Objective Explore the expression characteristics of RA signaling pathway in ovarian injury in adolescent mice. Methods Sixty-four 4-week-old female ICR mice were randomly assigned to low-dose, medium-dose, high-dose exposure groups and a control group, with 16 mice in each group. The exposure groups were orally administered 50, 100, and 200 mg·(kg·d)-1 of procymidone continuously for 21 days, while the control group received an equal volume of soybean oil. Seven days after the last administration, the mice were euthanized, and serum and bilateral ovarian tissues were collected. The concentration of estradiol in serum was determined by enzyme-linked immunosorbent assay. Histopathological techniques were used to analyze changes in ovarian microstructure. Quantitative Real-time polymerase chain reaction and Western blotting were employed to measure the levels of genes and proteins related to the retinoic acid signaling pathway and apoptosis in ovarian tissues, respectively. Results Compared with the control group, there were no significant changes in food and water intake in mice of each procymidone group. With the increase in procymidone dose, the number of follicles at all stages in the mouse ovaries gradually decreased. At weeks 5, 6, and 7, the body weights of mice in all dose groups were lower than those in the control group. The ovarian weights of all dose groups were lower than those of the control group, and the ovarian organ coefficients of the medium- and high-dose groups (0.55±0.09 and 0.52±0.08, respectively) were lower than those of the control group (0.64±0.11). The serum E2 concentrations in the low-, medium-, and high-dose groups were 65.15±7.01, 52.69±7.78, and 56.54±6.93 pg/mL, respectively, all of which were lower than that in the control group (72.10±6.31 pg/mL). The abundances of Adh1, Aldh1a1, Aldh1a2, Aldh1a3, Rarα, and Rarβ in the medium- and high-dose groups were higher than those in the control group, while Cyp26b1 was decreased. Meanwhile, the apoptotic genes Jnk1, Jnk2, and Jnk3 were upregulated in the medium- and high-dose groups. The protein expression levels of ADH1 and ALDH2 in the medium- and high-dose groups were higher than those in the control group and increased with the dose. The protein expression level of CYP26A1 in the high-dose group was lower than that in the control group. Conclusion Exposure to procymidone activated the retinoic acid signaling pathway and upregulated the expression of JNK family genes in adolescent female mice, ultimately leading to ovarian injury.
Key words
procymidone /
ovary /
injury /
retinoic acid pathway
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