CD147 regulates apoptosis in mouse spermatocytes but not spermatogonia

Human Reproduction, Jun 2012

BACKGROUND Spermatogenesis is maintained by a dynamic balance between germ cell proliferation and apoptosis. Previous study has demonstrated that CD147 knockout mice are infertile with arrested germ cells. However, the question of whether and how CD147 may be involved in the apoptotic process during spermatogenesis remains elusive. The aim of this study was to evaluate the role of CD147 in the regulation of germ cell apoptosis in mice.

A PDF file should load here. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a PDF plug-in installed and enabled in your browser.

Alternatively, you can download the file locally and open with any standalone PDF reader:

https://humrep.oxfordjournals.org/content/27/6/1568.full.pdf

CD147 regulates apoptosis in mouse spermatocytes but not spermatogonia

Advanced Access publication on March CD147 regulates apoptosis in mouse spermatocytes but not spermatogonia Hao Chen 0 1 2 Kin Lam Fok 1 Xiaohua Jiang 1 4 Jianli Jiang 3 Zhinan Chen 3 Yaoting Gui 0 Hsiao Chang Chan 1 4 Zhiming Cai 0 2 0 Guangdong Key Laboratory of Male Reproduction and Genetics, Peking University Shenzhen Hospital, Shenzhen PKU- HKUST Medical Center , Shenzhen , PR China 1 Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong , Shatin , Hong Kong 2 Department of Gynaecology, The Second People's Hospital of Shenzhen, The First Affiliated Hospital of Shenzhen University , Shenzhen , PR China 3 Cell Engineering Research Centre and Department of Cell Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University , Xi'an, Shanxi , PR China 4 Key Laboratory for Regenerative Medicine (Jinan University - The Chinese University of Hong Kong), Ministry of Education of the People's Republic of China , PR China background: Spermatogenesis is maintained by a dynamic balance between germ cell proliferation and apoptosis. Previous study has demonstrated that CD147 knockout mice are infertile with arrested germ cells. However, the question of whether and how CD147 may be involved in the apoptotic process during spermatogenesis remains elusive. The aim of this study was to evaluate the role of CD147 in the regulation of germ cell apoptosis in mice. methods: CD147 function was blocked by anti-CD147 antibody in GC-1 (immortalized spermatogonia) and GC-2 (immortalized spermatocytes) cell lines and in testicular germ cells in vivo. Testes size and weight were examined after injection of anti-CD147 antibody into the seminiferous tubules of severe combined immunodeficiency mice. Germ cell apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and levels of p53 and two effectors, caspase 3 and poly ADP-ribose polymerase (PARP), using western blots. results: The size and weight of the CD147-immunodepleted testes were decreased compared with that in control testes (P , 0.001). The TUNEL assay showed an increase in the number of apoptotic spermatocytes (P , 0.001 versus control) but not spermatogonia in Stages XI - XII of CD147-immunodepleted testes. In addition, in vitro experiments demonstrated that CD147 immunodepletion induced an increase in apoptosis in GC-2 cells (P , 0.001 versus control) but had no effect on GC-1 cells. Moreover, deprivation of CD147 induced apoptosis in spermatocytes through a p53-independent mechanism, which led to caspase 3 and PARP activation. conclusions: We have demonstrated that immunodepletion of CD147 induces p53-independent apoptosis in mouse spermatocytes but not spermatogonia. CD147 / apoptosis / spermatogenesis / spermatocyte / spermatogonia Introduction Spermatogenesis is a unique process that involves a series of cellular and biochemical events, stepping from mitosis of spermatogonia, meiosis of spermatocyte, to spermiogenesis (de Kretser et al., 1998) . Thus, the process must be under precise regulation to attain a homeostatic state that ensures the quality and quantity of mature spermatozoa. This fine-tuned homeostasis is, however, achieved at a substantially high cost in which up to 75% of germ cells from various stages undergo apoptosis in the testis (Huckins, 1978; Allan † These authors contributed equally to this work. et al., 1987) . Accordingly, a complex combination of integrated signals constitutes an intricate network of pathways directing the cells to survive or die. In fact, de-regulation of germ cell apoptosis, leading to neoplasia (Spierings et al., 2003) or azoospermia (Sciurano et al., 2006; Bozec et al., 2008) , has been demonstrated in humans, highlighting the importance of tight control of programmed cell death in spermatogenesis (Blanco-Rodr´ıguez et al., 1998). Germ cell apoptosis in the testis is regulated by both extrinsic and intrinsic pathways. Although caspase-independent apoptosis has been reported (Coureuil et al., 2006) , the majority of apoptotic stimuli from both extrinsic and intrinsic pathways in germ cells are executed by activation of the caspase family (Kawamura et al., 2004; Said et al., 2004; Theas et al., 2006; Yin et al., 2007; Sofikitis et al., 2008; Aitken et al., 2011) . It has been demonstrated that p53 acts as a key player in the cellular response to multiple stresses and promotes apoptosis in both extrinsic and intrinsic pathways during spermatogenesis (Fridman and Lowe, 2003). Three transmembrane proteins [Fas/CD95, DR5 and poly ADP-ribose polymerase (PARP)] serve as the targets of p53-mediated extrinsic apoptotic cell death and have been implicated in responses to g-irradiation and other stimuli (Wu et al., 1997; Bouvard et al., 2000; Burns et al., 2001) . On the other hand, a p53-mediated intrinsic apoptotic pathway has been demonstrated to activate a pro-apoptotic sub (...truncated)


This is a preview of a remote PDF: https://humrep.oxfordjournals.org/content/27/6/1568.full.pdf

Hao Chen, Kin Lam Fok, Xiaohua Jiang, Jianli Jiang, Zhinan Chen, Yaoting Gui, Hsiao Chang Chan, Zhiming Cai. CD147 regulates apoptosis in mouse spermatocytes but not spermatogonia, Human Reproduction, 2012, pp. 1568-1576, 27/6, DOI: 10.1093/humrep/des050