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Prolonged atrazine exposure beginning in utero and adult uterine morphology in mice

Published online by Cambridge University Press:  30 March 2021

Meaghan J. Griffiths Open the ORCID record for Meaghan J. Griffiths [Opens in a new window] ,
Amy L. Winship Open the ORCID record for Amy L. Winship [Opens in a new window] ,
Jessica M. Stringer Open the ORCID record for Jessica M. Stringer [Opens in a new window] ,
Elyse O. Swindells ,
Alesia P. Harper ,
Bethany J. Finger ,
Karla J. Hutt Open the ORCID record for Karla J. Hutt [Opens in a new window]  and
Mark P. Green Open the ORCID record for Mark P. Green [Opens in a new window]
Meaghan J. Griffiths
Affiliation:
Development and Stem Cells Program, Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash University, Clayton, Australia
Amy L. Winship
Affiliation:
Development and Stem Cells Program, Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash University, Clayton, Australia
Jessica M. Stringer
Affiliation:
Development and Stem Cells Program, Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash University, Clayton, Australia
Elyse O. Swindells
Affiliation:
Development and Stem Cells Program, Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash University, Clayton, Australia
Alesia P. Harper
Affiliation:
School of BioSciences, University of Melbourne, Parkville, Australia
Bethany J. Finger
Affiliation:
School of BioSciences, University of Melbourne, Parkville, Australia
Karla J. Hutt
Affiliation:
Development and Stem Cells Program, Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash University, Clayton, Australia
Mark P. Green*
Affiliation:
School of BioSciences, University of Melbourne, Parkville, Australia
*
Address for correspondence: Dr Mark Green, School of BioSciences, University of Melbourne, Parkville, Melbourne, VIC 3010, Australia. Email: mark.green@unimelb.edu.au
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Abstract

Through drinking water, humans are commonly exposed to atrazine, a herbicide that acts as an endocrine and metabolic disruptor. It interferes with steroidogenesis, including promoting oestrogen production and altering cell metabolism. However, its precise impact on uterine development remains unknown. This study aimed to determine the effect of prolonged atrazine exposure on the uterus. Pregnant mice (n = 5/group) received 5 mg/kg body weight/day atrazine or DMSO in drinking water from gestational day 9.5 until weaning. Offspring continued to be exposed until 3 or 6 months of age (n = 5–9/group), when uteri were collected for morphological and molecular analyses and steroid quantification. Endometrial hyperplasia and leiomyoma were evident in the uteri of atrazine-exposed mice. Uterine oestrogen concentration, oestrogen receptor expression, and localisation were similar between groups, at both ages (P > 0.1). The expression and localisation of key epithelial-to-mesenchymal transition (EMT) genes and proteins, critical for tumourigenesis, remained unchanged between treatments, at both ages (P > 0.1). Hence, oestrogen-mediated changes to established EMT markers do not appear to underlie abnormal uterine morphology evident in atrazine exposure mice. This is the first report of abnormal uterine morphology following prolonged atrazine exposure starting in utero, it is likely that the abnormalities identified would negatively affect female fertility, although mechanisms remain unknown and require further study.

Keywords

Endocrine-disrupting chemicalatrazineendometriumuterusoestrogen
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 13 , Issue 1 , February 2022 , pp. 39 - 48
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Copyright
© The Author(s), 2021. Published by Cambridge University Press in association with International Society for Developmental Origins of Health and Disease

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