Expression of retinoic acid signaling pathway in uterus injury induced by procymidone in adolescent mice

Abstract

To investigate the expression of key genes and proteins of retinoic acid signaling pathway in procymidone-induced uterine injury in adolescent mice, and analyze the relationship between the signaling pathway and female reproductive damage. The 3-week age ICR mice were randomly divided into low, medium, and high-dose groups and one control group with 8 mice in each group by weight. The low, medium and high dose groups were respectively given 50, 100 and 200 mg/(kg·d) procymidone orally for 21 days continuously, while the control group was given equal volume of soybean oil. After the mice were sacrificed, the uterus was taken from both sides for observing the histological changes in the cross-sectional slices of the uterus, the detection of the expression abundance of genes which related to the retinoic acid signaling pathway by the real-time fluorescent quantitative PCR, and the measurement of ALDH2 and CYP26 a1 proteins expression by Western blot. The body weight of mice in low-dose, medium-dose and high-dose groups were(27.50±1.49) g, (27.72±1.40) g and(26.89±1.19) g, respectively, which were lower than those in control group(31.48±1.14) g(P<0.05). The density of uterine lining monolayer columnar epithelium and lamina propria tubular uterine glands gradually decreases, at the same time the uterine folds become less with the dose of procymidone increases. adh1, ad/2, aldh1a1 in each experimental group were higher than those in the control group(P<0.05); the expression levels of aldh1a2 and aldh1a3 genes in the middle and high dose groups were higher than those in the control group(P<0.05); the expression levels of retinoic acid nuclear receptor rarα, rarγ, rxrα and rxrβ genes in the high-dose group were higher than those in the control(P<0.05); yet the expression levels of cyp26a2 and cyp26a3 in the high-dose group were lower than those in the control group(P<0.05); the jnk family in medium and high dose groups were higher than the control(P<0.05). The expression of ALDH2 in each experimental group was higher than that in the control group, and increased with the increase of the dose(P<0.05); the expression of CYP26 a1 in each experimental group was not significantly different from that of the control group. The retinoic acid signal pathway is activated in procymidone-induced uterine injury in mice, then regulates the increase of the expression of jnk family, leading to the damage.