Impaired Morphogenesis and Function of Rat Adrenal Zona Glomerulosa by Developmental Low-Dose Exposure to DDT Is Associated with Altered Oct4 Expression.

Nataliya V Yaglova,Tatiana A Lomanovskaya,Elizaveta V Chereshneva,Elina S Tsomartova,Svetlana V Nazimova,Marina Y Ivanova,Valentin V Yaglov,Sergey S Obernikhin,Dibakhan A Tsomartova

doi:10.3390/ijms22126324

Nataliya V Yaglova, Tatiana A Lomanovskaya + Show 7 more

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https://doi.org/10.3390/ijms22126324

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Abstract

Dichlorodiphenyltrichloroethane (DDT) is a persistent organic pollutant and one of the most widespread endocrine disrupting chemicals. The impact of low-dose exposure to DDT on the morphogenesis of the adrenal gland is still poorly understood. The development and function of zona glomerulosa in rats has been found to be associated with changes in the expression of the transcription factor Oct4 (Octamer 4), which is the most important player in cell pluripotency. The aim of the study was to investigate the morphogenesis and function of rat adrenal zona glomerulosa in rats exposed to low doses of DDT during prenatal and postnatal development and to determine the possible role of Oct4 in DDT-mediated structural and functional changes. The DDT-exposed rats demonstrated slower development and lower functional activity of the zona glomerulosa during the pubertal period associated with higher expression of Oct4. Further, accelerated growth and restoration of hormone production was associated with, firstly, a decrease in Oct4 expressing cells and secondly, the loss of the inverse relationship between basal aldosterone levels and the number of Oct4 expressing cells. Thus, the transcriptional factor Oct4 exhibited an altered pattern of expression in the DDT-exposed rats during postnatal development. The results of the study uncover a novel putative mechanism by which low doses of DDT disrupt the development of adrenal zona glomerulosa.

Highlights

Incidences of endocrine-related disorders and associated somatic diseases have been increasing in recent decades
We found downregulation of canonical Wnt-signaling in the adrenal cortical cells, which was most pronounced in the zona glomerulosa during postnatal development in rats exposed to low doses of DDT [24]
The present study aimed to evaluate postnatal morphogenesis and the function of the adrenal zona glomerulosa in rats exposed to low doses of DDT during prenatal and postnatal development and aimed to elucidate the implication of the transcription factor Oct4 in the endocrine disruption of the development of the zona glomerulosa and hormone production

Summary

Introduction

Incidences of endocrine-related disorders and associated somatic diseases have been increasing in recent decades. According to the World Health Organization, endocrine disrupting chemicals are substances that alter one or more functions of the endocrine system and cause adverse health effects in an intact organism, or its progeny, or (sub)populations [1]. The Endocrine Society was the first to draw attention to the endocrine disrupters, considering them a novel direction for scientific investigations [2]. Since the first Scientific Statement of the Endocrine Society in 2009, data on animal and human studies have demonstrated the harmful effects of endocrine disrupters on the function and development of an organism [3,4,5,6]. Large-scale investigations on the impact of endocrine disrupters on morphogenetic processes, prenatal and postnatal histogenesis and organogenesis are required to decipher the mechanisms of congenital and developmental disorders and to revisit our knowledge on endocrine regulation of metabolism

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