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DJ-1, a target protein for an endocrine disrupter, participates in the fertilization in mice
Masahiko Okada1, Ken-ichi Matsumoto, Takeshi Niki
1Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Abstract:
DJ-1 was first identified as an activated ras-dependent oncogene product and was later also found to be an infertility-related protein affected by sperm toxicants such as ornidazole (OR) and epichlorohydrin. These findings suggest that DJ-1 has functions in both somatic cells and sperm. In this study, to determine the relationship between DJ-1 and an endocrine disrupter and to determine the functions of DJ-1 in sperm, in vitro fertilization experiments were carried out using eggs and sperm extracted from mice that had or had not been treated with OR. We found that the amount of DJ-1 in sperm and the efficiency of fertilization decreased with the increasing dose of OR to which the mice were exposed. The addition of an anti-mouse DJ-1 serum to sperm solution before the in vitro fertilization reaction with eggs resulted in a decrease in the efficiency of fertilization to about one-third of that when pre-immune serum was added to sperm solution, indicating that DJ-1 participates in the fertilization.
Insights
DJ-1 protein levels in sperm and fertilization rates decline with exposure to the endocrine disruptor ornidazole (OR). DJ-1 is crucial for successful fertilization, as blocking it significantly reduces fertilization efficiency.
Area of Science:
- Reproductive biology
- Endocrinology
- Biochemistry
Background:
- DJ-1, initially identified as a ras-dependent oncogene product, is also implicated in infertility.
- Exposure to sperm toxicants like ornidazole (OR) affects DJ-1, suggesting its role in both somatic cells and sperm.
- Endocrine disruptors pose a significant threat to reproductive health.
Purpose of the Study:
- To investigate the relationship between DJ-1 and endocrine disruptors.
- To elucidate the specific functions of DJ-1 in sperm.
- To assess the impact of ornidazole exposure on DJ-1 levels and fertilization.
Main Methods:
- In vitro fertilization (IVF) experiments were conducted using mouse eggs and sperm.
- Mice were exposed to varying doses of ornidazole (OR) prior to sperm and egg extraction.
- Fertilization efficiency was measured, and the effect of anti-mouse DJ-1 serum on IVF was assessed.
Main Results:
- A dose-dependent decrease in both DJ-1 protein levels in sperm and fertilization efficiency was observed with increasing OR exposure.
- Addition of anti-mouse DJ-1 serum to sperm significantly reduced fertilization efficiency by approximately two-thirds compared to pre-immune serum.
- These findings demonstrate a direct correlation between OR exposure, DJ-1 levels, and sperm function.
Conclusions:
- DJ-1 plays a critical role in the process of mammalian fertilization.
- Endocrine disruptors like ornidazole can impair fertility by reducing DJ-1 levels in sperm.
- DJ-1 is a key mediator in sperm's response to environmental toxicants and is essential for reproductive success.