Chronic fetal hypoxia disrupts the peri-conceptual environment in next-generation adult female rats

Catherine Aiken, Jane L. Tarry-Adkins, Ana Mishel Spiroski, Anna M. Nuzzo, Thomas J. Ashmore, Alessandro Rolfo, Megan J. Sutherland, Emily J. Camm, Dino A. Giussani, Susan E. Ozanne

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2391-2401
Number of pages11
JournalJournal of Physiology
Volume597
Issue number9
DOIs
StatePublished - May 1 2019

Fingerprint

Fetal Hypoxia
Oviducts
Telomere
Mitochondrial DNA
Social Responsibility
Organelle Biogenesis
Hypoxia
Fertility
Health
Gene Expression
Reproductive Health
Adult Children
Fetal Development
Southern Blotting
Oxidants
Germ Cells

Keywords

  • Developmental programming
  • hypoxia
  • infertility
  • oviducts
  • reproductive ageing

ASJC Scopus subject areas

  • Physiology

Cite this

Aiken, C., Tarry-Adkins, J. L., Spiroski, A. M., Nuzzo, A. M., Ashmore, T. J., Rolfo, A., ... Ozanne, S. E. (2019). Chronic fetal hypoxia disrupts the peri-conceptual environment in next-generation adult female rats. Journal of Physiology, 597(9), 2391-2401. https://doi.org/10.1113/JP277431

Chronic fetal hypoxia disrupts the peri-conceptual environment in next-generation adult female rats. / Aiken, Catherine; 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.

In: Journal of Physiology, Vol. 597, No. 9, 01.05.2019, p. 2391-2401.

Research output: Contribution to journalArticle

Aiken, C, Tarry-Adkins, JL, Spiroski, AM, Nuzzo, AM, Ashmore, TJ, Rolfo, A, Sutherland, MJ, Camm, EJ, Giussani, DA & Ozanne, SE 2019, 'Chronic fetal hypoxia disrupts the peri-conceptual environment in next-generation adult female rats', Journal of Physiology, vol. 597, no. 9, pp. 2391-2401. https://doi.org/10.1113/JP277431
Aiken, Catherine ; 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. In: Journal of Physiology. 2019 ; Vol. 597, No. 9. pp. 2391-2401.
@article{3ca4c0ec0e3344e89fd8f3b242d7746a,
title = "Chronic fetal hypoxia disrupts the peri-conceptual environment in next-generation adult female rats",
abstract = "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.",
keywords = "Developmental programming, hypoxia, infertility, oviducts, reproductive ageing",
author = "Catherine Aiken and Tarry-Adkins, {Jane L.} and Spiroski, {Ana Mishel} and Nuzzo, {Anna M.} and Ashmore, {Thomas J.} and Alessandro Rolfo and Sutherland, {Megan J.} and Camm, {Emily J.} and Giussani, {Dino A.} and Ozanne, {Susan E.}",
year = "2019",
month = "5",
day = "1",
doi = "10.1113/JP277431",
language = "English (US)",
volume = "597",
pages = "2391--2401",
journal = "Journal of Physiology",
issn = "0022-3751",
publisher = "Wiley-Blackwell",
number = "9",

}

TY - JOUR

T1 - Chronic fetal hypoxia disrupts the peri-conceptual environment in next-generation adult female rats

AU - Aiken, Catherine

AU - Tarry-Adkins, Jane L.

AU - Spiroski, Ana Mishel

AU - Nuzzo, Anna M.

AU - Ashmore, Thomas J.

AU - Rolfo, Alessandro

AU - Sutherland, Megan J.

AU - Camm, Emily J.

AU - Giussani, Dino A.

AU - Ozanne, Susan E.

PY - 2019/5/1

Y1 - 2019/5/1

N2 - 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.

AB - 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.

KW - Developmental programming

KW - hypoxia

KW - infertility

KW - oviducts

KW - reproductive ageing

UR - http://www.scopus.com/inward/record.url?scp=85063284095&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85063284095&partnerID=8YFLogxK

U2 - 10.1113/JP277431

DO - 10.1113/JP277431

M3 - Article

VL - 597

SP - 2391

EP - 2401

JO - Journal of Physiology

JF - Journal of Physiology

SN - 0022-3751

IS - 9

ER -