Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Metabolic effects of exposure to pesticides during gestation in female Wistar rats and their offspring: a risk factor for diabetes?

  • Ndonwi, Elvis Ngwa (Laboratory for Molecular Medicine and Metabolism, Biotechnology Center, University of Yaounde) ;
  • Atogho-Tiedeu, Barbara (Laboratory for Molecular Medicine and Metabolism, Biotechnology Center, University of Yaounde) ;
  • Lontchi-Yimagou, Eric (Department of Biochemistry, Usmanu Danfodiyo University) ;
  • Shinkaf, Tijjani S. (Faculty of Science, University of Yaounde) ;
  • Nanfa, Dieudonne (Laboratory for Molecular Medicine and Metabolism, Biotechnology Center, University of Yaounde) ;
  • Balti, Eric V. (Diabetes Research Center, Brussels Free University-VUB) ;
  • Katte, Jean Claude (National Obesity Centre, Yaounde Central Hospital) ;
  • Mbanya, Armand (Department of Biochemistry, Usmanu Danfodiyo University) ;
  • Matsha, Tandi (Department of Biomedical Sciences, Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology) ;
  • Mbanya, Jean Claude (Laboratory for Molecular Medicine and Metabolism, Biotechnology Center, University of Yaounde) ;
  • Shakir, Ali (Faculty of Science, University of Yaounde) ;
  • Sobngwi, Eugene (Laboratory for Molecular Medicine and Metabolism, Biotechnology Center, University of Yaounde)
  • Received : 2019.03.04
  • Accepted : 2019.10.18
  • Published : 2020.07.15
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Abstract

Some pesticides increase the risk of type 2 diabetes, but whether fetal exposure carries transgenerational risk remains unknown. We evaluated the metabolic effects of gestational exposure to chlorpyrifos and imidacloprid in female Wistar rats and their offspring. We studied female nulliparous Wistar rats, including six exposed to imidacloprid (IMI) and six to chlorpyrifos (CPF) once daily throughout gestation at 1/10 lethal dose 50, while six (control group) received distilled water. These were explored 1 month after the birth of the offspring, while their offspring were explored at weaning (4 weeks) and adult age (12 weeks). Blood glucose, insulin and lipid profile were determined at each stage, while glucose transporter 4 (GLUT4) and nuclear factor kappa beta (NFkβ) protein expression was measured in skeletal muscle at the end of follow up. Exposure to pesticides was associated with significantly higher fasting glucose (+25.4 to 30.9%) and insulin (> 100%) levels, with > 100% increased insulin resistance (HOMA-IR), -18.3 to -21.1% reduced HDL-cholesterol and +60.9 to +102.6% increased LDL-cholesterol in mothers. GLUT4 expression was reduced by 28.9-42.3% while NFkβ expression increased by 32.8-35.4% in mothers. In offspring, similar abnormalities were observed at weaning (+18.4 to 67.4% fasting glucose, +57.1 to 72.2% LDL-cholesterol, +72.3 to 78.2% fasting insulin), persisting at adult age with decreased expression of GLUT4 (-52.8 to 54.5%) and increased expression of NFkβ (+30.5 to 30.7%). Gestational exposure to imidacloprid and chlorpyrifos induces hyperglycemia, insulin resistance and dyslipidemia in female Wistar rats and their offspring. The effects on offspring persist until adult age, suggesting intergenerational adverse effects.

Keywords

Acknowledgement

The authors express gratitude to the International Center for Genetic Engineering and Biotechnology (ICGEB) for financial support that enabled the realization of this work. Our appreciation goes to the Jamia Hamdard University (Department of Biochemistry and Animal Facility) for the provision of space and equipment.

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