Ascidians: New Model Organisms for Reproductive Endocrinology

Ovarian functions, including growth of oocytes and follicles, are believed to involve coordinated and multistep biological events that undergo functional regulation by a wide range of endogenous factors. Mammalian follicles consist of one oocyte surrounded by granulosa cells and theca cells (Orisaka et al., 2009). Mammalian follicular growth is basically classified into two phases: gonadotropin-independent and gonadotropindependent stages. The former includes early follicular growth stages, namely, primordial, primary, secondary, preantral, and antral stages, whereas follicle recruitment, selection, and ovulation occur during the latter. A great variety of intraovarian and extraovarian factors such as a pituitary hormone, gonadotropin, have been well structurally and functionally elucidated. In contrast, no signaling molecules responsible for gonadotropin-independent oocyte growth have ever been identified. ”Neuropeptides” and ”non-sexual peptide hormones” are promising candidates for regulators of early follicle growth, given that many of their receptors were found to be expressed in the ovary. Nevertheless, biological effects of neuropeptides and non-sexual hormones on the ovary still remain controversial or unknown. Such inconclusive data resulted primarily from the difficulty in elucidating in vitro and in vivo physiological functions of neuropeptides or non-sexual hormones in the mammalian ovaries due to heterogeneous quality of oocytes (the very small number of successfully growing oocytes), the low basal levels of receptor expression, and complicated sexual periods (Candenas et al., 2005; Satake & Kawada, 2006a; Debejuk, 2006; Wang & Sun 2007). Furthermore, most receptors of peptide ligands are not ubiquitously, but widely expressed, and thus, neuropeptides and peptide hormones have multiple biological roles, which frequently caused great difficulties in discriminating direct actions on the ovary from indirect actions of a peptide during functional analyses via in vivo administration or using a peptideand/or a receptor-knockout mouse. In such cases, model studies using lower organisms, such as a fruitfly Drosophila melanogaster or a nematode Caenorhabditis elegans, may be useful as the primary step for studies on the biological sciences of mammals. Nevertheless, most invertebrate neuropeptides and hormones possess species-specific primary structures and biological activities. This has hindered comparative analysis and application of traditional invertebrate models to neuroscience and endocrinology research involving neuropeptides and hormones in mammals. These issues suggest a potential