Developmental Exposure to DDT Disrupts Transcriptional Regulation of Postnatal Growth and Cell Renewal of Adrenal Medulla
Dichlorodiphenyltrichloroethane (DDT) is the most widespread persistent pollutant with endocrine-disrupting properties. DDT has been shown to disrupt secretory and morphogenetic processes in the adrenal cortex. The present investigation aimed to evaluate transcriptional regulation of postnatal growt...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-02-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/3/2774 |
| _version_ | 1797624220288548864 |
|---|---|
| author | Nataliya V. Yaglova Svetlana V. Nazimova Sergey S. Obernikhin Dibakhan A. Tsomartova Valentin V. Yaglov Ekaterina P. Timokhina Elina S. Tsomartova Elizaveta V. Chereshneva Marina Y. Ivanova Tatiana A. Lomanovskaya |
| author_facet | Nataliya V. Yaglova Svetlana V. Nazimova Sergey S. Obernikhin Dibakhan A. Tsomartova Valentin V. Yaglov Ekaterina P. Timokhina Elina S. Tsomartova Elizaveta V. Chereshneva Marina Y. Ivanova Tatiana A. Lomanovskaya |
| author_sort | Nataliya V. Yaglova |
| collection | DOAJ |
| description | Dichlorodiphenyltrichloroethane (DDT) is the most widespread persistent pollutant with endocrine-disrupting properties. DDT has been shown to disrupt secretory and morphogenetic processes in the adrenal cortex. The present investigation aimed to evaluate transcriptional regulation of postnatal growth of the adrenal medulla and formation of the pools necessary for self-renewal of medullary cells in rats that developed under low-dose exposure to DDT. The study was performed using male Wistar rats exposed to low doses of o,p’-DDT during prenatal and postnatal development. Light microscopy and histomorphometry revealed diminished medulla growth in the DDT-exposed rats. Evaluation of Ki-67 expression in chromaffin cells found later activation of proliferation indicative of retarded growth of the adrenal medulla. All DDT-exposed rats exhibited a gradual decrease in tyrosine hydroxylase production by adrenal chromaffin cells. Immunohistochemical evaluation of nuclear β-catenin, transcription factor Oct4, and ligand of sonic hedgehog revealed increased expression of all factors after termination of growth in the control rats. The DDT-exposed rats demonstrated diminished increases in Oct4 and sonic hedgehog expression and lower levels of canonical Wnt signaling activation. Thus, developmental exposure to the endocrine disruptor o,p’-DDT alters the transcriptional regulation of morphogenetic processes in the adrenal medulla and evokes a slowdown in its growth and in the formation of a reserve pool of cells capable of dedifferentiation and proliferation that maintain cellular homeostasis in adult adrenals. |
| first_indexed | 2024-03-11T09:39:52Z |
| format | Article |
| id | doaj.art-5f82c1de0db24c049c5e1c6dff1800d1 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T09:39:52Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5f82c1de0db24c049c5e1c6dff1800d12023-11-16T17:02:12ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01243277410.3390/ijms24032774Developmental Exposure to DDT Disrupts Transcriptional Regulation of Postnatal Growth and Cell Renewal of Adrenal MedullaNataliya V. Yaglova0Svetlana V. Nazimova1Sergey S. Obernikhin2Dibakhan A. Tsomartova3Valentin V. Yaglov4Ekaterina P. Timokhina5Elina S. Tsomartova6Elizaveta V. Chereshneva7Marina Y. Ivanova8Tatiana A. Lomanovskaya9Laboratory of Endocrine System Development, A.P. Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution “Petrovsky National Research Center of Surgery”, 119991 Moscow, RussiaLaboratory of Endocrine System Development, A.P. Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution “Petrovsky National Research Center of Surgery”, 119991 Moscow, RussiaLaboratory of Endocrine System Development, A.P. Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution “Petrovsky National Research Center of Surgery”, 119991 Moscow, RussiaLaboratory of Endocrine System Development, A.P. Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution “Petrovsky National Research Center of Surgery”, 119991 Moscow, RussiaLaboratory of Endocrine System Development, A.P. Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution “Petrovsky National Research Center of Surgery”, 119991 Moscow, RussiaLaboratory of Endocrine System Development, A.P. Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution “Petrovsky National Research Center of Surgery”, 119991 Moscow, RussiaLaboratory of Endocrine System Development, A.P. Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution “Petrovsky National Research Center of Surgery”, 119991 Moscow, RussiaDepartment of Human Anatomy and Histology, Federal State Funded Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University, 119435 Moscow, RussiaDepartment of Human Anatomy and Histology, Federal State Funded Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University, 119435 Moscow, RussiaDepartment of Human Anatomy and Histology, Federal State Funded Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University, 119435 Moscow, RussiaDichlorodiphenyltrichloroethane (DDT) is the most widespread persistent pollutant with endocrine-disrupting properties. DDT has been shown to disrupt secretory and morphogenetic processes in the adrenal cortex. The present investigation aimed to evaluate transcriptional regulation of postnatal growth of the adrenal medulla and formation of the pools necessary for self-renewal of medullary cells in rats that developed under low-dose exposure to DDT. The study was performed using male Wistar rats exposed to low doses of o,p’-DDT during prenatal and postnatal development. Light microscopy and histomorphometry revealed diminished medulla growth in the DDT-exposed rats. Evaluation of Ki-67 expression in chromaffin cells found later activation of proliferation indicative of retarded growth of the adrenal medulla. All DDT-exposed rats exhibited a gradual decrease in tyrosine hydroxylase production by adrenal chromaffin cells. Immunohistochemical evaluation of nuclear β-catenin, transcription factor Oct4, and ligand of sonic hedgehog revealed increased expression of all factors after termination of growth in the control rats. The DDT-exposed rats demonstrated diminished increases in Oct4 and sonic hedgehog expression and lower levels of canonical Wnt signaling activation. Thus, developmental exposure to the endocrine disruptor o,p’-DDT alters the transcriptional regulation of morphogenetic processes in the adrenal medulla and evokes a slowdown in its growth and in the formation of a reserve pool of cells capable of dedifferentiation and proliferation that maintain cellular homeostasis in adult adrenals.https://www.mdpi.com/1422-0067/24/3/2774adrenal medullaDDTendocrine-disrupting chemicalsgrowthself-renewalOct4 |
| spellingShingle | Nataliya V. Yaglova Svetlana V. Nazimova Sergey S. Obernikhin Dibakhan A. Tsomartova Valentin V. Yaglov Ekaterina P. Timokhina Elina S. Tsomartova Elizaveta V. Chereshneva Marina Y. Ivanova Tatiana A. Lomanovskaya Developmental Exposure to DDT Disrupts Transcriptional Regulation of Postnatal Growth and Cell Renewal of Adrenal Medulla International Journal of Molecular Sciences adrenal medulla DDT endocrine-disrupting chemicals growth self-renewal Oct4 |
| title | Developmental Exposure to DDT Disrupts Transcriptional Regulation of Postnatal Growth and Cell Renewal of Adrenal Medulla |
| title_full | Developmental Exposure to DDT Disrupts Transcriptional Regulation of Postnatal Growth and Cell Renewal of Adrenal Medulla |
| title_fullStr | Developmental Exposure to DDT Disrupts Transcriptional Regulation of Postnatal Growth and Cell Renewal of Adrenal Medulla |
| title_full_unstemmed | Developmental Exposure to DDT Disrupts Transcriptional Regulation of Postnatal Growth and Cell Renewal of Adrenal Medulla |
| title_short | Developmental Exposure to DDT Disrupts Transcriptional Regulation of Postnatal Growth and Cell Renewal of Adrenal Medulla |
| title_sort | developmental exposure to ddt disrupts transcriptional regulation of postnatal growth and cell renewal of adrenal medulla |
| topic | adrenal medulla DDT endocrine-disrupting chemicals growth self-renewal Oct4 |
| url | https://www.mdpi.com/1422-0067/24/3/2774 |
| work_keys_str_mv | AT nataliyavyaglova developmentalexposuretoddtdisruptstranscriptionalregulationofpostnatalgrowthandcellrenewalofadrenalmedulla AT svetlanavnazimova developmentalexposuretoddtdisruptstranscriptionalregulationofpostnatalgrowthandcellrenewalofadrenalmedulla AT sergeysobernikhin developmentalexposuretoddtdisruptstranscriptionalregulationofpostnatalgrowthandcellrenewalofadrenalmedulla AT dibakhanatsomartova developmentalexposuretoddtdisruptstranscriptionalregulationofpostnatalgrowthandcellrenewalofadrenalmedulla AT valentinvyaglov developmentalexposuretoddtdisruptstranscriptionalregulationofpostnatalgrowthandcellrenewalofadrenalmedulla AT ekaterinaptimokhina developmentalexposuretoddtdisruptstranscriptionalregulationofpostnatalgrowthandcellrenewalofadrenalmedulla AT elinastsomartova developmentalexposuretoddtdisruptstranscriptionalregulationofpostnatalgrowthandcellrenewalofadrenalmedulla AT elizavetavchereshneva developmentalexposuretoddtdisruptstranscriptionalregulationofpostnatalgrowthandcellrenewalofadrenalmedulla AT marinayivanova developmentalexposuretoddtdisruptstranscriptionalregulationofpostnatalgrowthandcellrenewalofadrenalmedulla AT tatianaalomanovskaya developmentalexposuretoddtdisruptstranscriptionalregulationofpostnatalgrowthandcellrenewalofadrenalmedulla |