Neonatal Goitrogen Treatment Increases Adult Testis Size and Sperm Production in the Mouse

ABSTRACT Male rats made hypothyroid during neonatal life show unprecedented increases in adult testis size and daily sperm production (DSP). To determine if this effect was unique to the rat or could also be demonstrated in other species, we examined the effects of neonatal treatment with the reversible goitrogen 6‐propyl‐2‐thiouracil (PTU) on adult testis size and function in the mouse. Male Swiss‐Webster mice were untreated (control) or given PTU by adding 0.1% (w/v) to their mother's water from birth to day 25 postpartum. All pups were then weaned and given no further treatment. Sertoli cell proliferation was examined using tritiated thymidine autoradiography in some control and treated mice at 0, 5, 10, 15, 20, and 25 days, while the remainder were killed at 90 days to determine a variety of reproductive parameters. Neonatal PTU treatment decreased growth; body weight of treated mice at 4 weeks of age was 57% less than controls. Treated mice grew rapidly following cessation of PTU treatment, although their weights never equalled controls, remaining 17% smaller at 90 days of age. At 90 days of age, testis weight and DSP were increased by approximately 30% and 50%, respectively, in PTU‐treated mice compared to controls. Despite the increased testis weight and function, serum testosterone concentrations were not different in control and treated mice. Testicular and epididymal histology in treated mice was similar to controls, while epididymal sperm in treated mice were motile and morphologically normal. Sertoli cell proliferation was altered in treated mice. The normal decrease in proliferative rate seen during early postnatal life was slowed, and by day 10 postnatal, the labeling index of treated Sertoli cells was about fourfold greater than that of controls. Furthermore, Sertoli cells in treated mice proliferated until day 25, whereas proliferation ceased in controls by day 15. In summary, neonatal PTU treatment increases testis weight, DSP, and the efficiency of sperm production (DSP/g testis) in the mouse, indicating that the PTU effect on testis development clearly occurs in other species. Furthermore, increased Sertoli cell proliferation appears to be the critical event for the development of this phenomenon in mice, as it is in rats. The existence of unique mutations that affect testicular development make the mouse an advantageous model for determining the mechanism of this effect. This technique may also be useful for increasing testicular size, sperm production, and fertility in various mutant mouse strains and transgenic mice in which these parameters are reduced.