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The Testicular Pathology of Male Infertility in Niemann-Pick Disease Type C1 Mice

Song Ying^1,2, Yang Jichao^2,3, Li Xiaoying^1,2, Li Xixi^1,2, Tao Ziying^2,4, Ma Mengxue^1,2, Wang Shuai^1,2, Qiao Liang^1,2*, Lin Juntang^1,2,5*

(¹School of Life Science and Technology, Xinxiang Medical University, Xinxiang 453003, China;²Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang 453003, China;³Institute of mental and neurology, Xinxiang Medical University, Xinxiang 453003, China; ⁴The third clinical college, Xinxiang Medical University, Xinxiang 453003, China;⁵College of Biomedical Engineering, Xinxiang Medical University, Xinxiang 453003, China)

Abstract:

In this paper, we mainly studied the testicular pathological changes of male infertility in Niemann-Pick disease type C1 mice (Npc1–/–mice), and further explored the effect of Npc1 gene on male infertility. Twelve P60 Npc1–/– and Npc1+/+ male mice were randomly selected to observe the incidence of cryptorchidism. The testicular tissues were collected from P20, P40 and P60 Npc1–/– and Npc1+/+ male mice to calculate testicular weight and testicular index. HE staining was performed to observe the layers of germ cells and measure the diameter of seminiferous tubules. PAS staining was used to observe the cycle of germ cells and count relative percentage of spermatocyte in the total number of cells. Oil red O staining was performed to observe the lipid storage of leydig cells. Finally, testicular tissues of P60 Npc1–/– and Npc1+/+ male mice were randomly selected to observe the apoptosis of germ cells by TUNEL staining, and the expression levels of apoptotic proteins Cleaved-caspase-3, Cleaved-caspase-9, p53, Bax and Bcl-2 were detected by Western blot. The results showed, compared with Npc1+/+ male mice, cryptorchidism occurred in all Npc1–/– mice, testicular weight and index were decreased significantly (P<0.05, P<0.001), germ cell layers were not obvious, diameter of seminiferous tubules were also decreased significantly (P<0.001), spermatogenic cycle was irregular and the spermatogonial cells number were decreased significantly (P<0.001), and lipid storage in leydig cells were also decreased significantly (P<0.001). Apoptosis increased significantly (P<0.001), and the expression of Cleaved-caspase-3, Cleaved-caspase-9, p53 and Bax increased significantly (P<0.001) and the ratio of Bax/Bcl-2 increased significantly (P<0.001). The mutation of Npc1 gene leads to cryptorchidism, the decrease of lipid storage in leydig cells, and the apoptosis of germ cells. Therefore, Npc1 gene may become the new targets for male infertility.

CSTR: 32200.14.cjcb.2019.07.0006