Neonatal polychlorinated biphenyl treatment increases adult testis size and sperm production in the rat

Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants which decrease serum thyroxine (T4) concentrations. We have previously demonstrated that neonatal hypothyroidism in the rat increases Sertoli cell numbers, adult testis weight, and daily sperm production (DSP). The aim of this study was to determine if neonatal PCB treatment increases adult testis weight and DSP. Treated rats received either Aroclor 1242 or 1254 (0.4-3.2 mg/day), from birth to Day 25 by daily injection; some treated litters also received T4 replacement. Controls received vehicle alone. Tritiated thymidine autoradiography was used to assess Sertoli cell proliferation in 15-day control and Aroclor-treated rats. Serum T4 was measured at 25, 45, and 135 days of age, and serum testosterone, testis weight, DSP, and testicular histology were examined at 135 days. Both Aroclor 1242 and 1254 suppressed serum T4 concentrations; Aroclor 1254 was more potent and long lasting. Testis weight was increased 22 and 13% in rats that received the 1.6 and 3.2 mg/day Aroclor 1242 doses, respectively, while the 0.4 mg/day dose did not produce significant increases. Aroclor 1254 produced significant increases in testis weight of 13 and 23% at the 0.4 and 1.6 mg/day doses, respectively. The 1.6 mg/day Aroclor 1242 and the 0.4 and 1.6 mg/day Aroclor 1254 doses increased DSP by 27, 11, and 42%, respectively; other treatments did not produce significant increases. At 15 days of age, Sertoli cell proliferation was greater in treated rats than in controls. T4 replacement decreased or eliminated the increased testis weight and DSP seen in Aroclor-treated rats. The highest dose of Aroclor 1242 and both doses of Aroclor 1254 decreased adult body weight, while other treatments did not. These results indicate that neonatal PCB treatment increases adult testis weight and DSP in rats. PCBs produce this effect primarily by inducing hypothyroidism, which leads to increased Sertoli cell proliferation, testis weight, and DSP. Thus PCBs, despite inhibitory effects on adult reproductive organs, can paradoxically stimulate increases in adult testis weight and DSP when administered neonatally. These data emphasize the pleiotropic nature of PCB effects and the susceptibility of the developing reproductive system to environmental factors.