title: p27 and its ubiquitin ligase Skp2 expression in endometrium of IVF patients with repeated hormonal stimulation.
abstract: This preliminary study examined a possible effect of long duration repeated hormonal stimulation on the endometrium using a molecular tool. The expression of the hormone stimulated, cell cycle regulators, p27 and its ligase S-phase kinase-interacting protein2 (Skp2), were assessed in 46 endometrial samples of patients who underwent repeated IVF cycles (3-21). Skp2 protein is usually undetectable in normal tissue and can be demonstrated only in rapidly dividing cells. Samples from non-stimulated, normal cycling women served as control group A. Samples of endometrial carcinoma served as control group B. In secretory endometrium, the expression of p27 was found to be lower and Skp2 higher in the study group compared with control group A. Moreover, in 25% of patients of the study group, Skp2 expression was significantly higher (P < 0.05) compared with control group A, reaching concentrations demonstrated in endometrial carcinoma. The findings of this study suggest that repeated hormone stimulation cycles may disrupt endometrial physiology, potentially towards abnormal proliferation. These changes in protein expression are described for the first time in IVF patients and should be further investigated.
authors.affiliation: Departments of Obstetrics and Gynecology, IVF Unit, Lady Davis Carmel Medical Center, Haifa, Israel. Electronic address: lahav_shirly@clalit.org.il.
authors.forename: Shirly
authors.initials: S
authors.lastname: Lahav-Baratz
authors.affiliation: Departments of Obstetrics and Gynecology, IVF Unit, Lady Davis Carmel Medical Center, Haifa, Israel.
authors.forename: Mara
authors.initials: M
authors.lastname: Koifman
authors.affiliation: Department of Pathology, Rambam Medical Center, Haifa, Israel; The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Edmond
authors.initials: E
authors.lastname: Sabo
authors.affiliation: Departments of Obstetrics and Gynecology, IVF Unit, Lady Davis Carmel Medical Center, Haifa, Israel; The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Ron
authors.initials: R
authors.lastname: Auslender
authors.affiliation: Departments of Obstetrics and Gynecology, IVF Unit, Lady Davis Carmel Medical Center, Haifa, Israel; The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Martha
authors.initials: M
authors.lastname: Dirnfeld
mesh_terms: D000328:Adult; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016889:Endometrial Neoplasms / Q000378:metabolism / Q000473:pathology; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008596:Menotropins / Q000009:adverse effects / Q000627:therapeutic use; D017274:Nafarelin / Q000009:adverse effects / Q000627:therapeutic use; D010062:Ovulation Induction; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism*
chemical_list: D044786:S-Phase Kinase-Associated Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D017274:Nafarelin; D008596:Menotropins; D005640:Follicle Stimulating Hormone
keywords: IVF; endometrium; ovulation induction; p27; ubiquitin