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Diagnostic Ultrasound Imaging of Mouse Diaphragm Function
Published on: April 21, 2014
Intrauterine growth restriction affects diaphragm function in adult female and male mice
Maddison R Francis1, Gavin J Pinniger1, Peter B Noble1
1School of Human Sciences, The University of Western Australia, Crawley, Western Australia, Australia.
Insights
Intrauterine growth restriction (IUGR) impacts adult mouse diaphragm function, causing slower relaxation but no structural changes. Sex also independently influences diaphragm contraction, highlighting long-term effects on respiratory health.
Area of Science:
- Physiology
- Developmental Biology
- Respiratory Medicine
Background:
- Diaphragm development in utero is crucial for postnatal respiratory function.
- Disturbances during fetal development can lead to diaphragm dysfunction and respiratory issues.
- Intrauterine growth restriction (IUGR) affects respiratory function in a sex-dependent manner, but its impact on the diaphragm is unknown.
Purpose of the Study:
- To investigate the impact of IUGR on diaphragm function and structure in adult male and female offspring.
- To utilize a maternal hypoxia-induced mouse model of IUGR.
Main Methods:
- Maternal hypoxia exposure from gestational days 11-17.5 in BALB/c mice.
- Offspring diaphragms assessed at 8 weeks for function (organ bath) and histology.
- Comparison between IUGR and control groups, and between male and female offspring.
Main Results:
- IUGR offspring were lighter at birth and at 8 weeks.
- Diaphragm force was unaffected, but IUGR led to longer half-relaxation time.
- Females showed lower maximum force development and higher fatigue resistance than males, irrespective of IUGR.
- No differences in myofibre cross-sectional area were observed.
Conclusions:
- Sex and IUGR independently affect diaphragm contractile function in adult mice without structural alterations.
- IUGR impacts later-life diaphragm contractile function.
- This dysfunction could impair respiratory function under increased load.
Background:
In utero diaphragm development is critically important for postnatal respiratory function and any disturbance to fetal development may lead to diaphragm dysfunction and respiratory complications in the postnatal period. Intrauterine growth restriction (IUGR) has been shown to affect respiratory function in a sex-dependent manner; however, the effect of IUGR on diaphragm function is unknown.
Aim:
This study used a maternal hypoxia-induced mouse model of IUGR to investigate the impact of IUGR on diaphragm function and structure in male and female adult offspring.
Materials And Methods:
Pregnant BALB/c mice were housed under hypoxic conditions (10.5% O2 ) from gestational days 11 to 17.5 and then returned to normoxic conditions. Control mice were housed under normoxic conditions throughout pregnancy. At 8 weeks of age, offspring were euthanized and diaphragms isolated for functional assessment in organ bath experiments and for histological analysis.
Results:
IUGR offspring were lighter at birth and remained lighter at 8 weeks of age compared to Controls. While diaphragm force (maximal or twitch) was not affected by treatment or sex, the IUGR group exhibited a longer half-relaxation time after twitch contractions compared to Control. Female offspring had a lower maximum rate of force development and higher fatigue resistance compared to males, independent of IUGR. There was no difference in the diaphragm myofibre cross-sectional area between groups or sexes.
Conclusion:
Sex and IUGR independently affect diaphragm contraction in adult mice without changes in structure. This study demonstrates that IUGR affects diaphragm contractile function in later life and could impair respiratory function if exacerbated under conditions of increased respiratory load.

