Transgenerational effects following chronic circadian disturbance given to mother rats in F1 generation rats

Abstract

It has not been documented whether circadian disturbance of mother may influence fetal neurodevelopment. Therefore, this study aims to find the root cause of congenital neuronal defects, which is explosively increasing today, in one of the environmental factors; circadian disturbance. Female rats were randomly divided into 3 groups; L/D group with 12/12 hr light and dark cycle, LL group with 24 hr constant light, DD group with 24 hr constant dark. All subjected females were assigned to each light condition one week prior to pregnancy. Then, they were mated with males, and F1 offsprings were obtained at three weeks after the mating. The future generations were exposed exactly same light conditions. The animals in each group were randomly divided into control and melatonin‐treated subgroups. All animals were engaged in physiological, histological, and neurobehavioral analyses. LL and DD groups showed several abnormal features and decreased cecum/colon length (p<.05). Also, LL and DD groups showed lower activation of intracranial δ‐wave than L/D group showed. However, in LL and DD groups treated with melatonin improved intestinal integrity and activated intracranial δ‐wave. Axonal sprouting was evaluated by Golgi‐cox staining for identifying the abnormal neurodevelopment in all groups. The LL and DD groups showed reduction of axonal sprouting than L/D group. However, axonal branching in neuron increased in LL and DD groups treated with melatonin. In addition, neurobehavioral tests including open field test, novel objective recognition test, social interaction test, spontaneous alternation Y‐maze test, and elevated plus maze test were performed. LL and DD groups showed abnormal neurobehaviors (p<.05), whereas, melatonin treatment resulted in the normalized neurobehaviors (p<.05). In conclusion, F1 generation born from mothers exposed to chronic circadian disturbance showed abnormal neurodevelopment and neurobehaviors. Melatonin was considered as a therapeutic agent for congenital neuronal deficit.Support or Funding InformationFundings: National Research Foundation (NRF‐2017R1A2A2A01067169, NRF‐2019R1A6A3A01091422), Korea