Gender Specificity of the Effect of Neonatal Melatonin Administration on Lifespan and Age-Associated Pathology in 129/Sv Mice

Abstract

Melatonin is subcutaneously administered in a single dose of 1.2 μg to 129/Sv mice at days 3, 5, and 7 after birth, and the mice are observed until natural death. In adult males, a decrease in the body weight and a reduction of the contribution of lung lesions detected during postmortal autopsy to mortality are detected. In adult females, an increase in the proportion of mice with impaired estrous cycle at the later stages of life and an acceleration of the mortality associated with uterine hemangioma are observed with the absence of any effect of melatonin on the body weight. Changes in the frequency of detection of other tumors are multidirectional: there is a decrease in the frequency in males and an increase in females. The age of death of the last 25% and 10% of males increases, while in females it decreases. An analysis of the complete survivorship curves using the Gompertz model does not reveal changes in the rate of aging and initial mortality sufficient to go beyond the limits determined by the artifact component of the Strehler–Mildvan correlation between these parameters. In general, the tendencies noted in males and females are multidirectional: favorable and unfavorable, respectively. Melatonin is contraindicated for pregnant and nursing women and children under 18 years old. The gender specificity of the effects of melatonin, apparently, should be considered when assessing the feasibility of its prescription to these categories.