The obesogen tributyltin induces abnormal ovarian adipogenesis in adult female rats
Abstract
Tributyltin chloride (TBT) is an obesogen associated with various metabolic and reproductive dysfunctions after in utero exposure. However, few studies have evaluated TBT's obesogenic effect on adult ovaries. In this study, we assessed whether TBT's obesogenic effects resulted in adult ovarian adipogenesis and other reproductive abnormalities. TBT was administered to adult female Wistar rats, and their reproductive tract morphophysiology was assessed. We further assessed the ovarian mRNA/protein expression of genes that regulate adipogenesis. Rats exposed to TBT displayed abnormal estrous cyclicity, ovarian sex hormone levels, ovarian follicular development and ovarian steroidogenic enzyme regulation. Rats exposed to TBT also demonstrated abnormal ovarian adipogenesis with increased cholesterol levels, lipid accumulation, and PPARγ, C/EBP-β and Lipin-1 expression. A negative correlation between the ovarian PPARγ expression and aromatase expression was observed in the TBT rats. Furthermore, TBT exposure resulted in reproductive tract atrophy, inflammation, oxidative stress and fibrosis. Ovarian dysfunctions also co-occurred with the uterine irregularities. Abnormal ovarian adipogenic markers occurring after TBT exposure may be associated with uterine irregularities. A positive correlation between the ovarian cholesterol levels and uterine inflammation was observed in the TBT rats. These findings suggest that TBT leads to ovarian obesogenic effects directly by abnormal adipogenesis and/or indirectly through adult reproductive tract irregularities.
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Prenatal exposure to androgenic EDC (triclosan, glyphosate, tributyltin, nicotine) is of increasing concern, given the suspected epigenetic role of in utero androgen exposure in the pathogenesis of PCOS.
“Prenatal exposure to androgenic EDC (triclosan, glyphosate, tributyltin, nicotine) is of increasing concern, given the suspected epigenetic role of in utero androgen exposure in the pathogenesis of PCOS [48,200,201].”
From Polycystic Ovary Syndrome: An Evolutionary Adaptation to Lifestyle and the Environment (2022) · cites this paper as [200]
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Polycystic Ovarian Syndrome: Correlation Between Hyperandrogenism, Insulin Resistance and Obesity.
Zeng, X., Xie, Y.-J., Liu, Y.-T., Long, S.-L., & Mo, Z.-C. (2020) · Clinica Chimica Acta · doi:10.1016/j.cca.2019.11.003 · Cited by 525 · see citing works
Polycystic Ovary Syndrome: An Evolutionary Adaptation to Lifestyle and the Environment
parker, J., O'Brien, C., Hawrelak, J., & Gersh, F. (2021) · doi:10.20944/preprints202112.0088.v1 · Cited by 113 · see citing works
Polycystic Ovary Syndrome: An Evolutionary Adaptation to Lifestyle and the Environment
Parker, J., O’Brien, C., Hawrelak, J., & Gersh, F. L. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph19031336 · Cited by 114 · see citing works
“So far, about 50 obesogens have been recognized including tributyltin, parabins, DDT, cadmium, persistent organic pollutants and many others (202,222,223).”
Background
- Authors
- de Araújo, J. F. P., Podratz, P. L., Sena, G. C., Merlo, E., Freitas-Lima, L. C., Ayub, J. G. M., Pereira, A. F. Z., Santos-Silva, A. P., Miranda-Alves, L., Silva, I. V., & Graceli, J. B.
- Affiliations
- Universidade Federal do Espírito Santo (BR)
- Universidade Federal do Rio de Janeiro (BR)
- Corresponding author
- Graceli, Jones B.
- Venue
- Toxicology Letters
- Publisher
- Elsevier BV
- Published
- 2018-10
- Volume
- 295
- Pages
- 99-114
- ISSN
- 0378-4274 (ISSN-L)
- OpenAlex
- W2808149145
- Cited by
- 65
- References
- 0
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 10 · 2023: 5 · 2022: 7 · 2021: 12 · 2020: 11 · 2019: 7 · 2018: 2
- FWCI
- 3.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Toxicology Letters (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Keywords
- tributyltin chloride, obesogens, ovarian dysfunction, estrous cyclicity, aromatase, PPARγ, C/EBPβ, LPIN1, cholesterol accumulation, ovarian steroidogenesis, metritis, oxidative stress, uterine fibrosis, endocrine disruptors
- MeSH terms
- Steroidogenic Acute Regulatory Protein, Adipose Tissue, Pelvic Inflammatory Disease, Animals, Atrophy, Cholesterol, Cholesterol Side-Chain Cleavage Enzyme, Environmental Pollutants, Female, Fibrosis, Ovarian Follicle, Obesity, Ovary, Phosphoproteins, RNA, Messenger, Gonadal Steroid Hormones, Trialkyltin Compounds, Gene Expression Regulation, Enzymologic, Rats, Wistar, Oxidative Stress, Estrous Cycle, Adiposity, Adipogenesis, Lipid Droplets
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