KIT/KIT Ligand in Mammalian Oogenesis and Folliculogenesis: Roles in Rabbit and Murine Ovarian Follicle Activation and Oocyte Growth1

Abstract

In rodent ovaries Kit ligand (KITL) and its receptor KIT have diverse roles, including the promotion of primordial follicle activation, oocyte growth, and follicle survival. Studies were undertaken to determine whether KITL and KIT carry out similar activities in rabbits. KitlandKitmRNA and protein were localized to oocytes and granulosa cells, respectively, in the rabbit ovary. Ovarian cortical explants from juvenile rabbits and neonatal mouse ovaries were subsequently cultured with recombinant mouse KITL and/or KITL neutralizing antibody. Indices of follicle growth initiation were compared with controls and between treatment groups for each species. Recombinant mouse KITL had no stimulatory effect on primordial follicle recruitment in cultured rabbit ovarian explants. However, the mean diameter of oocytes from primordial, early primary, primary, and growing primary follicles increased significantly in recombinant mouse KITL-treated explants compared with untreated tissues. In contrast, recombinant mouse KITL promoted both primordial follicle activation and an increase in the diameter of oocytes from primordial and early primary follicles in the mouse, and these effects were inhibited by coculture with KITL-neutralizing antibody. Recombinant mouse KITL had no effect on follicle survival for either species. These data demonstrate that KITL promotes the growth of rabbit and mouse oocytes and stimulates primordial follicle activation in the mouse but not in the rabbit. We propose that the physiologic roles of KITL and KIT may differ between species, and this has important implications for the design of in vitro culture systems for folliculogenesis in mammals, including the human.

KIT receptor-positive cells in the bovine corpus luteum are primarily theca-derived small luteal cells

“…In addition, a subpopulation of KITC monocytes are detectable in the septum/capsule area of the bovine CL of early development. Further studies are needed to corroborate whether, similar to the promotion of follicular development by the KIT-KIT ligand complex (Carlsson et al 2006, Hutt et al 2006, the CL life cycle also depends on KIT and KIT ligand-expressing cells.…”

Transcriptional control of KIT gene expression during germ cell development

“…The full-length KIT protein is also expressed in post-natal oocytes, and several reports indicate that it is important for their growth and maturation (Packer et al, 1994;Kissel et al, 2000;Klinger and De Felici, 2002;Hutt et al, 2006).…”

Oocyte-dependent activation of MTOR in cumulus cells controls the development and survival of cumulus–oocyte complexes

“…Bi-directional communication between the oocyte and its companion granulosa cells is a crucial factor in this coordination. Granulosa cells promote oocyte growth and global silencing of transcription (De La Fuente and Eppig, 2001;Hutt et al, 2006), maintain oocyte meiotic arrest and mediate the resumption of meiosis induced by the preovulatory luteinizing hormone surge , whereas signals from oocytes promote granulosa cell proliferation and differentiation by coordinating with signals induced by folliclestimulating hormone (FSH) (Diaz et al, 2007a;El-Hefnawy and Zeleznik, 2001;Gilchrist et al, 2001;Latham et al, 2004;Li et al, 1995;Vanderhyden et al, , 1992, suppress granulosa cell apoptosis and premature luteinization (Eppig et al, 1997;Hussein et al, 2005;Orisaka et al, 2006), and enable expansion of the cumulus cell population and ovulation Joyce et al, 2001). …”