title: Effects of ochratoxin a on mouse oocyte maturation and fertilization, and apoptosis during fetal development.
abstract: We previously reported that ochratoxin A (OTA), a mycotoxin found in many foods worldwide, causes nephrotoxicity, hepatotoxicity, and immunotoxicity, and is a risk factor for abnormal embryonic development. More specifically, OTA triggers apoptotic processes in the inner cell mass of mouse blastocysts, decreasing cell viability and embryonic development. In the current study, we investigated the deleterious effects of OTA on mouse oocyte maturation, in vitro fertilization (IVF), and subsequent pre- and postimplantation development both in vitro and in vivo. Notably, OTA significantly impaired mouse oocyte maturation, decreased IVF rates, and inhibited subsequent embryonic development in vitro. Preincubation of oocytes with OTA during in vitro maturation increased postimplantation embryonic resorption and decreased mouse fetal weight. In an in vivo animal model, provision of 1-10 μM OTA in the drinking water or intravenous injection of 1 or 2 mg/kg body weight of OTA decreased oocyte maturation and IVF, and had deleterious effects on early embryonic development. Importantly, preincubation of oocytes with a caspase-3-specific inhibitor effectively blocked these OTA-triggered deleterious effects, suggesting that the embryonic injury induced by OTA is mediated via a caspase-dependent apoptotic mechanism. Furthermore, OTA upregulated the levels of p53 and p21 in blastocyst cells derived from OTA-pretreated oocytes, indicating that such cells undergo apoptosis via p53-, p21-, and caspase-3-dependent regulatory mechanisms. This could have deleterious effects on embryonic implantation and fetal survival rates, as seen in our animal models. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 724-735, 2016.
authors.affiliation: Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.|Chang Gung University School of Medicine, Kaohsiung, Taiwan.
authors.forename: Fu-Jen
authors.initials: FJ
authors.lastname: Huang
authors.affiliation: Department of Bioscience Technology and Center for Nanotechnology, Chung Yuan Christian University, Chung Li, Taiwan.|Center for Biomedical Technology, Chung Yuan Christian University, Chung Li, Taiwan.
authors.forename: Wen-Hsiung
authors.initials: WH
authors.lastname: Chan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002273:Carcinogens / Q000633:toxicity*; D047108:Embryonic Development / Q000187:drug effects; D005260:Female; D005306:Fertilization / Q000187:drug effects*; D005307:Fertilization in Vitro; D051379:Mice; D008813:Mice, Inbred ICR; D009793:Ochratoxins / Q000633:toxicity*; D009865:Oocytes / Q000166:cytology / Q000187:drug effects*
chemical_list: D002273:Carcinogens; D009793:Ochratoxins; C025589:ochratoxin A
keywords: apoptosis; embryonic development; ochratoxin A; oocyte maturation