The Effect of Two Types of Statins (Rosuvastatin and Atorvastatin) on the Fertility of Male and Female Mice

Abstract

Background: Studies showed controversial results regarding the effect of statins on fertility parameters. Several studies present evidence that statins have deleterious effects, others failed to prove these effects. Aim: To investigate the effects of rosuvastatin and atorvastatin on selected fertility parameters in male and female mice, and to find out their effects on first and second generations of offspring. Methods: For the first generation studies, mice [30 males and 60 females] were allocated into four groups (6-8 females and 3-4 males, matched for age, in each of the four groups). Rosuvastatin (3.5 mg/kg) or atorvastatin (10.6 mg/kg) was administered once daily for 21 days in a volume of 0.1 ml for each 20 g body weight. Number of live and dead pups, pregnancy success, pups weight, duration of pregnancy, male to female ratio, congenital anomalies, male serum testosterone levels, testes weight and dimensions, and testes histopathology were followed. For the second generation studies, male and female offspring mice were mated and followed for fertility, pregnancy success, and sexual maturity. Results: (i) First generation study: Although the changes in the measured fertility parameters induced by rosuvastatin were not statistically significant, there were trends toward lower number of pups in male and both (male and female) treated groups, lower pups weight in all treated groups, and lower serum testosterone and testes weight and dimensions in male-treated group when compared to control. Atorvastatin showed a statistically significant reduction in serum testosterone levels (-39.6%), lower testes weight (-13.3%), and mild to moderate histopathological changes in testes of male-treated group in comparison to untreated control group. There was lower number of pups (-6.8%) in male-treated. Pups weight in all treated groups and testes dimensions in male treated group showed trends toward lower values when compared to control. The male to female (M/F) ratio in the female-treated group was higher in both rosuvastatin experiment (1.17 versus 0.67 for control) and atorvastatin experiment (1.10 versus 0.72 for control). (ii) Second Generation Study: The only significant finding is longer time to delivery in mice born to treated mothers and fathers. The duration increased by 9.8% and 17% in rosuvastatin and atorvastatin experiments respectively in comparison to untreated control. Conclusion: Atorvastatin seems to have more harmful effects on fertility than rosuvastatin particularly with respect to their effect on male serum testosterone level and testes weight. The more male to female ratios after treating females with either statin is interesting and worth further investigation.