Infertility in Murine Acute Trypanosoma cruzi Infection Is Associated with Inhibition of Pre-Implantation Embryo Development

Abstract

We previously showed that Trypanosoma cruzi acute infection induced infertility in a great proportion of female mice, which resulted from a defect taking place before implantation. In this study, we have analyzed every step of reproduction from mating to implantation to identify the most sensitive event. Our results show that mating, ovulation, fertilization, and first division of the zygote of infected mice take place normally compared with uninfected mice, indicating that the defect occurred after the two-cell stage. In vivo development of two-cell embryos to the blastocyst stage was indeed dramatically delayed; some embryos even arrested their development before having reached the eight-cell stage while others degenerated. The effect was less pronounced when embryos were allowed to develop in vitro, indicating that the infectious context of the mother plays a role in maintaining growth retardation. The delay of embryonic development was associated with insufficient divisions of the blastomeres and led to abnormal blastocyst outgrowth that may explain implantation failure. Inhibition of cell division was correlated with the maternal parasitemia. This work clearly shows that T. cruzi infection dramatically impedes embryonic development, offering a model for further in vivo studies of embryotrophic factors produced by the oviduct of infected females.