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Chronic fetal hypoxia disrupts the peri‐conceptual environment in next‐generation adult female rats
KEY POINTS: Exposure to chronic hypoxia during gestation influences long‐term health and development, including reproductive capacity, across generations. If the peri‐conceptual environment in the developing oviduct is affected by gestational hypoxia, then this could have implications for later fert...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6487938/ https://www.ncbi.nlm.nih.gov/pubmed/30791124 http://dx.doi.org/10.1113/JP277431 |
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author | Aiken, Catherine E. Tarry‐Adkins, Jane L. Spiroski, Ana‐Mishel Nuzzo, Anna M. Ashmore, Thomas J. Rolfo, Alessandro Sutherland, Megan J. Camm, Emily J. Giussani, Dino A. Ozanne, Susan E. |
author_facet | Aiken, Catherine E. Tarry‐Adkins, Jane L. Spiroski, Ana‐Mishel Nuzzo, Anna M. Ashmore, Thomas J. Rolfo, Alessandro Sutherland, Megan J. Camm, Emily J. Giussani, Dino A. Ozanne, Susan E. |
author_sort | Aiken, Catherine E. |
collection | PubMed |
description | KEY POINTS: Exposure to chronic hypoxia during gestation influences long‐term health and development, including reproductive capacity, across generations. If the peri‐conceptual environment in the developing oviduct is affected by gestational hypoxia, then this could have implications for later fertility and the health of future generations. In the present study, we show that the oviducts of female rats exposed to chronic hypoxia in utero have reduced telomere length, decreased mitochondrial DNA biogenesis and increased oxidative stress. The results of the present study show that exposure to chronic gestational hypoxia leads to accelerated ageing of the oviduct in early adulthood and they help us understand how exposure to hypoxia during development could influence reproductive health across generations. ABSTRACT: Exposure to chronic hypoxia during fetal development has important effects on immediate and long‐term outcomes in offspring. Adverse impacts in adult offspring include impairment of cardiovascular function, metabolic derangement and accelerated ovarian ageing. However, it is not known whether other aspects of the female reproductive system may be similarly affected. In the present study, we examined the impact of chronic gestational hypoxia on the developing oviduct. Wistar rat dams were randomized to either normoxia (21%) or hypoxia (13%) from day 6 post‐mating until delivery. Post‐delivery female offspring were maintained in normoxia until 4 months of age. Oviductal gene expression was assayed at the RNA (quantitative RT‐PCR) and protein (western blotting) levels. Oviductal telomere length was assayed using Southern blotting. Oviductal telomere length was reduced in the gestational hypoxia‐exposed animals compared to normoxic controls (P < 0.01). This was associated with a specific post‐transcriptional reduction in the KU70 subunit of DNA‐pk in the gestational hypoxia‐exposed group (P < 0.05). Gestational hypoxia‐exposed oviducts also showed evidence of decreased mitochondrial DNA biogenesis, reduced mtDNA copy number (P < 0.05) and reduced gene expression of Tfam (P < 0.05) and Pgc1α (P < 0.05). In the hypoxia‐exposed oviducts, there was upregulation of mitochondrial‐specific anti‐oxidant defence enzymes (MnSOD; P < 0.01). Exposure to chronic gestational hypoxia leads to accelerated ageing of the oviduct in adulthood. The oviduct plays a central role in early development as the site of gamete transport, syngamy, and early development; hence, accelerated ageing of the oviductal environment could have important implications for fertility and the health of future generations. |
format | Online Article Text |
id | pubmed-6487938 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-64879382019-05-06 Chronic fetal hypoxia disrupts the peri‐conceptual environment in next‐generation adult female rats Aiken, Catherine E. Tarry‐Adkins, Jane L. Spiroski, Ana‐Mishel Nuzzo, Anna M. Ashmore, Thomas J. Rolfo, Alessandro Sutherland, Megan J. Camm, Emily J. Giussani, Dino A. Ozanne, Susan E. J Physiol Placenta, Pregnancy and Perinatal Physiology KEY POINTS: Exposure to chronic hypoxia during gestation influences long‐term health and development, including reproductive capacity, across generations. If the peri‐conceptual environment in the developing oviduct is affected by gestational hypoxia, then this could have implications for later fertility and the health of future generations. In the present study, we show that the oviducts of female rats exposed to chronic hypoxia in utero have reduced telomere length, decreased mitochondrial DNA biogenesis and increased oxidative stress. The results of the present study show that exposure to chronic gestational hypoxia leads to accelerated ageing of the oviduct in early adulthood and they help us understand how exposure to hypoxia during development could influence reproductive health across generations. ABSTRACT: Exposure to chronic hypoxia during fetal development has important effects on immediate and long‐term outcomes in offspring. Adverse impacts in adult offspring include impairment of cardiovascular function, metabolic derangement and accelerated ovarian ageing. However, it is not known whether other aspects of the female reproductive system may be similarly affected. In the present study, we examined the impact of chronic gestational hypoxia on the developing oviduct. Wistar rat dams were randomized to either normoxia (21%) or hypoxia (13%) from day 6 post‐mating until delivery. Post‐delivery female offspring were maintained in normoxia until 4 months of age. Oviductal gene expression was assayed at the RNA (quantitative RT‐PCR) and protein (western blotting) levels. Oviductal telomere length was assayed using Southern blotting. Oviductal telomere length was reduced in the gestational hypoxia‐exposed animals compared to normoxic controls (P < 0.01). This was associated with a specific post‐transcriptional reduction in the KU70 subunit of DNA‐pk in the gestational hypoxia‐exposed group (P < 0.05). Gestational hypoxia‐exposed oviducts also showed evidence of decreased mitochondrial DNA biogenesis, reduced mtDNA copy number (P < 0.05) and reduced gene expression of Tfam (P < 0.05) and Pgc1α (P < 0.05). In the hypoxia‐exposed oviducts, there was upregulation of mitochondrial‐specific anti‐oxidant defence enzymes (MnSOD; P < 0.01). Exposure to chronic gestational hypoxia leads to accelerated ageing of the oviduct in adulthood. The oviduct plays a central role in early development as the site of gamete transport, syngamy, and early development; hence, accelerated ageing of the oviductal environment could have important implications for fertility and the health of future generations. John Wiley and Sons Inc. 2019-03-24 2019-05-01 /pmc/articles/PMC6487938/ /pubmed/30791124 http://dx.doi.org/10.1113/JP277431 Text en © 2019 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Placenta, Pregnancy and Perinatal Physiology Aiken, Catherine E. Tarry‐Adkins, Jane L. Spiroski, Ana‐Mishel Nuzzo, Anna M. Ashmore, Thomas J. Rolfo, Alessandro Sutherland, Megan J. Camm, Emily J. Giussani, Dino A. Ozanne, Susan E. Chronic fetal hypoxia disrupts the peri‐conceptual environment in next‐generation adult female rats |
title | Chronic fetal hypoxia disrupts the peri‐conceptual environment in next‐generation adult female rats |
title_full | Chronic fetal hypoxia disrupts the peri‐conceptual environment in next‐generation adult female rats |
title_fullStr | Chronic fetal hypoxia disrupts the peri‐conceptual environment in next‐generation adult female rats |
title_full_unstemmed | Chronic fetal hypoxia disrupts the peri‐conceptual environment in next‐generation adult female rats |
title_short | Chronic fetal hypoxia disrupts the peri‐conceptual environment in next‐generation adult female rats |
title_sort | chronic fetal hypoxia disrupts the peri‐conceptual environment in next‐generation adult female rats |
topic | Placenta, Pregnancy and Perinatal Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6487938/ https://www.ncbi.nlm.nih.gov/pubmed/30791124 http://dx.doi.org/10.1113/JP277431 |
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