Johnson Alan L, Bridgham Jamie T
Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556, USA.
Reproduction. 2002 Jul;124(1):19-27. doi: 10.1530/rep.0.1240019.
In the vertebrate ovary, apoptosis is the process by which excess or non-viable germ and granulosa cells are eliminated early in ontogeny (often beginning before birth), and thereafter continuously throughout reproductive life. Accordingly, an excessively high rate or abnormal triggering of such cell death (and, by implication, follicle atresia) can negatively affect fertility. Programmed cell death involves the integration of many pathways and intracellular proteins, and central among these at almost every stage are members of the caspase family. Relatively little attention has been focused upon the ovary with regards to elucidating initiator and effector members of the caspase family, and pathways by which they are activated and inactivated. The present review briefly describes vertebrate caspases and the regulation of their function in non-ovarian tissues. Subsequently, the status of caspase expression and function in orchestrating apoptotic cell death in ovarian germ and follicle somatic cells is considered. The most compelling results implicating specific caspases in ovarian function have been derived from mouse single and double knockout model systems. The final outcome of continued studies, in addition to providing information regarding understanding and management of infertility, will influence the development of strategies to treat ovarian cancers and ameliorate the adverse effects of their therapy (for example, chemotherapy).
在脊椎动物卵巢中，细胞凋亡是一个过程，通过该过程，过量或无活力的生殖细胞和颗粒细胞在个体发育早期（通常在出生前就开始）被清除，此后在整个生殖生命过程中持续进行。因此，这种细胞死亡（以及由此暗示的卵泡闭锁）的过高发生率或异常触发会对生育能力产生负面影响。程序性细胞死亡涉及许多信号通路和细胞内蛋白质的整合，几乎在每个阶段，半胱天冬酶家族成员都是其中的核心。在阐明半胱天冬酶家族的起始和效应成员以及它们被激活和失活的信号通路方面，相对较少关注卵巢。本综述简要描述了脊椎动物半胱天冬酶及其在非卵巢组织中功能的调节。随后，考虑了半胱天冬酶在协调卵巢生殖细胞和卵泡体细胞凋亡性细胞死亡中的表达和功能状态。涉及特定半胱天冬酶在卵巢功能中的最引人注目的结果来自小鼠单基因和双基因敲除模型系统。持续研究的最终结果，除了提供有关不孕症理解和管理的信息外，还将影响治疗卵巢癌和减轻其治疗（例如化疗）不良反应的策略的制定。
