Induction of infertility by the Chlamydia trachomatis mouse pneumonitis biovar in strains of mice that differ in their response to the 60 kDa heat shock protein

in Reproduction
Authors:
A. Khamesipour
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S. Pal
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E. M. Peterson
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L. M. de la Maza
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To determine the role that the host response to the chlamydial 60 kDa heat shock protein (hsp) plays in the pathogenesis of infertility, C3H/HeN (H-2k) and C57BL/6 (H-2b) mice were inoculated in the left ovarian bursa with 1 × 105 inclusion forming units of the Chlamydia trachomatis mouse pneumonitis (MoPn) biovar, and in the right ovarian bursa with mock-infected HeLa-229 cell extracts. Control mice were inoculated with mock-infected HeLa-229 cell extracts. These two strains of mice were chosen because the C3H mice mount a strong immune response to the 60 kDa hsp, whereas the C57BL/6 mice respond only weakly. Vaginal cultures obtained after inoculation were positive for 4 weeks in both strains of mice. Histological sections showed a marked acute inflammatory infiltrate that permeated all the layers of the oviduct and lasted for approximately 2 weeks in both strains. By the third week, mononuclear inflammatory cells were also observed and from 4 weeks after inoculation, hydrosalpinx formation was observed, particularly in the C3H mice. An inclusion immunofluorescence assay detected antibodies specific for chlamydia in the serum and the vaginal washes of the C3H and C57BL/6 mice. Western blot analysis of the serum samples showed an immune response to lipopolysaccharide, and the 30, 40 (major outer membrane protein) and 60 kDa cysteine-rich protein in both strains of mice. In addition, in the C3H mice a strong immune reaction was mounted against a 50 kDa component and the 60 kDa hsp. Six weeks after inoculation, the female mice were mated with male mice of proven fertility and the outcome of the pregnancies evaluated. Of the mock-infected C3H and C57BL/6 mice, 73% and 82% were bilaterally pregnant, respectively. In contrast, only 8% of the C3H and 25% of the C57BL/6 mice inoculated with the C. trachomatis MoPn were bilaterally pregnant (P<0.05). Furthermore, there were significantly fewer embryos in the right and left uterine horns of C3H mice in the animals inoculated with C. trachomatis than in controls, whereas in the C57BL/6 mice there were fewer embryos only in the left uterine horn. In conclusion, inoculation of the C. trachomatis MoPn into the ovarian bursa results in infertility in both the C3H and C57BL/6 mice. However, the effect was greater in the C3H mice than in the C57BL/6 mice.

 

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