1. Academic Validation
  2. Alternariol exerts embryotoxic and immunotoxic effects on mouse blastocysts through ROS-mediated apoptotic processes

Alternariol exerts embryotoxic and immunotoxic effects on mouse blastocysts through ROS-mediated apoptotic processes

  • Toxicol Res (Camb). 2021 Jun 16;10(4):719-732. doi: 10.1093/toxres/tfab054.
Chien-Hsun Huang 1 Fu-Ting Wang 2 Wen-Hsiung Chan 3
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, Taoyuan General Hospital, Ministry of Health & Welfare, Taoyuan City 33004, Taiwan.
  • 2 Rehabilitation and Technical Aid Center, Taipei Veterans General Hospital, Taipei City 11217, Taiwan.
  • 3 Department of Bioscience Technology and Center for Nanotechnology, Chung Yuan Christian University, Chung Li District, Taoyuan City 32023, Taiwan.
Abstract

Alternariol (AOH), a mycotoxin belonging to the genus Alternaria, has been shown to induce cytotoxicity, including Apoptosis and cell cycle arrest, in several mammalian cell types. However, its effects on early-stage embryonic development require further investigation. Here, we have shown that AOH exerts embryotoxic effects on mouse blastocyst-stage embryos and long-term adverse effects on immunity in one-day-old newborn mice of the next generation. Significant Apoptosis and decrease in total cell number, predominantly through loss of inner cell mass (ICM), and to a minor extent, trophectoderm (TE) cells, were observed in AOH-treated blastocysts. Moreover, AOH exerted detrimental effects on pre- and post-implantation embryo development potential and induced a decrease in fetal weight in in vitro development and embryo transfer assays. Injection of pregnant mice with AOH (1, 3 and 5 mg/kg body weight/day) for 4 days resulted in Apoptosis of blastocyst-stage embryos and injurious effects on embryonic development from the zygote to blastocyst stage or embryo degradation and a further decrease in fetal weight. Furthermore, AOH exerted a long-term impact on the next generation, triggering a significant increase in total oxidative stress content and expression of genes encoding antioxidant proteins. Lower expression of CXCL1, IL-1β and IL-8 related to innate immunity was detected in liver tissue extracts obtained from one-day-old newborns of AOH-injected pregnant mice (5 mg/kg body weight/day) relative to their non-treated counterparts. In addition, ROS served as an upstream regulator of AOH-triggered apoptotic processes and impairment of embryonic development. Our collective results highlight the potential of AOH as an embryotoxic and immunotoxic risk factor during embryo and infant development stages in mice.

Keywords

alternariol; apoptosis; embryonic development; immunotoxicity; oxidative stress.

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