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Toxicol Res. 2020 Feb 04;36(3):249-256. doi: 10.1007/s43188-019-00028-y. eCollection 2020 Jul.

Metabolic effects of exposure to pesticides during gestation in female Wistar rats and their offspring: a risk factor for diabetes?.

Toxicological research

Elvis Ngwa Ndonwi, Barbara Atogho-Tiedeu, Eric Lontchi-Yimagou, Tijjani S Shinkafi, Dieudonne Nanfa, Eric V Balti, Jean Claude Katte, Armand Mbanya, Tandi Matsha, Jean Claude Mbanya, Ali Shakir, Eugene Sobngwi

Affiliations

  1. Laboratory for Molecular Medicine and Metabolism, Biotechnology Center, University of Yaoundé 1, 3851 Yaoundé, Cameroon.
  2. Department of Biochemistry, Jamia Hamdard Deemed University, 110062 New Delhi, India.
  3. Faculty of Science, University of Yaounde 1, 812 Yaounde, Cameroon.
  4. Department of Biochemistry, Usmanu Danfodiyo University Sokoto, 2346 Sokoto, Nigeria.
  5. Diabetes Research and Training Center, Albert Einstein College of Medicine, 10461 Bronx, NY USA.
  6. Diabetes Research Center, Brussels Free University-VUB, Laarbeeklaan 101, 1090 Brussels, Belgium.
  7. National Obesity Centre, Yaoundé Central Hospital, 87, Yaoundé, Cameroon.
  8. Department of Biomedical Sciences, Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, Cape Town, 7535 South Africa.
  9. Department of Internal Medicine, Faculty of Medicine and Biomedical Sciences, University of Yaoundé 1, 1364 Yaoundé, Cameroon.

PMID: 32685429 PMCID: PMC7351921 DOI: 10.1007/s43188-019-00028-y

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.

© Korean Society of Toxicology 2020.

Keywords: Dyslipidemia; GLUT4; Hyperglycemia; NFkβ; Pesticide

Conflict of interest statement

Conflict of interestThe authors declare that there are no conflicts of interest.

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