Acute reproductive toxicity of 3,3'-iminodipropionitrile in female rats

A potent neurotoxin 3,3'-iminodipropionitrile (IDPN), which is an occupational exposure hazard in industry, induces persistent behavioral abnormalities in experimental animals; however, its reproductive toxicity has not been determined. Therefore, we assessed the toxicity of IDPN in the reproductive system of female rats. A single intraperitoneal injection of IDPN (1000 mg/kg body weight) into female Wistar-Imamichi rats caused acute estrous cycle arrest at diestrus for up to 15 days. The arrest was accompanied by follicular atresia, and following arrest, the estrous cycle and ovarian morphology recovered. Ovarian mRNA levels of growth differentiation factor 9 and Fas ligand, a cell death marker, transiently increased following IDPN injection, but eventually they returned to basal levels. IDPN added to in vitro cultures of ovarian follicles also induced the expression of these genes, indicating that IDPN directly promoted ovarian cell death.