Helicobacter infection decreases reproductive performance of IL10-deficient mice

Abstract

Infections with a variety of Helicobacter species have been documented in rodent research facilities, with variable effects on rodent health. Helicobacter typhlonius has been reported to cause enteric disease in immunodeficient and IL10(-/-) mice, whereas H. rodentium has only been reported to cause disease in immunodeficient mice coinfected with other Helicobacter species. The effect of Helicobacter infections on murine reproduction has not been well studied. The reproductive performance of C57BL/6 IL10(-/-) female mice intentionally infected with H. typhlonius, H. rodentium, or both was compared with that of age-matched uninfected controls or similarly infected mice that received antihelicobacter therapy. The presence of Helicobacter organisms in stool and relevant tissues was detected by PCR assays. Helicobacter infection of IL10(-/-) female mice markedly decreased pregnancy rates and pup survival. The number of pups surviving to weaning was greatest in noninfected mice and decreased for H. rodentium > H. typhlonius >> H. rodentium and H. typhlonius coinfected mice. Helicobacter organisms were detected by semiquantitative real-time PCR in the reproductive organs of a subset of infected mice. Treatment of infected mice with a 4-drug regimen consisting of amoxicillin, clarithromycin, metronidazole, and omeprazole increased pregnancy rates, and pup survival and dam fecundity improved. We conclude that infection with H. typhlonius, H. rodentium, or both decreased the reproductive performance of IL10(-/-) mice. In addition, antihelicobacter therapy improved fecundity and enhanced pup survival.

Figure 1.

Experimental design. Each experiment (Exp) consisted of 4 female mice in each of 4 groups (control [noninfected], H. rodentium-infected, H. typhlonius-infected, and H. rodentium- and H. typhlonius-coinfected). Mice were infected on day 0 (indicated by an asterisk), which serves as the reference for all date calculations, recorded as days postinfection. The point at which male mice were added is indicated by a white arrow; the point at which they were removed is indicated by a gray arrow. The duration of maternal treatment with the commercial diet containing antihelicobacter drugs is indicated by the black bar.

Figure 2.

Effect of Helicobacter infection on reproductive success in IL10⁻/⁻ mice. (A) Pregnancy rates for female mice that did not receive antihelicobacter therapy are shown as a function of infection status. (B) Pregnancy rates for female mice that received antihelicobacter treatment on day 31 and continued for the duration of the experiment, shown as a function of infection status. (C) The numbers of pups born (black bars) and surviving to weaning (white bars) are shown as a function of infection status for females that did not receive antihelicobacter therapy. (D) The numbers of pups born (black bars) and surviving to weaning (white bars) are shown as a function of infection status for female mice that received antihelicobacter therapy starting on day 31 postinfection for the duration of the study. *, P < 0.05 compared with value for noninfected control dams. CON, control (noninfected); R, infected with H. rodentium; T, infected with H. typhlonius; R + T, dually infected with H. rodentium and H. typhlonius.