Levonorgestrel enhanced Toxoplasma gondii infection risk via progesterone receptor upregulation

The numerous stray cats and dogs worldwide pose a huge burden on local governments, keeping residents safe and healthy, and maintaining clean cities with good traffic situations. To effectively control the populations of these stray animals, while considering animal welfare, researchers have suggested the use of levonorgestrel (LNG) as a contraceptive method. However, the potential side effects of LNG on these animals need to be evaluated before widespread application. Since dogs and cats play important roles in the transmission of Toxoplasma gondii as intermediate and definitive hosts, respectively, it is critical to assess the safety of LNG from the perspective of its effect on Toxoplasma susceptibility. In this study, the susceptibility of mice to T. gondii infection was investigated in vivo and in vitro with the presence of LNG. As a result, LNG increased the risk of infection, which was probably associated with the downregulation of IFN-γ levels, but not with the alteration of host sex hormone levels. Concurrently, the presence of LNG enhanced the expression of its ligand, the progesterone receptor (PGR), on the host cells. The promotional effect of LNG on T. gondii infection was attenuated when the PGR gene was knocked down. This investigation represents the inaugural study of LNG's side effects on T. gondii infection in mice, underscoring the significance of choosing or developing suitable contraceptive drugs for stray animals.