Investigation of FF-MAS oxysterole’s role in follicular development and its relation to hedgehog signal pathway
Abstract The Hedgehog signaling pathway plays a crucial role in folliculogenesis; however, the association between FF-MAS oxysterol activity in folliculogenesis and the Hedgehog signaling pathway has not been revealed. The evaluation of FF-MAS activity in polycystic ovary syndrome (PCOS) with follic...
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Nature Portfolio
2024-10-01
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| author | Selim Zırh Elham Bahador Zırh Süleyman Erol Lale Karakoç Sökmensüer Gürkan Bozdağ Sevda Fatma Müftüoğlu |
| author_facet | Selim Zırh Elham Bahador Zırh Süleyman Erol Lale Karakoç Sökmensüer Gürkan Bozdağ Sevda Fatma Müftüoğlu |
| author_sort | Selim Zırh |
| collection | DOAJ |
| description | Abstract The Hedgehog signaling pathway plays a crucial role in folliculogenesis; however, the association between FF-MAS oxysterol activity in folliculogenesis and the Hedgehog signaling pathway has not been revealed. The evaluation of FF-MAS activity in polycystic ovary syndrome (PCOS) with folliculogenesis disorder might provide a new approach to tackle follicular and oocyte maturation failure. The question is: does FF-MAS oxysterol affect granulosa cell (GC) proliferation? If so, is this effect facilitated through the Hedgehog pathway? To answer these questions, GCs were isolated from follicle fluids obtained from patients undergoing oocyte retrieval during in vitro fertilization (IVF) treatment. After the isolated GCs were incubated in different cell culture media, the levels of Hedgehog pathway components (SMO, Gli1) were measured by using immunohistochemical methods, cytoELISA, and qRT-PCR. Meanwhile, cell proliferation rates were determined. Significant increases (p < 0.001) in SMO and Gli1 expressions and cell proliferation were observed in the FF-MAS-treated subgroups of both PCOS and male factor participants compared to the FF-MAS deficient subgroup. Remarkably, FF-MAS positively affected the pathway components despite the pathway inhibitor cyclopamine. Although the increase in Hedgehog pathway components was slightly higher in the male factor group (MF), it was not statistically significant. In our study, we demonstrated for the first time the molecular effect of FF-MAS on human GCs in folliculogenesis. Since FF-MAS is already used in assisted reproductive techniques in animals and is known to be synthesized in the human body, it could be considered a new approach in human IVF treatments. |
| format | Article |
| id | doaj-art-55f8d7a0da144fee904b6e00a4f7a552 |
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| issn | 2045-2322 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-55f8d7a0da144fee904b6e00a4f7a5522025-08-20T02:11:18ZengNature PortfolioScientific Reports2045-23222024-10-0114111110.1038/s41598-024-76281-5Investigation of FF-MAS oxysterole’s role in follicular development and its relation to hedgehog signal pathwaySelim Zırh0Elham Bahador Zırh1Süleyman Erol2Lale Karakoç Sökmensüer3Gürkan Bozdağ4Sevda Fatma Müftüoğlu5Faculty of Medicine, Department of Histology and Embryology, Erzincan Binali Yıldırım UniversityFaculty of Medicine, Department of Histology and Embryology, TOBB Economy and Technology UniversityAnkara Etlik Lady Zübeyde Gynaecology Education and Research Hospital, Assisted Reproductive TechniquesFaculty of Medicine, Department of Histology and Embryology, Hacettepe UniversityFaculty of Medicine, Obstetrics and Gynecology, Koç UniversityFaculty of Medicine, Department of Histology and Embryology, Hacettepe UniversityAbstract The Hedgehog signaling pathway plays a crucial role in folliculogenesis; however, the association between FF-MAS oxysterol activity in folliculogenesis and the Hedgehog signaling pathway has not been revealed. The evaluation of FF-MAS activity in polycystic ovary syndrome (PCOS) with folliculogenesis disorder might provide a new approach to tackle follicular and oocyte maturation failure. The question is: does FF-MAS oxysterol affect granulosa cell (GC) proliferation? If so, is this effect facilitated through the Hedgehog pathway? To answer these questions, GCs were isolated from follicle fluids obtained from patients undergoing oocyte retrieval during in vitro fertilization (IVF) treatment. After the isolated GCs were incubated in different cell culture media, the levels of Hedgehog pathway components (SMO, Gli1) were measured by using immunohistochemical methods, cytoELISA, and qRT-PCR. Meanwhile, cell proliferation rates were determined. Significant increases (p < 0.001) in SMO and Gli1 expressions and cell proliferation were observed in the FF-MAS-treated subgroups of both PCOS and male factor participants compared to the FF-MAS deficient subgroup. Remarkably, FF-MAS positively affected the pathway components despite the pathway inhibitor cyclopamine. Although the increase in Hedgehog pathway components was slightly higher in the male factor group (MF), it was not statistically significant. In our study, we demonstrated for the first time the molecular effect of FF-MAS on human GCs in folliculogenesis. Since FF-MAS is already used in assisted reproductive techniques in animals and is known to be synthesized in the human body, it could be considered a new approach in human IVF treatments.https://doi.org/10.1038/s41598-024-76281-5FF-MASFollicle developmentGranulosa cellsOxysterolsPCOSSteroidogenesis |
| spellingShingle | Selim Zırh Elham Bahador Zırh Süleyman Erol Lale Karakoç Sökmensüer Gürkan Bozdağ Sevda Fatma Müftüoğlu Investigation of FF-MAS oxysterole’s role in follicular development and its relation to hedgehog signal pathway Scientific Reports FF-MAS Follicle development Granulosa cells Oxysterols PCOS Steroidogenesis |
| title | Investigation of FF-MAS oxysterole’s role in follicular development and its relation to hedgehog signal pathway |
| title_full | Investigation of FF-MAS oxysterole’s role in follicular development and its relation to hedgehog signal pathway |
| title_fullStr | Investigation of FF-MAS oxysterole’s role in follicular development and its relation to hedgehog signal pathway |
| title_full_unstemmed | Investigation of FF-MAS oxysterole’s role in follicular development and its relation to hedgehog signal pathway |
| title_short | Investigation of FF-MAS oxysterole’s role in follicular development and its relation to hedgehog signal pathway |
| title_sort | investigation of ff mas oxysterole s role in follicular development and its relation to hedgehog signal pathway |
| topic | FF-MAS Follicle development Granulosa cells Oxysterols PCOS Steroidogenesis |
| url | https://doi.org/10.1038/s41598-024-76281-5 |
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