Expression of retinoic acid signaling pathway in mouse damaged testes induced by procymidone during adolescence

Bingyan Xin; Rui LI; Qing Wang; Erjin Zuo; Hu FU; Zhengli Yan; Yongfei Zhu

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Expression of retinoic acid signaling pathway in mouse damaged testes induced by procymidone during adolescence

VernacularTitle:视黄酸信号通路在腐霉利致青春期小鼠睾丸损伤中的表达特征
Author: Bingyan XIN ¹ ; Rui LI ¹ ; Qing WANG ¹ ; Erjin ZUO ¹ ; Hu FU ¹ ; Zhengli YAN ¹ ; Yongfei ZHU ¹
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1. Department of Preventive Medicine, Medical School, Hunan Normal University, Changsha, Hunan 410013, China.
Publication Type:Experiment
Keywords: procymidone; adolescence; testis; retinoic acid signaling pathway; testosterone
From: Journal of Environmental and Occupational Medicine 2022;39(2):186-192
CountryChina
Language:Chinese
Abstract: Background Procymidone (PCM) exposure can cause damage to reproductive organs of male mice, but whether its mechanism is related to the retinoic acid (RA) signaling pathway is unclear. Objective To explore the possible mechanism of PCM-induced testes damage in adolescent mice. Methods Three-week-old ICR mice (n=64) were randomly divided into a control group and three dose groups (low, medium, and high), with 16 mice in each group. PCM was administered orally at 0, 50, 100, and 200 mg·kg⁻¹·d⁻¹ for 21 consecutive days. Serum and bilateral testes in each mouse were collected to detect content of testosterone in serum and to observe histological changes in testis section after the mice were sacrificed one week after cessation of drug administration. Real-time fluorescence quantitative PCR and Western blotting were used to detect the mRNA expression abundances of genes related to the RA signaling pathway and apoptosis genes Casp9 and Casp12, and the protein expression levels of CYP26A1, ALDH2, and CASP9 respectively. Results Compared with the control group, there was no significant change in the overall appearance and testicular appearance of mice in each dose group after the PCM exposure. According to pathological section observation, the testicular seminiferous tubules of mice in the low-dose group showed slight atrophy and reduced sperm production; the testes of mice in the medium- and the high-dose groups showed obvious pathological damage (e.g. dilated lumen of seminiferous tubules, damaged spermatogenic epithelium, decreased number of spermatogonia, and partial absence of sertoli cells); as the concentration of PCM increased, the degree of spermatogenic epithelial damage in mice gradually increased and the number of spermatozoa in the seminiferous tubules decreased. There were no significant differences in the distance between the anus and the genitals, testicular mass, testicular volume, and testicular organ coefficient among the four groups of mice (P>0.05). The body weights of the mice in the low-, medium-, and high-dose groups were (34.91±1.89), (34.88±1.75), and (32.94±1.37) g respectively, and that in the high-dose group was lower than that in the control group, (35.93±1.99) g, (P<0.05); the serum testosterone concentrations were (313.77±5.32), (305.31±3.47), and (304.80±5.28) pg·mL⁻¹ respectively, which were lower than that in the control group, (319.05±1.92) pg·mL⁻¹ (P<0.05); as the dose of PCM increased, the body weight and serum testosterone concentration showed decreasing trends. The mRNA expression levels of Stra6 and Rbp1 in the high-dose group were higher than those in the control group (P<0.05); the mRNA expression levels of Aldh2, Aldh1a1, Aldh1a3, Rarα, Rar\begin{document}$\beta $\end{document}, Rxrα and Rxr\begin{document}$\beta $\end{document} in the medium-and the high-dose groups were higher than those in the control group (P<0.05); the mRNA expression levels of Cyp26a1 and Cyp26b1 in the medium- and high-dose groups were lower than those in the control group(P<0.05); the mRNA expression levels of apoptosis genes Casp9 and Casp12 in the medium-and the high-dose groups were higher than those in the control group (P<0.05). The protein expression level of CYP26A1 in each exposure group was lower than that in the control group (P<0.05), and the expression level decreased with increasing concentration of PCM; the expression level of ALDH2 protein in the medium- and the high-dose groups and the protein expression level of CASP9 in each exposure group were higher than those in the control group (P<0.05), and the levels increased with increasing concentration of PCM. Conclusion PCM can damage the testis tissues of adolescent mice, where RA signaling pathway, Casp9 and Casp12 genes, and CASP9 protein are activated.