Follicular atresia is the term used for the fate of follicles which undergo degenerative changes before rupturing during ovulation. Recent studies suggest that granulosa cell apoptosis play a major role in follicular atresia. The factors which lead the cell to apoptosis and which protect the cell death, still remain complicated and more studies are needed to elucidate the whole process. Here in this review, we aimed to simplify the factors and mechanisms taking place in granulosa cell apoptosis, to make the process more understandable.Key words: Granulosa cell, apoptosis, follicular atresia.
INTRODUCTÄ°ONWhen a female human embryo is 8-week-old, she has 600,000 germ cells in her gonads and this number increases to 6 to 7 million at 20 weeks of gestation. But with the increasing rate of atresia, the number declines progressively and 1 million oocytes are present in the newborn, whereas 300,000 oocytes remain in puberty, of which approximately 400 will ovulate during the fertile lifespan (Oktem and Oktay, 2008;Gougeon, 1996;Matova and Cooley, 2001).'Follicular atresia' term is used to define antral follicles undergoing degenerative changes before rupturing during ovulation. It is initiated within the granulosa cell layer and subsequently in the theca cells Hsueh et al., 1994). In mammals, the basic mechanism of follicular atresia is apoptosis (Depalo et al., 2003). Apoptosis is a way which multicellular organisms use to eliminate unwanted cells in response to developmental signals or toxic stimuli (Quirck et al., 2004). It is regulated at the level of transcription or translation (Manabe et al., 2008). Major morphological characteristics of apoptosis are the internucleosomal DNA fragmentation, cell shrinkage, plasma membrane blebbing, and the apoptotic body formation (Schwartzman and Cidlowski, 1993).Granulosa cells possess endogenous pathways to trigger apoptosis, that are inhibited in the presence of survi-*Corresponding author. E-mail: zebru33@gmail.com. Tel: +90 (312) 2158652. Fax: +90 (312) 3124931.val factors (Quirck et al., 2004). To date, many apoptosisrelated factors have been implicated in follicular atresia, including death ligands and receptors, Bcl-2 family proteins, Nodal, caspases, growth factors, gonadotropins, and calcium. In this report, we will overview these factors one by one.
Proapoptotic regulators in the cell death receptorligand systemDeath receptors constitute a subgroup within the tumor necrosis factor (TNF) receptor family. They are located on the cell surface, anchored to the cell membrane, are trimerized and have cytoplasmic death domains (DDs) which are necessary to induce apoptosis (Park et al., 2005;Ashkenazi and Dixit, 1998;Wallach et al., 1999). Fas receptor, TNF receptor, and TNF related apoptosis inducing ligand receptors (TRAILr) are the members of TNF receptor family that are found to have roles in follicular atresia in mammalian ovaries (Park et al., 2005).In most of the cases, the cell death receptor-mediated apoptosis takes place as follows:1) The cell death ligand binds to...