Developmental Programming: Impact of Prenatal Exposure to Bisphenol A on Senescence and Circadian Mediators in the Liver of Sheep
Prenatal exposure to endocrine disruptors such as bisphenol A (BPA) plays a critical role in the developmental programming of liver dysfunction that is characteristic of nonalcoholic fatty liver disease (NAFLD). Circadian and aging processes have been implicated in the pathogenesis of NAFLD. We hypo...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-12-01
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| Series: | Toxics |
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| Online Access: | https://www.mdpi.com/2305-6304/12/1/15 |
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| author | Giuliana Motta Soundara Viveka Thangaraj Vasantha Padmanabhan |
| author_facet | Giuliana Motta Soundara Viveka Thangaraj Vasantha Padmanabhan |
| author_sort | Giuliana Motta |
| collection | DOAJ |
| description | Prenatal exposure to endocrine disruptors such as bisphenol A (BPA) plays a critical role in the developmental programming of liver dysfunction that is characteristic of nonalcoholic fatty liver disease (NAFLD). Circadian and aging processes have been implicated in the pathogenesis of NAFLD. We hypothesized that the prenatal BPA-induced fatty-liver phenotype of female sheep is associated with premature hepatic senescence and disruption in circadian clock genes. The expression of circadian rhythm and aging-associated genes, along with other markers of senescence such as telomere length, mitochondrial DNA copy number, and lipofuscin accumulation, were evaluated in the liver tissue of control and prenatal BPA groups. Prenatal BPA exposure significantly elevated the expression of aging-associated genes <i>GLB1</i> and <i>CISD2</i> and induced large magnitude differences in the expression of other aging genes—<i>APOE</i>, <i>HGF</i>, <i>KLOTHO,</i> and the clock genes <i>PER2</i> and <i>CLOCK</i>—in the liver; the other senescence markers remained unaffected. Prenatal BPA-programmed aging-related transcriptional changes in the liver may contribute to pathological changes in liver function, elucidating the involvement of aging genes in the pathogenesis of liver steatosis. |
| first_indexed | 2024-03-08T10:34:02Z |
| format | Article |
| id | doaj.art-06bcda6594af4f19a2c5a59df5b33d50 |
| institution | Directory Open Access Journal |
| issn | 2305-6304 |
| language | English |
| last_indexed | 2024-03-08T10:34:02Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxics |
| spelling | doaj.art-06bcda6594af4f19a2c5a59df5b33d502024-01-26T18:40:54ZengMDPI AGToxics2305-63042023-12-011211510.3390/toxics12010015Developmental Programming: Impact of Prenatal Exposure to Bisphenol A on Senescence and Circadian Mediators in the Liver of SheepGiuliana Motta0Soundara Viveka Thangaraj1Vasantha Padmanabhan2Department of Pediatrics, University of Michigan, Ann Arbor, MI 48105, USADepartment of Pediatrics, University of Michigan, Ann Arbor, MI 48105, USADepartment of Pediatrics, University of Michigan, Ann Arbor, MI 48105, USAPrenatal exposure to endocrine disruptors such as bisphenol A (BPA) plays a critical role in the developmental programming of liver dysfunction that is characteristic of nonalcoholic fatty liver disease (NAFLD). Circadian and aging processes have been implicated in the pathogenesis of NAFLD. We hypothesized that the prenatal BPA-induced fatty-liver phenotype of female sheep is associated with premature hepatic senescence and disruption in circadian clock genes. The expression of circadian rhythm and aging-associated genes, along with other markers of senescence such as telomere length, mitochondrial DNA copy number, and lipofuscin accumulation, were evaluated in the liver tissue of control and prenatal BPA groups. Prenatal BPA exposure significantly elevated the expression of aging-associated genes <i>GLB1</i> and <i>CISD2</i> and induced large magnitude differences in the expression of other aging genes—<i>APOE</i>, <i>HGF</i>, <i>KLOTHO,</i> and the clock genes <i>PER2</i> and <i>CLOCK</i>—in the liver; the other senescence markers remained unaffected. Prenatal BPA-programmed aging-related transcriptional changes in the liver may contribute to pathological changes in liver function, elucidating the involvement of aging genes in the pathogenesis of liver steatosis.https://www.mdpi.com/2305-6304/12/1/15DOHADcircadian genespremature senescenceovinelipofuscin |
| spellingShingle | Giuliana Motta Soundara Viveka Thangaraj Vasantha Padmanabhan Developmental Programming: Impact of Prenatal Exposure to Bisphenol A on Senescence and Circadian Mediators in the Liver of Sheep Toxics DOHAD circadian genes premature senescence ovine lipofuscin |
| title | Developmental Programming: Impact of Prenatal Exposure to Bisphenol A on Senescence and Circadian Mediators in the Liver of Sheep |
| title_full | Developmental Programming: Impact of Prenatal Exposure to Bisphenol A on Senescence and Circadian Mediators in the Liver of Sheep |
| title_fullStr | Developmental Programming: Impact of Prenatal Exposure to Bisphenol A on Senescence and Circadian Mediators in the Liver of Sheep |
| title_full_unstemmed | Developmental Programming: Impact of Prenatal Exposure to Bisphenol A on Senescence and Circadian Mediators in the Liver of Sheep |
| title_short | Developmental Programming: Impact of Prenatal Exposure to Bisphenol A on Senescence and Circadian Mediators in the Liver of Sheep |
| title_sort | developmental programming impact of prenatal exposure to bisphenol a on senescence and circadian mediators in the liver of sheep |
| topic | DOHAD circadian genes premature senescence ovine lipofuscin |
| url | https://www.mdpi.com/2305-6304/12/1/15 |
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