title: KIT signaling regulates primordial follicle formation in the neonatal mouse ovary.
abstract: The pool of primordial follicles determines the reproductive lifespan of the mammalian female, and its establishment is highly dependent upon proper oocyte cyst breakdown and regulation of germ cell numbers. The mechanisms controlling these processes remain a mystery. We hypothesized that KIT signaling might play a role in perinatal oocyte cyst breakdown, determination of oocyte numbers and the assembly of primordial follicles. We began by examining the expression of both KIT and KIT ligand in fetal and neonatal ovaries. KIT was expressed only in oocytes during cyst breakdown, but KIT ligand was present in both oocytes and somatic cells as primordial follicles formed. To test whether KIT signaling plays a role in cyst breakdown and primordial follicle formation, we used ovary organ culture to inhibit and activate KIT signaling during the time when these processes occur in the ovary. We found that when KIT was inhibited, there was a reduction in cyst breakdown and an increase in oocyte numbers. Subsequent studies using TUNEL analysis showed that when KIT was inhibited, cell death was reduced. Conversely, when KIT was activated, cyst breakdown was promoted and oocyte numbers decreased. Using Western blotting, we found increased levels of phosphorylated MAP Kinase when KIT ligand was added to culture. Taken together, these results demonstrate a role for KIT signaling in perinatal oocyte cyst breakdown that may be mediated by MAP Kinase downstream of KIT.
authors.affiliation: Department of Biology, Syracuse University, Syracuse, NY 13244, USA.
authors.forename: Robin L
authors.initials: RL
authors.lastname: Jones
authors.forename: Melissa E
authors.initials: ME
authors.lastname: Pepling
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count; D016923:Cell Death; D004789:Enzyme Activation; D005260:Female; D005333:Fetus / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D006080:Ovarian Follicle / Q000166:cytology / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D019089:Stem Cell Factor
chemical_list: D019089:Stem Cell Factor; D011065:Poly(ADP-ribose) Polymerases; D019009:Proto-Oncogene Proteins c-kit; D020928:Mitogen-Activated Protein Kinases
keywords: Cyst breakdown; Follicle formation; KIT signaling; Oocyte survival