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

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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.

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Abbreviations

ACh:

Acetylcholine

ANOVA:

Analysis of variance

CPF:

Chloropyrifos

EDTA:

Ethylene diamine tetra-acetic acid

ELISA:

Enzyme-linked immuno-sorbent assay

EC:

Emulsifiable concentrate

FBG:

Fasting blood glucose

GLUT4:

Glucose transporter-4

HDL:

High density lipoprotein

HOMA-IR:

Homeostasis model assessment of insulin resistance

HOMA-β:

Homeostasis model assessment of beta cell function

ICGEB:

International Center for Genetic Engineering and Biotechnology

IMI:

Imidacloprid

LDL:

Low density lipoprotein

NFkβ:

Nuclear factor kappa beta

PBST:

Phosphate buffered saline tween

SEM:

Standard error of mean

TC:

Total cholesterol

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Acknowledgements

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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Authors and Affiliations

  1. Laboratory for Molecular Medicine and Metabolism, Biotechnology Center, University of Yaoundé 1, 3851, Yaoundé, Cameroon

    Elvis Ngwa Ndonwi, Barbara Atogho-Tiedeu, Dieudonne Nanfa, Jean Claude Mbanya & Eugene Sobngwi

  2. Department of Biochemistry, Jamia Hamdard Deemed University, 110062, New Delhi, India

    Elvis Ngwa Ndonwi, Barbara Atogho-Tiedeu, Dieudonne Nanfa, Jean Claude Mbanya & Eugene Sobngwi

  3. Faculty of Science, University of Yaounde 1, 812, Yaounde, Cameroon

    Elvis Ngwa Ndonwi, Tijjani S. Shinkafi & Ali Shakir

  4. Department of Biochemistry, Usmanu Danfodiyo University Sokoto, 2346, Sokoto, Nigeria

    Eric Lontchi-Yimagou & Armand Mbanya

  5. Diabetes Research and Training Center, Albert Einstein College of Medicine, 10461, Bronx, NY, USA

    Tijjani S. Shinkafi

  6. Diabetes Research Center, Brussels Free University-VUB, Laarbeeklaan 101, 1090, Brussels, Belgium

    Eric V. Balti

  7. National Obesity Centre, Yaoundé Central Hospital, 87, Yaoundé, Cameroon

    Jean Claude Katte

  8. Department of Biomedical Sciences, Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, Cape Town, 7535, South Africa

    Tandi Matsha

  9. Department of Internal Medicine, Faculty of Medicine and Biomedical Sciences, University of Yaoundé 1, 1364, Yaoundé, Cameroon

    Jean Claude Mbanya & Eugene Sobngwi

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  1. Elvis Ngwa Ndonwi
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  2. Barbara Atogho-Tiedeu
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  7. Jean Claude Katte
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  8. Armand Mbanya
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  9. Tandi Matsha
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  10. Jean Claude Mbanya
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  12. Eugene Sobngwi
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Correspondence to Elvis Ngwa Ndonwi.

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Ndonwi, E.N., Atogho-Tiedeu, B., Lontchi-Yimagou, E. et al. Metabolic effects of exposure to pesticides during gestation in female Wistar rats and their offspring: a risk factor for diabetes?. Toxicol Res. 36, 249–256 (2020). https://doi.org/10.1007/s43188-019-00028-y

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  • DOI: https://doi.org/10.1007/s43188-019-00028-y

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