103. THE EFFECT OF PATERNAL OBESITY IN MICE ON REPRODUCTIVE AND METABOLIC FITNESS OF F1 MALE OFFSPRING
journal contribution
posted on 2024-07-25, 02:49authored byM Mitchell, T Fullston, NO Palmer, HW Bakos, Julie OwensJulie Owens, M Lane
We know relatively little of the consequences of male obesity for reproductive success compared to female obesity. Conflicting evidence exists in both humans and rodents regarding whether paternal obesity alters sperm motility and concentration. However, we have described impaired embryo and fetal development, and implantation, in rodents as a consequence of paternal obesity. This study investigated whether founder male obesity influenced the reproductive and metabolic fitness of males of the subsequent F1 generation. C57BL/6 founder male mice were fed a standard chow (CD) or a high-fat diet (HF) for 8wks. This increases adiposity in the absence of changes in fasting glucose levels. Males were mated to female C57BL/6 mice, and subsequent m ale F1 offspring from HF (HF-F1) or CD (CD-F1) founders were weighed weekly and maintained on standard chow. At 8 weeks and 14 weeks glucose tolerance tests were performed and following euthanasia, tissues and sperm collected. Sperm reactive oxygen species (ROS) and DNA damage levels were determined, and various organs weighed. HF-F1 male pups were significantly heavier relative to CD-F1 males (P < 0.05) although adult bodyweight did not differ significantly. Despite this, liver, pancreas, testes and epididymis weight was significantly elevated for HF-F1 males at 17wks of age (P < 0.05). At both 8wks and 14wks of age HF-F1 males were hypoglycaemic and had impaired glucose metabolism. Sperm analysis of HF-F1 males indicated a significant increase in ROS levels (P < 0.05), DNA damage (P < 0.05) and a decrease in fertilization rates in vitro (P < 0.05). This data indicates significant physiological changes and perturbed sperm parameters in F1 males as a consequence of founder male obesity. It supports further interrogation of male and female F1 offspring, and warrants examination of potential effects for a subsequent F2 population.