Hypoxic preconditioning ameliorates endometrial and myometrial damage and improves uterine function following prolonged hypoxia in nonpregnant rats

Normal repeated uterine contractions are associated with uterine hypoxic stresses, and uterine transplantation and severe bleeding during hysterectomy may lead to hypoxia and irreversible cellular damage. This study investigated the effects of short repeated hypoxic episodes on the structure and function of uterine tissues following sustained prolonged hypoxia. Small segments of uterine tissue were dissected from three groups of nonpregnant rats and mounted in a tissue bath system. Prolonged hypoxia markedly increased the infiltration of eosinophils into the myometrium and caused fibrotic stroma and degeneration of endometrial glands with marked infiltration of eosinophils into the endometrium compared to the control group. In addition, the mean myometrial contractile function significantly decreased to 69 +/- 1% compared to 100% control with irregular and uncoordinated contractile activity (p < 0.01). Intriguingly, preconditioning with brief hypoxic episodes prevented the endometrial and myometrial degenerative changes. Although the mean myometrial contractile function decreased to 80 +/- 3% during reoxygenation compared to the 100% control, the entire force was greater than the force in the non-preconditioned group (p < 0.01). These results provide compelling evidence that prolonged hypoxia exacerbates the degree of cellular damage and that preconditioning with repeated cycles of short hypoxia/reoxygenation can ameliorate cellular damage.