Helicobacter Infection Significantly Alters Pregnancy Success in Laboratory Mice

Abstract

Helicobacter spp. are gram-negative, helically shaped bacteria that cause gastric and enterohepatic infections in mammalian species. Although Helicobacter infection frequently is implicated to interfere with reproductive success, few experimental data support these claims. We therefore retrospectively investigated the effect of Helicobacter infection on murine pregnancy outcome after the identification of endemic Helicobacter infection in an animal research facility. Multiplex conventional PCR analysis was used to characterize Helicobacter infection status in one inbred and 2 transgenic strains of mice in 2 self-contained rooms assigned to the same investigator. Outcomes of timed-mating experiments were compared among Helicobacter spp.-infected and uninfected mice of the same strain; Helicobacter infection was eradicated from the colony through fostering with uninfected dams. Although Helicobacter infection affected fecundity in only one strain of transgenic mouse, the total number of embryos per gravid uterus was significantly reduced in C57BL/6J mice that were infected with a single Helicobacter species, H. typhlonius. Helicobacter infection was also associated with a significant increase in the number of resorbing embryos per uterus and significant decreases in pregnancy-associated weight gain relative to uninfected mice in C57BL6/J mice and one transgenic strain. Helicobacter spp.-infected mice of all tested strains exhibited higher frequency of intrauterine hemorrhaging relative to uninfected mice. These results indicate that naturally-acquired Helicobacter infection not only reduces the productivity of a research animal breeding colony, but also negatively impacts embryo health. Despite these deleterious effects, these data suggest that colonies can be rederived to be Helicobacter-free by Cesarean section and fostering with uninfected dams. This paper provides the first evidence that H. typhlonius infection is sufficient to interfere with reproductive success and embryo health of C57BL/6J mice. Animal research facilities should therefore implement Helicobacter spp. surveillance and control practices to avoid confounding experimental results and to improve breeding colony efficiency.

Figure 1.

Helicobacter infection significantly affects pregnancy-associated weight gain (%, relative to baseline) but does not induce maternal anemia. Pregnant mice were weighed on GD0 and GD6 through GD12. Helicobacter infection significantly reduced weight gain in (A) C57BL/6 and (C) LysMCre⁺ but not (B) LysMCre^– mice. Hct (%) was largely unaffected by the presence or absence of Helicobacter infection in these strains. Data are presented as mean ± SEM (n = 4 mice per group). *, P < 0.05; †, P < 0.01; ‡, P < 0.001.

Figure 2.

Helicobacter spp. negatively affects midgestational embryo health. Gross pathologic view of (A and B) C57BL/6J, (C and D) LysMCre^–, and (E and F) LysMCre⁺ uteri of (A, C, and E) Helicobacter-infected and (B, D, and F) uninfected mice. Macroscopic evaluation of uteri revealed a significant increase in intrauterine hemorrhage (small white arrows) in Helicobacter spp.-infected C57BL/6J, LysMCre^–, and LysMCre⁺ mice relative to uninfected mice of the same strain (quantified in Table 3). Helicobacter-infected C57BL/6J and LysMCre⁺ mice exhibited significantly greater numbers of resorbing embryos (white arrowheads) than did uninfected mice of these strains (Table 3).