Yin Zhou1,2, Hong Zhu1, Hai-Yan Wu1, Lu-Yang Jin1, Bin Chen1, Hai-Yan Pang1, Zhen-Hua Ming1, Yi Cheng1, Cheng-Liang Zhou1, Meng-Xi Guo3, Yi-Ting Huang2, Dan-Qing Yu2, Jian-Zhong Sheng1,4, He-Feng Huang1,3. 1. Key Laboratory of Reproductive Genetics, Ministry of Education, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. 2. Center for Reproductive Medicine, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. 3. International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. 4. Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Abstract
OBJECTIVE: This study aimed to determine the effects of diet-induced paternal obesity on cognitive function in mice offspring. METHODS: Male mice (F0) were randomized to receive either a control diet (10 kcal% fat) or a high-fat diet (HFD; 60 kcal% fat) for 10 weeks before being mated with normal females to generate F1 offspring. Male F1 offspring were mated with normal females to generate F2 offspring. Behavioral tests were used to assess cognitive functions in F1 and F2 offspring. Reduced representation bisulfite sequencing was used to the explore mechanisms of epigenetic inheritance. RESULTS: HFD-induced paternal obesity resulted in cognitive impairments in F1 offspring, potentially due, at least in part, to increased methylation of the BDNF gene promoter, which was inherited from F0 spermatozoa. BDNF/tyrosine receptor kinase B signaling was associated with cognitive impairments in HFD-fed F1 offspring. However, there were no significant changes in F2 offspring. CONCLUSIONS: The findings provide evidence of intergenerational effects of paternal obesity on cognitive function in offspring occurring via epigenetic spermatozoan modifications.
OBJECTIVE: This study aimed to determine the effects of diet-induced paternal obesity on cognitive function in mice offspring. METHODS: Male mice (F0) were randomized to receive either a control diet (10 kcal% fat) or a high-fat diet (HFD; 60 kcal% fat) for 10 weeks before being mated with normal females to generate F1 offspring. Male F1 offspring were mated with normal females to generate F2 offspring. Behavioral tests were used to assess cognitive functions in F1 and F2 offspring. Reduced representation bisulfite sequencing was used to the explore mechanisms of epigenetic inheritance. RESULTS: HFD-induced paternal obesity resulted in cognitive impairments in F1 offspring, potentially due, at least in part, to increased methylation of the BDNF gene promoter, which was inherited from F0 spermatozoa. BDNF/tyrosine receptor kinase B signaling was associated with cognitive impairments in HFD-fed F1 offspring. However, there were no significant changes in F2 offspring. CONCLUSIONS: The findings provide evidence of intergenerational effects of paternal obesity on cognitive function in offspring occurring via epigenetic spermatozoan modifications.