Postnatal high-fat diet consumption by male rat offspring of obese mothers accentuates negative outcomes of reproductive function in young adults†.

Maternal obesity (MO) predisposes male offspring to impaired fertility and premature aging of reproductive function. We hypothesized that postnatal high-fat diet (HF) from early childhood to adulthood (second hit) exacerbates MO programmed outcomes in male offspring reproductive capacity. Female Wistar rats ate chow (5%-fat (C)) or HF diet (25%-fat (MO)) from weaning through pregnancy and lactation. Male offspring were weaned on chow (C/C and MO/C) or HF diet (C/HF and MO/HF) and euthanized at postnatal-day 110. Scrotal temperature and epididymal fat were higher in C/HF and MO/HF. Testicles: malondialdehyde (MDA) concentrations were increased in MO/HF, reactive oxygen species (ROS) rose in MO/C and MO/HF, superoxide dismutase (SOD) activity increased in C/HF and MO/HF, and glutathione peroxidase (GPx) activity was higher in C/HF, MO/C, and MO/HF. Testicular mRNA expression of Nrf2, SOD-1, GPx-4, and Bax/Bcl2 ratio was lower in MO/HF. Sperm: MDA concentrations increased in MO/HF, ROS concentrations were elevated in MO/C and exacerbated in C/HF and MO/HF, SOD activity decreased in MO/HF. Sperm motility decreased, while sperm abnormalities increased in C/HF, MO/C, and MO/HF. DNA fragmentation: yellow-stained sperms (low-fragmentation) were increased in MO/C and exacerbated in C/HF and MO/HF; C/HF, MO/C, and MO/HF showed more orange-stained sperms (medium-fragmentation), but MO/HF had the highest increase. MO/HF exhibited an increase in red-stained sperms (high-fragmentation). MO/HF had a decreased fertility rate. MO combined with postnatal environmental factors, has a negative impact on offspring health and leads to greater reproductive alterations in comparison with unhealthy postnatal dietary habits or the programming caused by MO.