Karel Souček1,2, Alice Malenovská3, Zuzana Kahounová4,5, Ján Remšík4,5,6, Zuzana Holubcová3,7, Tomáš Soukup8, Daniela Kurfürstová9, Jan Bouchal9, Tereza Suchánková4, Eva Slabáková4, Aleš Hampl10,11. 1. Institute of Biophysics of the Czech Academy of Sciences, Královopolská 135, 612 65, Brno, Czech Republic. ksoucek@ibp.cz. 2. International Clinical Research Center, St. Anne's University Hospital Brno, Brno, Czech Republic. ksoucek@ibp.cz. 3. Reprofit International Clinic of Reproductive Medicine, Brno, Czech Republic. 4. Institute of Biophysics of the Czech Academy of Sciences, Královopolská 135, 612 65, Brno, Czech Republic. 5. International Clinical Research Center, St. Anne's University Hospital Brno, Brno, Czech Republic. 6. Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic. 7. Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Kamenice 3, 625 00, Brno, Czech Republic. 8. Faculty of Medicine in Hradec Králové, Department of Histology and Embryology, Charles University in Prague, Hradec Králové, Czech Republic. 9. Department of Clinical and Molecular Pathology, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic. 10. International Clinical Research Center, St. Anne's University Hospital Brno, Brno, Czech Republic. ahampl@med.muni.cz. 11. Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Kamenice 3, 625 00, Brno, Czech Republic. ahampl@med.muni.cz.
Abstract
PURPOSE: The purpose of the study was to determine whether the GDF-15 is present in follicular fluid; to evaluate if there is a relation between follicular and serum levels of GDF-15 and fertility status of study subjects; and to test whether granulosa cells, oocytes, or both produce GDF-15. METHODS: This study used follicular fluid (FF, serum, and oocytes obtained under informed consent from women undergoing oocyte retrieval for in vitro fertilization. It also used ovaries from deceased preterm newborns. Collection of FF and blood at the time of oocyte retrieval, ELISA and western blot were performed to determine levels and forms of GDF-15. Concentrations of GDF-15 in FF and serum, its expression in ovarian tissue, and secretion from granulosa cells were analyzed. RESULTS: GDF-15 concentration in FF ranged from 35 to 572 ng/ml, as determined by ELISA. Western blot analysis revealed the GDF-15 pro-dimer only in FF. Both normal healthy and cancerous granulosa cells secreted GDF-15 into culture media. Primary oocytes displayed cytoplasmic GDF-15 positivity in immunostained newborn ovaries, and its expression was also observed in fully grown human oocytes. CONCLUSIONS: To the best of our knowledge, this is the first documentation of cytokine GDF-15 presence in follicular fluid. Its concentration was not associated with donor/patient fertility status. Our data also show that GDF-15 is expressed and inducible in both normal healthy and cancerous granulosa cells, as well as in oocytes.
PURPOSE: The purpose of the study was to determine whether the GDF-15 is present in follicular fluid; to evaluate if there is a relation between follicular and serum levels of GDF-15 and fertility status of study subjects; and to test whether granulosa cells, oocytes, or both produce GDF-15. METHODS: This study used follicular fluid (FF, serum, and oocytes obtained under informed consent from women undergoing oocyte retrieval for in vitro fertilization. It also used ovaries from deceased preterm newborns. Collection of FF and blood at the time of oocyte retrieval, ELISA and western blot were performed to determine levels and forms of GDF-15. Concentrations of GDF-15 in FF and serum, its expression in ovarian tissue, and secretion from granulosa cells were analyzed. RESULTS:GDF-15 concentration in FF ranged from 35 to 572 ng/ml, as determined by ELISA. Western blot analysis revealed the GDF-15 pro-dimer only in FF. Both normal healthy and cancerous granulosa cells secreted GDF-15 into culture media. Primary oocytes displayed cytoplasmic GDF-15 positivity in immunostained newborn ovaries, and its expression was also observed in fully grown human oocytes. CONCLUSIONS: To the best of our knowledge, this is the first documentation of cytokine GDF-15 presence in follicular fluid. Its concentration was not associated with donor/patient fertility status. Our data also show that GDF-15 is expressed and inducible in both normal healthy and cancerous granulosa cells, as well as in oocytes.
Authors: Mathias Uhlén; Linn Fagerberg; Björn M Hallström; Cecilia Lindskog; Per Oksvold; Adil Mardinoglu; Åsa Sivertsson; Caroline Kampf; Evelina Sjöstedt; Anna Asplund; IngMarie Olsson; Karolina Edlund; Emma Lundberg; Sanjay Navani; Cristina Al-Khalili Szigyarto; Jacob Odeberg; Dijana Djureinovic; Jenny Ottosson Takanen; Sophia Hober; Tove Alm; Per-Henrik Edqvist; Holger Berling; Hanna Tegel; Jan Mulder; Johan Rockberg; Peter Nilsson; Jochen M Schwenk; Marica Hamsten; Kalle von Feilitzen; Mattias Forsberg; Lukas Persson; Fredric Johansson; Martin Zwahlen; Gunnar von Heijne; Jens Nielsen; Fredrik Pontén Journal: Science Date: 2015-01-23 Impact factor: 47.728
Authors: Linda Yang; Chih-Chuan Chang; Zhe Sun; Dennis Madsen; Haisun Zhu; Søren B Padkjær; Xiaoai Wu; Tao Huang; Karin Hultman; Sarah J Paulsen; Jishu Wang; Anne Bugge; Jane Boesen Frantzen; Per Nørgaard; Jacob Fuglsbjerg Jeppesen; Zhiru Yang; Anna Secher; Haibin Chen; Xun Li; Linu Mary John; Bing Shan; Zhenhua He; Xiang Gao; Jing Su; Kristian T Hansen; Wei Yang; Sebastian Beck Jørgensen Journal: Nat Med Date: 2017-08-28 Impact factor: 53.440
Authors: Lars Wallentin; Ziad Hijazi; Ulrika Andersson; John H Alexander; Raffaele De Caterina; Michael Hanna; John D Horowitz; Elaine M Hylek; Renato D Lopes; Signild Asberg; Christopher B Granger; Agneta Siegbahn Journal: Circulation Date: 2014-10-07 Impact factor: 29.690
Authors: Asne R Bauskin; David A Brown; Simon Junankar; Krishan K Rasiah; Sarah Eggleton; Mark Hunter; Tao Liu; Dave Smith; Tamara Kuffner; Greg J Pankhurst; Heiko Johnen; Pamela J Russell; Wade Barret; Phillip D Stricker; John J Grygiel; James G Kench; Susan M Henshall; Robert L Sutherland; Samuel N Breit Journal: Cancer Res Date: 2005-03-15 Impact factor: 12.701
Authors: Carmen Carrillo-García; Sebastian Prochnow; Ina K Simeonova; Jens Strelau; Gabriele Hölzl-Wenig; Claudia Mandl; Klaus Unsicker; Oliver von Bohlen Und Halbach; Francesca Ciccolini Journal: Development Date: 2014-02 Impact factor: 6.868
Authors: Paul Welsh; Dorien M Kimenai; Riccardo E Marioni; Caroline Hayward; Archie Campbell; David Porteous; Nicholas L Mills; Stephen O'Rahilly; Naveed Sattar Journal: Clin Chem Lab Med Date: 2022-08-18 Impact factor: 8.490
Authors: Pavlína Šimečková; František Hubatka; Jan Kotouček; Pavlína Turánek Knötigová; Josef Mašek; Josef Slavík; Ondrej Kováč; Jiří Neča; Pavel Kulich; Dominik Hrebík; Jana Stráská; Kateřina Pěnčíková; Jiřina Procházková; Pavel Diviš; Stuart Macaulay; Robert Mikulík; Milan Raška; Miroslav Machala; Jaroslav Turánek Journal: Sci Rep Date: 2020-03-16 Impact factor: 4.379