title: Kit ligand and c-Kit are expressed during early human ovarian follicular development and their interaction is required for the survival of follicles in long-term culture.
abstract: The receptor tyrosine c-Kit and its cognate ligand, c-Kit ligand (KL, stem cell factor, SCF), are involved in ovarian follicular development in several animal species. We studied the expression of KL and c-Kit using in situ hybridization and immunohistochemistry in donated human ovarian cortical tissue. The KL transcripts were expressed in granulosa cells of primary follicles, whereas the expression of c-Kit was confined to the oocyte and granulosa cells in primary and secondary follicles. We employed an ovarian organ culture using firstly serum-containing and then serum-free medium to study the effects of KL and an anti-c-Kit antibody, ACK2, on the development and survival of ovarian follicles in vitro. Culture of ovarian cortical slices for 7 days resulted in a 37% increase in the number of primary follicles and a 6% increase in secondary follicles. The proportion of viable follicles decreased in all cultures. The addition of KL (1, 10 and 100 ng/ml) into the culture media did not affect the developmental stages of the follicles or the proportion of atretic follicles. Inclusion of ACK2 (800 ng/ml) in the culture medium significantly increased the proportion of atretic follicles on days 7 (49 vs 28% in control cultures) and 14 (62 vs 38%) of culture. In conclusion, c-Kit and KL are expressed in human ovaries during follicular development. Blocking the c-Kit receptor induces follicular atresia. The KL/c-Kit signaling system is likely to control the survival of human ovarian follicles during early follicular development.
authors.affiliation: Karolinska Institutet, Department of Clinical Science, Intervention and Technology. Karolinska University Hospital, Stockholm, Sweden. Inger.Britt.Carlsson@klinvet.ki.se
authors.forename: Inger B
authors.initials: IB
authors.lastname: Carlsson
authors.forename: Mika P E
authors.initials: MP
authors.lastname: Laitinen
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Scott
authors.forename: Henna
authors.initials: H
authors.lastname: Louhio
authors.forename: Louiza
authors.initials: L
authors.lastname: Velentzis
authors.forename: Timo
authors.initials: T
authors.lastname: Tuuri
authors.forename: Johanna
authors.initials: J
authors.lastname: Aaltonen
authors.forename: Olli
authors.initials: O
authors.lastname: Ritvos
authors.forename: Robert M L
authors.initials: RM
authors.lastname: Winston
authors.forename: Outi
authors.initials: O
authors.lastname: Hovatta
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015152:Blotting, Northern / Q000379:methods; D005260:Female; D005496:Follicular Atresia; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D009924:Organ Culture Techniques; D006080:Ovarian Follicle / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis* / Q000276:immunology / Q000378:metabolism; D019089:Stem Cell Factor / Q000032:analysis* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit