INSERM U 1065, C3M, 151 route Saint-Antoine de Ginestière, BP 2 3194, 06204 Nice cedex 3, France.
Curr Mol Med. 2013 Sep;13(8):1331-44. doi: 10.2174/15665240113139990066.
Direct intercellular communication is mediated by gap junctions and their constitutive proteins, the connexins, which are organized in a hexameric arrangement forming a channel between adjacent cells. Connexins are essential for cell homeostasis and are also involved in many physiological processes such as cell growth, differentiation and death. Spermatogenesis is a sophisticated model of germ cell proliferation, differentiation, survival and apoptosis, in which one connexin isoform, connexin 43, plays an essential role as evidenced by the targeted genetic deletion of Cx43 gene. A controlled balance of germ cell growth is a prerequisite to maintain either normal level of spermatozoa necessary for fertility and/or to limit an uncontrolled and anarchic germ cell proliferation, a major risk for germ cell tumor cell development. In the present review, we highlight the emerging role of connexins in testis pathogenesis, specifically in two intimately interconnected human testicular diseases: azoospermia with impaired spermatogenesis and testicular germ cell tumors, whose incidence increased during the last decades. This review proposes the gap junction protein connexin 43 as a new potential cancer diagnostic and prognostic marker, as well as a promising therapeutic target for testicular diseases.
直接细胞间通讯是通过间隙连接及其组成蛋白连接子介导的，连接子以六聚体的形式排列，在相邻细胞之间形成通道。连接子对于细胞内稳态至关重要，并且还参与许多生理过程，如细胞生长、分化和死亡。精子发生是精原细胞增殖、分化、存活和凋亡的复杂模型，其中一种连接子同工型连接子 43（connexin 43，Cx43）起着至关重要的作用，这一点可以通过靶向敲除 Cx43 基因得到证明。精原细胞生长的平衡控制是维持生育所需的正常精子数量或限制不受控制和混乱的精原细胞增殖的前提，后者是生殖细胞肿瘤发生的主要风险因素。在本综述中，我们强调了连接子在睾丸发病机制中的新作用，特别是在两种密切相关的人类睾丸疾病中：精子发生受损导致的无精子症和睾丸生殖细胞肿瘤，这两种疾病在过去几十年中的发病率有所增加。本综述提出间隙连接蛋白连接子 43 作为一种新的潜在癌症诊断和预后标志物，以及睾丸疾病有希望的治疗靶点。
