title: Expression and regulation of sFRP family members in human granulosa cells.
abstract: Follicular development and ovulation are major processes in the reproductive system. Understanding their complexity is important to female fertility treatments and the control of reproductive processes. Wnt signaling pathway components were shown to be involved in reproduction in animal models. The secreted frizzled-related protein-4 (sFRP4), a potential modulator of Wnt4 signaling pathway, was shown to be induced by LH in rodents and expressed in the corpus lutea, but the pattern of its expression in human ovaries remains unknown. We evaluated the expression pattern of sFRP4 and other sFRP family members in human mural and cumulus granulosa cells (GCs), as well as their regulation by LH/hCG. GCs were obtained from follicles aspirated during in vitro maturation and IVF procedures. GCs were also plated and grown in culture. We showed that the human sFRP4 expression decreases as follicles grows to the preovulatory stage and its expression was higher in cumulus GCs than in mural GCs. Interestingly, LH/hCG stimulation of GCs in vivo and in culture resulted in decreased expression of sFRP4. Of the other sFRP family members, sFRP5 expression was found in mural and cumulus GC in vivo and was shown to be induced by LH/hCG in vitro and in vivo. In summary, sFRP4 is expressed in human GCs and its expression declines during late antral follicular growth. sFRP4 expression is also inhibited by LH/hCG, unlike its rodent homolog. In human GC, sFRP5 may substitute the role of sFRP4 in mouse GC.
authors.affiliation: IVF Unit and Human Embryonic Stem Cell and Reproduction Lab, Department of Obstetrics and Gynecology, Sheba Medical Center, Tel Hashomer 52621 Israel.
authors.forename: Ettie
authors.initials: E
authors.lastname: Maman
authors.forename: Yuval
authors.initials: Y
authors.lastname: Yung
authors.forename: Berta
authors.initials: B
authors.lastname: Cohen
authors.forename: Sarah
authors.initials: S
authors.lastname: Konopnicki
authors.forename: Mariabeatrice
authors.initials: M
authors.lastname: Dal Canto
authors.forename: Rubens
authors.initials: R
authors.lastname: Fadini
authors.forename: Hannah
authors.initials: H
authors.lastname: Kanety
authors.forename: Alon
authors.initials: A
authors.lastname: Kedem
authors.forename: Jehoshua
authors.initials: J
authors.lastname: Dor
authors.forename: Ariel
authors.initials: A
authors.lastname: Hourvitz
mesh_terms: D000328:Adult; D054885:Cumulus Cells / Q000378:metabolism*; D005260:Female; D006801:Humans; D006080:Ovarian Follicle; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D011518:Proto-Oncogene Proteins; C118723:SFRP4 protein, human; D000094742:Secreted Frizzled-Related Proteins