Schistosoma mansoni: Susceptibility Differences between Male and Female Mice Can Be Mediated by Testosterone during Early Infection MASATOSHI NAKAZAWA,* MARCELO R. FANTAPPIE,† GEORGE L. FREEMAN,JR.,* SILVANA ELOI-SANTOS,‡ NANCY J. OLSEN,§ W. J. KOVACS,§ W. EVAN SECOR,* AND DANIEL G. COLLEY* *Division of Parasitic Disease, Centers for Disease Control and Prevention, Public Health Service, U.S. Department of Health and Human Services, Atlanta, Georgia, 30341, U.S.A.; †Departamento de Bioqı ´mica Me ´dica, Instituto de Cie ˆncias Biome ´dicas, Universidade Federal do Rio de Janiero, Brazil; ‡Departamento de Propede `utica Complementar, Faculdade de Medicina, Universidade Federal de Minas Gerais, 30.130.100, Belo Horizonte, Brazil; and §Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, 37232, U.S.A. NAKAZAWA, M., FANTAPPIE, M. R., FREEMAN, G. L., JR., ELOI-SANTOS, S., OLSEN, N. J., KOVACS, W. J., SECOR, W. E., AND COLLEY, D. G. 1997. Schistosoma mansoni: Susceptibility differences between male and female mice can be mediated by testosterone during early infection. Experimental Parasitology 85, 233–240. In murine Schistosoma mansoni infections, fewer adult worms develop in male than in female mice infected with the same number of cercariae. To evaluate a potential role for testosterone in this phenomenon, testosterone levels were manipulated in groups of CBA/J mice that were then infected and monitored for survival rates, worm burdens, organomegaly, and egg produc- tion. By 16 weeks of infection, more than 80% of mice in groups with low levels of testosterone (untreated females, castrated males, or carrier-treated castrates) were dead, while less than 40% of those in groups with high levels of testosterone (sham-castrated males, testosterone-treated castrates, or testosterone-treated female mice) succumbed to infection. The mean number of worms recovered from mice in the low testosterone level groups was comparable among groups, and significantly greater than that from those in high-testosterone-level groups. The degree of organomegaly observed correlated strongly with worm burden, but the number of hepatic eggs per female worm did not differ significantly between groups. When male mice were castrated or sham-castrated 5 weeks after S. mansoni infection, no significant differences in host survival occurred. Furthermore, female mice treated with testosterone demonstrated reduced worm burdens if the testosterone was given 10 days prior to infection but not if the testosterone was given 10 days or 5 weeks after infection. Thus, the host sex bias observed in parallel-infected male and female mice appears to be related to the presence of male gonadal tissue or testosterone early in infection, during the development of immature schistosomules. INDEX DESCRIPTORS AND ABBREVIATIONS: Schistosoma mansoni; Schistosomiasis; Host gender differences; Susceptibility; Trematode; Testosterone; Analysis of variance (ANOVA); Low- testosterone (LT); High-testosterone (HT). INTRODUCTION The relationship between host gender and susceptibility to parasitic infection has been studied in a variety of host–parasite combina- tions (reviewed in Solomon 1969; Goble and Konopka 1973). In general, males develop more severe infections with larger parasite burdens than do females. However, in experimental Schistosoma mansoni infections, the opposite phenomenon occurs (Eloi-Santos et al. 1992). When male and female mice of inbred CBA/J and C57BL/6 strains, and outbred CF1 mice were exposed subcutaneously to equal numbers of S. mansoni cercariae, significantly more adult worms were recovered from female mice than from male mice. Furthermore, by 16 weeks of infection, significantly more female than male mice had died from infection. We now extend these observations with the demonstra- tion that worm burden and host longevity dur- ing experimental S. mansoni infection is related to the presence of testosterone in the host early during infection. MATERIALS AND METHODS Male and female 6- to 8-week-old CBA/J mice (Jackson Laboratories, Bar Harbor, ME) were maintained in the EXPERIMENTAL PARASITOLOGY 85, 233–240 (1997) ARTICLE NO. PR974148 233 0014-4894/97