Toxic effects of 1-(N-methyl-N-nitrosamino)-1-(3-pyridinyl)-4-butanal on the reproduction of female mice

Abstract

Cigarette smoke can affect female reproductive health by causing follicle destruction and oocyte dysfunction. Third-hand smoke has received increasing attention as a public health issue. However, the effects of third-hand smoke on the female reproductive system, particularly the ovaries, remain unclear. 1-(N-methyl-N-nitrosamino)-1-(3-pyridinyl)-4-butanal (NNA) can be used as a biomarker of third-hand smoke. We studied the in vivo toxic effects of NNA on mice ovaries and offspring development. Three-week-old premature female mice were exposed to NNA at two different concentrations (0.075 μg/kg and 0.15 μg/kg body weight) and tap water (blank control) and diluted dimethylsulfoxide (solvent control) for 30 days. We found that oral administration of NNA (0.075 μg/kg and 0.15 μg/kg) significantly reduced ovary weight (the 0.15 μg/kg group was reduced to 18.69% ± 0.89%) and ovarian follicle number (reduced by about 30%) (p < 0.05). Consumption of 0.15 μg/kg NNA reduced the survival rate of superovulated oocytes from 91.36% to 60.55% (p < 0.05). In addition, treated female mice in each group were mated with normal male mice to observe the effects of NNA on the F1 offspring, and during mating and lactation, all groups were given tap water. Two different concentrations of NNA exposure also significantly reduced body weight and impaired ear opening, tooth eruption and eye opening in F1 offspring, especially those exposed to 0.15 μg/kg NNA (p < 0.05). Our study suggested that NNA exposure had toxic effects on the reproductive health of female mice and their offspring. The results obtained may help evaluate the risks of third-hand smoke to women's reproductive health and to the health of their offspring.