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The effects of CLP-induced sepsis on proliferation and apoptosis of granulosa and theca cells in rat ovary: A histochemical and ultrastructural study
Institution:1. Istanbul University, Istanbul Faculty of Medicine, Department of Histology and Embryology, Istanbul 34093, Turkey;2. Istanbul University, Istanbul Faculty of Medicine, Department of Laboratory Animal, Aziz Sancar Institute of Experimental Medicine, Istanbul 34093, Istanbul, Turkey;3. Istanbul University, Istanbul Faculty of Medicine, Department of Neuroscience, Aziz Sancar Institute of Experimental Medicine, Istanbul 34093, Istanbul, Turkey;4. Istanbul University, Istanbul Faculty of Medicine, Department of Medical Pathology, Istanbul 34093, Turkey;5. Istanbul University, Istanbul Faculty of Medicine, Department of Forensic Medicine, Istanbul 34093, Turkey;6. Istanbul University, Istanbul Faculty of Medicine, Department of Physiology, Istanbul 34093, Turkey;1. Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, P.O.Box: 1177, Urmia, Iran;2. Department of Surgery and Diagnostic Imaging, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran;3. Department of Microbiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran;1. Department of Obstetrics and Gynecology, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Istanbul, Turkey;2. Department of Obstetrics and Gynecology, Reyap Hospital Corlu, Tekirdag, Turkey;3. Department of Biochemistry, Yildiz Technical University, Istanbul, Turkey;4. Department of Biochemistry, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Istanbul, Turkey;5. Department of Obstetrics and Gynecology, Memorial Bahcelievler Hospital, Istanbul, Turkey;6. Department of Physiology, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Istanbul, Turkey;1. Department of Urology, Krankenhaus Hietzing mit Neurologischem Zentrum Rosenhügel, Vienna, Austria;2. Department of Laboratory Medicine, Krankenhaus Hietzing mit Neurologischem Zentrum Rosenhügel, Vienna, Austria;3. Karl Landsteiner Institute for Clinical Risk Management, Vienna, Austria;4. Department of Urology, Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust, Bournemouth, United Kingdom;5. Department of Surgery, University of Cambridge, Cambridge, United Kingdom;1. The Fertility Center from A to Z, Affiliated with Assuta Medical Center, Tel Aviv, Israel;2. The Fertility Clinic, Skive Regional Hospital, Denmark;3. Faculty of Health, Aarhus University, Denmark;4. The Sackler Faculty of Medicine, Tel Aviv University, P.O.B 39040, Tel Aviv, Israel;1. Faculty of Medicine, Universiti Teknologi MARA Sungai Buloh Campus, Selangor, Malaysia;2. I-PPerFORM, Universiti Teknologi MARA, Malaysia;1. Department of Urology, St. Marianna University of Medicine, 2 -16-1 Sugao, Miyamae, Kawasaki, Kanagawa, 216-8511, Japan;2. College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa, Kanagawa 252-0890, Japan;3. Laboratory of Animal Reproduction, Faculty of Bioscience and Bioindustry, Tokushima University, Ishii, Myozai-gun, Tokushima, 779-3233, Japan
Abstract:Sepsis is defined as a systemic inflammatory response to infection. This study is aimed to evaluate the effects of experimental sepsis on the proliferation and apoptosis of granulosa and theca cells in the rat ovary.28-day-old immature Wistar-Albino female rats were treated with pregnant mare serum gonadotrophin to develop the first generation of preovulatory follicles. Sepsis was induced by cecal ligation and puncture (CLP). Following in vivo 5-Bromo-2-deoxyuridine (BrdU) labeling, animals were sacrificed and ovaries were embedded in paraffin and Epon. Besides electron microscopic evaluation, BrdU, cleaved caspase-3, p27 immunostaining, and TUNEL labeling were performed.In CLP-operated animals, cleaved caspase-3 immunoreactivity was significantly increased in Graafian follicles. TUNEL and BrdU labeling in the ovarian follicles were not statistically different between CLP and sham-operated rats. In septic animals, p27 immunoreactivity was increased significantly in the nuclei of oocytes and decreased in the cytoplasm of granulosa and theca cells in multilaminar primary follicles compared to the sham group. In ultrastructural evaluation, increased apoptosis was observed in theca interna and granulosa cells in both the early and late stages of follicles in the CLP group.In conclusion, experimentally-induced sepsis leads to apoptosis in ovarian follicles at advanced stages of development. Our data suggest that although sepsis may not cause a potential threat to developing follicles at least in the short term, more severe damage may occur during advanced stages of follicle development.
Keywords:Sepsis  Cecal ligation  Puncture  Folliculogenesis  Ovary  Apoptosis
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