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15 pages, 2180 KiB

Open AccessArticle

Transgenerational Transcriptomic and DNA Methylome Profiling of Mouse Fetal Testicular Germline and Somatic Cells after Exposure of Pregnant Mothers to Tributyltin, a Potent Obesogen

by Keiko Shioda, Junko Odajima, Bruce Blumberg and Toshi Shioda

Metabolites 2022, 12(2), 95; https://doi.org/10.3390/metabo12020095 - 20 Jan 2022

Cited by 4 | Viewed by 2295

Abstract

Obesogens such as tributyltin (TBT) are xenobiotic compounds that promote obesity, in part by distorting the normal balance of lipid metabolism. The obesogenic effects of TBT can be observed in directly exposed (F1 and F2 generations) and also subsequent generations (F3 and beyond) [...] Read more.

Obesogens such as tributyltin (TBT) are xenobiotic compounds that promote obesity, in part by distorting the normal balance of lipid metabolism. The obesogenic effects of TBT can be observed in directly exposed (F1 and F2 generations) and also subsequent generations (F3 and beyond) that were never exposed. To address the effects of TBT exposure on germ cells, we exposed pregnant transgenic OG2 mouse dams (F0), which specifically express EGFP in germline cells, to an environmentally relevant dose of TBT or DMSO throughout gestation through drinking water. When fed with a high-fat diet, F3 male offspring of TBT-exposed F0 dams (TBT-F3) accumulated much more body fat than did DMSO-F3 males. TBT-F3 males also lost more body fluid and lean compositions than did DMSO-F3 males. Expression of genes involved in transcriptional regulation or mesenchymal differentiation was up-regulated in somatic cells of TBT-F1 (but not TBT-F3) E18.5 fetal testes, and promoter-associated CpG islands were hyper-methylated in TBT-F1 somatic cells. Global mRNA expression of protein-coding genes in F1 or F3 fetal testicular cells was unaffected by F0 exposure to TBT; however, expression of a subset of endogenous retroviruses was significantly affected in F1 and F3. We infer that TBT may directly target testicular somatic cells in F1 testes to irreversibly affect epigenetic suppression of endogenous retroviruses in both germline and somatic cells. Full article

(This article belongs to the Special Issue Obesogens: Risks of Obesity and Metabolic Disease)

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Review

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8 pages, 3779 KiB

Open AccessReview

Obesogens in Children—An Uncharted Territory

by Mirjam Močnik and Nataša Marčun Varda

Metabolites 2021, 11(12), 882; https://doi.org/10.3390/metabo11120882 - 17 Dec 2021

Cited by 6 | Viewed by 2669

Abstract

Obesogens are exogenous chemicals belonging to the group of endocrine-disrupting chemicals and are believed to interfere in obesity development. In children, several chemicals are under investigation, most commonly bisphenol A, phthalates, perfluorinated alkyl substances, and persistent organic pollutants, including organochlorinated pesticides, tributyltin, polychlorinated [...] Read more.

Obesogens are exogenous chemicals belonging to the group of endocrine-disrupting chemicals and are believed to interfere in obesity development. In children, several chemicals are under investigation, most commonly bisphenol A, phthalates, perfluorinated alkyl substances, and persistent organic pollutants, including organochlorinated pesticides, tributyltin, polychlorinated biphenyls and dioxins. Several associations have been studied between chemical exposure in utero and postnatally. Current opinion among researchers indicates that the obesogen theory is very likely; however, limited published studies show inconsistent support for the obesogenic effects of most substances in children and are limited by difficulty in providing the exact mechanisms of action, nor is their mutual effect in humans known, let alone in children. Existing data indicate that we have only scratched the surface and have much more to learn about obesogens. Hopefully, in the future, more information will provide an opportunity for policy makers to take action and protect public health. Full article

(This article belongs to the Special Issue Obesogens: Risks of Obesity and Metabolic Disease)

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15 pages, 1043 KiB

Open AccessReview

Pesticides and Male Fertility: A Dangerous Crosstalk

by Sílvia Moreira, Sara C. Pereira, Vicente Seco-Rovira, Pedro F. Oliveira, Marco G. Alves and Maria de Lourdes Pereira

Metabolites 2021, 11(12), 799; https://doi.org/10.3390/metabo11120799 - 25 Nov 2021

Cited by 29 | Viewed by 3647

Abstract

In recent decades, an increasing incidence of male infertility has been reported. Interestingly, and considering that pesticides have been used for a long time, the high incidence of this pathological state is concomitant with the increasing use of these chemicals, suggesting they are [...] Read more.

In recent decades, an increasing incidence of male infertility has been reported. Interestingly, and considering that pesticides have been used for a long time, the high incidence of this pathological state is concomitant with the increasing use of these chemicals, suggesting they are contributors for the development of human infertility. Data from literature highlight the ability of certain pesticides and/or their metabolites to persist in the environment for long periods of time, as well as to bioaccumulate in the food chain, thus contributing for their chronic exposure. Furthermore, pesticides can act as endocrine disrupting chemicals (EDCs), interfering with the normal function of natural hormones (which are responsible for the regulation of the reproductive system), or even as obesogens, promoting obesity and associated comorbidities, like infertility. Several in vitro and in vivo studies have focused on the effects and possible mechanisms of action of these pesticides on the male reproductive system that cause sundry negative effects, even though through diverse mechanisms, but all may lead to infertility. In this review, we present an up-to-date overview and discussion of the effects, and the metabolic and molecular features of pesticides on somatic cells and germinal tissues that affect germ cell differentiation. Full article

(This article belongs to the Special Issue Obesogens: Risks of Obesity and Metabolic Disease)

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