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Gender differences in hypoxic acclimatization in cyclooxygenase-2-deficient mice
Kui Xu1, Xiaoyan Sun2, Girriso F Benderro2
1Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio kxx@case.edu.
Physiological Reports
|March 1, 2017
Summary
Cyclooxygenase-2 (COX-2) gene deletion impairs hypoxic acclimatization in male mice but not females. COX-2 is crucial for male adaptation to low oxygen environments, while females utilize alternative pathways.
Area of Science:
- Physiology
- Molecular Biology
- Genetics
Background:
- Hypobaric hypoxia triggers adaptive responses crucial for survival.
- Cyclooxygenase-2 (COX-2) plays a role in physiological adaptations.
- Gender-specific responses to hypoxia are not fully understood.
Purpose of the Study:
- To investigate the impact of COX-2 gene deletion on hypoxic acclimatization.
- To determine gender-specific differences in adaptive responses to hypobaric hypoxia.
Main Methods:
- Wild-type (WT) and COX-2 knockout (KO) mice of both genders were exposed to hypobaric hypoxia or normoxia for 21 days.
- Measurements included survival rates, hematocrit, brain capillary density, and levels of HIF-1α, Ang-2, and EPO.
Main Results:
- Male COX-2 KO mice showed reduced survival, erythropoiesis, and cerebral angiogenesis compared to WT and female KO mice.
- Hypoxia-induced upregulation of HIF-1α, VEGF, EPO, and Ang-2 was attenuated in male COX-2 KO mice.
- Female COX-2 KO mice exhibited adaptive responses similar to WT mice.
Conclusions:
- COX-2 signaling is essential for male hypoxic acclimatization but not for females.
- Female mice may utilize COX-2-independent pathways for adaptation to hypoxia.
- Physiologically significant gender differences exist in hypoxic acclimatization in COX-2-deficient mice.
