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The effect of GnRH antagonist cetrorelix on Wnt signaling members in pubertal and adult mouse ovaries

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Abstract

Wide application of gonadotropin-releasing hormone (GnRH) agonists and antagonists for clinical purposes determines their effects on ovarian signaling pathways. Our study aimed to determine the localization, expression levels of Wnt signaling members in the pubertal and adult mouse ovary and the impact of GnRH antagonist cetrorelix on these signaling members. 0.5 mg/kg of cetrorelix was injected to 3-and 6-week-old mice for 2 weeks. At the end of injection, ovaries from 5 (5Ce)- to 8-week (8Ce)-old mice were embedded in paraffin for immunohistochemistry and homogenized for western blot to compare with control (5C–8C) and sham groups (5S–8S). WNT2 and WNT4 showed higher expression in thecal and stromal cells in adult mouse ovaries and only WNT4 expression was affected by cetrorelix. FZD1 was localized mainly in oocytes of pubertal ovaries and granulosa cells and oocytes of adult ovaries. FZD1 was reduced by cetrorelix in pubertal ovaries. FZD4 was abundantly localized in thecal and stromal cells of all groups and protein level was not affected by cetrorelix. LRP-6 was expressed mainly in oocytes and stromal cells of pubertal, oocytes of adult ovaries and its expression was reduced by cetrorelix in adult ovaries. CTNNB1 intensity in granulosa cells was the lowest in pubertal and the highest in adult ovaries and its expression was decreased by cetrorelix in adult ovaries. Cetrorelix affected the expression of specific members of the Wnt signaling depending on the developmental stage of mice, pointing out its possible interaction with gonadotropins during pubertal and adult stages.

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Acknowledgements

This study was supported by the Scientific Research Projects Coordination Unit of Akdeniz University (Project Number: 2012.01.0103.003).

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Authors and Affiliations

  1. Department of Histology and Embryology, Faculty of Medicine, Akdeniz University, Campus, 07070, Antalya, Turkey

    Filiz Tepekoy, Fatma Uysal, Nuray Acar, Ismail Ustunel & Gokhan Akkoyunlu

  2. Department of Histology and Embryology, Faculty of Medicine, Altinbas University, 34147, Istanbul, Turkey

    Filiz Tepekoy

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  1. Filiz Tepekoy
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  2. Fatma Uysal
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  3. Nuray Acar
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  4. Ismail Ustunel
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  5. Gokhan Akkoyunlu
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Contributions

FT and FU carried out cetrorelix injections, tissue processing, and immunohistochemistry experiments and performed evaluation and the statistical analysis for immunohistochemistry. FT and NA applied western blot experiments and performed the statistical analysis for western blot results. IU and GA conceived of the study, participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.

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Correspondence to Gokhan Akkoyunlu.

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Tepekoy, F., Uysal, F., Acar, N. et al. The effect of GnRH antagonist cetrorelix on Wnt signaling members in pubertal and adult mouse ovaries. Histochem Cell Biol 152, 423–437 (2019). https://doi.org/10.1007/s00418-019-01817-0

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