 4 days at which point either embryo outgrowth on fibronectin, or embryo transfer to day 3.5 pseudopregnant females was performed to assess attachment and implantation/fetal development respectively.

The extent of blastocyst outgrowth in vitro was significantly reduced (P<0.05) compared to control. However, paternal obesity did not affect blastocyst attachment to fibronectin (77% vs. 79% respectively, P=0.68). The rate of blastocyst implantation in vivo decreased with paternal obesity (P<0.01), together with fetal development rate (P<0.05). Furthermore, both fetal and placental weights were significantly less for conceptuses derived from the sperm of obese males (P<0.05), and fetuses were morphologically retarded (P<0.01). These findings indicate that paternal obesity not only negatively affects preimplantation embryo development, but further impacts on embryo implantation, resulting in aberrant placentation and subsequent changes in fetal growth and morphological development of the offspring.