title: Expression and regulation of the tumor suppressor, SEF, during folliculogenesis in humans and mice.
abstract: Similar expression to FGF (Sef or IL17-RD), is a tumor suppressor and an inhibitor of growth factors as well as of pro-inflammatory cytokine signaling. In this study, we examined the regulation of Sef expression by gonadotropins during ovarian folliculogenesis. In sexually immature mice, in situ hybridization (ISH) localized Sef gene expression to early developing oocytes and granulosa cells (GC) but not to theca cells. Sef was also expressed in mouse ovarian endothelial cells, in the fallopian tube epithelium as well as in adipose tissue venules. SEF protein expression, determined by immunohistochemistry (IHC), correlated well with Sef mRNA expression in GC, while differential expression was noticed in oocytes. High Sef mRNA but undetectable SEF protein levels were observed in the oocytes of primary/secondary follicles, while an inverse correlation was found in the oocytes of preantral and small antral follicles. Sef mRNA expression dropped after pregnant mare's serum gonadotropin (PMSG) administration, peaked at 6-8 h after human chorionic gonadotropin (hCG) treatment, and declined by 12 h after this treatment. ISH and IHC localized the changes to oocytes and mural GC following PMSG treatment, whereas Sef expression increased in mural GC and declined in granulosa-lutein cells upon hCG treatment. The ovarian expression of SEF was confirmed using human samples. ISH localized SEF transcripts to human GC of antral follicles but not to corpora lutea. Furthermore, SEF mRNA was detected in human GC recovered from preovulatory follicles. These results are the first to demonstrate SEF expression in a healthy ovary during folliculogenesis. Hormonal regulation of its expression suggests that SEF may be an important factor involved in intra-ovarian control mechanisms.
authors.affiliation: Department of BiologyTechnion, Israel Institute of Technology, 32000 Haifa, IsraelFaculté de Médecine VétérinaireCentre de Recherche en Reproduction Animale, Université de Montréal, St-Hyacinthe, Quebec, CanadaDepartment of Biological RegulationThe Weizmann Institute of Science, Rehovot, IsraelIVF UnitDepartment of Obstetrics and Gynecology, Kaplan Medical Center (Affiliated to the Medical School of the Hebrew University and Hadassah, Jerusalem), Rehovot, Israel.
authors.forename: Ela
authors.initials: E
authors.lastname: Lutwak
authors.affiliation: Department of BiologyTechnion, Israel Institute of Technology, 32000 Haifa, IsraelFaculté de Médecine VétérinaireCentre de Recherche en Reproduction Animale, Université de Montréal, St-Hyacinthe, Quebec, CanadaDepartment of Biological RegulationThe Weizmann Institute of Science, Rehovot, IsraelIVF UnitDepartment of Obstetrics and Gynecology, Kaplan Medical Center (Affiliated to the Medical School of the Hebrew University and Hadassah, Jerusalem), Rehovot, Israel.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Price
authors.affiliation: Department of BiologyTechnion, Israel Institute of Technology, 32000 Haifa, IsraelFaculté de Médecine VétérinaireCentre de Recherche en Reproduction Animale, Université de Montréal, St-Hyacinthe, Quebec, CanadaDepartment of Biological RegulationThe Weizmann Institute of Science, Rehovot, IsraelIVF UnitDepartment of Obstetrics and Gynecology, Kaplan Medical Center (Affiliated to the Medical School of the Hebrew University and Hadassah, Jerusalem), Rehovot, Israel.
authors.forename: Sagit-Sela
authors.initials: SS
authors.lastname: Abramovich
authors.affiliation: Department of BiologyTechnion, Israel Institute of Technology, 32000 Haifa, IsraelFaculté de Médecine VétérinaireCentre de Recherche en Reproduction Animale, Université de Montréal, St-Hyacinthe, Quebec, CanadaDepartment of Biological RegulationThe Weizmann Institute of Science, Rehovot, IsraelIVF UnitDepartment of Obstetrics and Gynecology, Kaplan Medical Center (Affiliated to the Medical School of the Hebrew University and Hadassah, Jerusalem), Rehovot, Israel.
authors.forename: Shiri
authors.initials: S
authors.lastname: Rabinovitz
authors.affiliation: Department of BiologyTechnion, Israel Institute of Technology, 32000 Haifa, IsraelFaculté de Médecine VétérinaireCentre de Recherche en Reproduction Animale, Université de Montréal, St-Hyacinthe, Quebec, CanadaDepartment of Biological RegulationThe Weizmann Institute of Science, Rehovot, IsraelIVF UnitDepartment of Obstetrics and Gynecology, Kaplan Medical Center (Affiliated to the Medical School of the Hebrew University and Hadassah, Jerusalem), Rehovot, Israel.
authors.forename: Irit
authors.initials: I
authors.lastname: Granot
authors.affiliation: Department of BiologyTechnion, Israel Institute of Technology, 32000 Haifa, IsraelFaculté de Médecine VétérinaireCentre de Recherche en Reproduction Animale, Université de Montréal, St-Hyacinthe, Quebec, CanadaDepartment of Biological RegulationThe Weizmann Institute of Science, Rehovot, IsraelIVF UnitDepartment of Obstetrics and Gynecology, Kaplan Medical Center (Affiliated to the Medical School of the Hebrew University and Hadassah, Jerusalem), Rehovot, Israel.
authors.forename: Nava
authors.initials: N
authors.lastname: Dekel
authors.affiliation: Department of BiologyTechnion, Israel Institute of Technology, 32000 Haifa, IsraelFaculté de Médecine VétérinaireCentre de Recherche en Reproduction Animale, Université de Montréal, St-Hyacinthe, Quebec, CanadaDepartment of Biological RegulationThe Weizmann Institute of Science, Rehovot, IsraelIVF UnitDepartment of Obstetrics and Gynecology, Kaplan Medical Center (Affiliated to the Medical School of the Hebrew University and Hadassah, Jerusalem), Rehovot, Israel dinar@tx.technion.ac.il.
authors.forename: Dina
authors.initials: D
authors.lastname: Ron
mesh_terms: D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D005260:Female; D005299:Fertility Agents / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D006064:Gonadotropins, Equine / Q000494:pharmacology; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism*
chemical_list: D006063:Chorionic Gonadotropin; D005299:Fertility Agents; D006064:Gonadotropins, Equine; C477526:IL17RD protein, human; D008565:Membrane Proteins; D012333:RNA, Messenger; D018123:Receptors, Interleukin; C469338:Sef protein, mouse