Transforming growth factor β signaling pathway regulating the function of follicle stimulating hormone in ovarian granulosa cells

WANG Yu-tong WEI Xiao-hong GE Ling YANG Yun-feng XU Jian

Acta Anatomica Sinica ›› 2021, Vol. 52 ›› Issue (1) : 118-123.

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Acta Anatomica Sinica ›› 2021, Vol. 52 ›› Issue (1) : 118-123. DOI: 10.16098/j.issn.0529-1356.2021.01.019
Histology,Embryology and Developmental Biology

 Transforming growth factor β signaling pathway regulating the function of follicle stimulating hormone in ovarian granulosa cells

  • WANG Yu-tong WEI Xiao-hong GE Ling YANG Yun-feng XU Jian*
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Abstract

Objective  To explore the interaction between follicle stimulating hormone (FSH) and transforming growth factor Beta (TGF-β) signaling pathway in rat ovarian granulosa cells.    Methods  The granulosa cells isolated from the follicles of 21 days SD rats. The experiments were divided into three groups: control group, FSH treated group and transforming growth factor beta receptor Ⅱ (TGF-β RⅡ) neutralizated group. Immunocytochemistry (ICC) and Western blotting were then used to locate and detect the expression level of TGF-β RⅡ and proliferating cell nuclear antigen (PCNA). The proliferation index (PI), cell cycle and percentage of apoptotic cells were assessed by flow cytometry (FCM), and the level of estradiol (E2) was determined by ELISA.   Results  FSH increased the expression of PCNA and PI, changed the cell cycle and inhibited apoptosis of GCs, and these actions were reduced significantly when TGF-βsignaling pathway was inhibited(P<0.05); FSH stimulated the secretion of E2, and the increase in E2 levels was not regulated by inhibition of the TGF-β signaling pathway(P>0.05).   Conclusion  The effects of FSH on ovarian granulosa cells are partly affected by the TGF-β signaling pathway.

Key words

Granulosa cells culture / Follicle stimulating hormone / Transforming growth factor β / Immunohistochemistry / Western blotting / Rat

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WANG Yu-tong WEI Xiao-hong GE Ling YANG Yun-feng XU Jian.  Transforming growth factor β signaling pathway regulating the function of follicle stimulating hormone in ovarian granulosa cells[J]. Acta Anatomica Sinica. 2021, 52(1): 118-123 https://doi.org/10.16098/j.issn.0529-1356.2021.01.019

References

[1] Ocon-Grove OM, Poole DH, Johnson AL. Bone morphogenetic protein 6 promotes FSH receptor and anti-Müllerian hormone mRNA expression in granulosa cells from hen prehierarchal follicles [J]. Reproduction (Cambridge, England), 2012, 143(6): 825-833.
[2] Mcgee EA, Oakley JI, Xu J. Transforming growth factor β (TGF-β) and activin stimulate nuclear translocation of Smad proteins in granulosa cells [J]. Fertil Steril, 2001, 76(3): S38.
[3] Gueripel X, Benahmed M, Gougeon A. Sequential gonadotropin treatment of immature mice leads to amplification of transforming growth factor beta action, via upregulation of receptor-type 1, Smad 2 and 4, and downregulation of Smad 6 [J]. Biol Reprod, 2004, 70(3): 640-648.
[4] Wei XH, Qi LH, Xu J, et al. The effects of FSH on the phosphorylation of Smad2/Smad3 protein in rat ovarian granulosa cells[J].Chinese Journal of Anatomy, 2008, 31(2): 141-144.(in Chinese)
卫晓红, 祁丽花, 徐健,等. 卵泡刺激素调节大鼠卵巢颗粒细胞中Smad2/Smad3蛋白的表达及磷酸化[J]. 解剖学杂志, 2008, 31(2): 141-144.
[5] Dong JX, Wei XH, Xu J, et al. Establishment of an in vitro blocking model of transforming growth factor beta signal transduction pathway in ovarian granulosa cells [J].Chinese Journal of Anatomy, 2008, 31(1):128-129.(in Chinese)
董静霞,卫晓红,徐健,等. 体外阻断卵巢颗粒细胞转化生长因子β信号转导通路模型的建立 [J]. 解剖学杂志, 2008, 31(1):128-129.
[6] Kossowska-Tomaszczuk K, De Geyter C, De Geyter M, et al. The multipotency of luteinizing granulosa cells collected from mature ovarian follicles [J]. Stem cells (Dayton, Ohio), 2009, 27(1): 210-219.
[7] Shen ChY, Dong JX, Xu J. Smad3 promotes the autophagy of granulosa cells in rats[J]. Acta Anatomica Sinica, 2014, 45(1): 109-113.(in Chinese)
申春艳, 董静霞, 徐健. Smad3促进大鼠卵巢颗粒细胞自噬 [J]. 解剖学报, 2014, 45(1): 109-113.
[8] Visser JA, Schipper Ⅰ, Laven JSE, et al. Anti-Müllerian hormone: an ovarian reserve marker in primary ovarian insufficiency [J]. Nat Rev Endocrinol, 2012, 8(6): 331-341.
[9] Pigny P, Merlen E, Robert Y, et al. Elevated serum level of anti-mullerian hormone in patients with polycystic ovary syndrome: relationship to the ovarian follicle excess and to the follicular arrest [J]. J Clin Endocrinol Metab, 2003, 88(12): 5957-5962.
[10] Chang HM, Qiao J, Leung PCK. Oocyte-somatic cell interactions in the human ovary-novel role of bone morphogenetic proteins and growth differentiation factors [J]. Hum Reprod Update, 2016, 23(1): 1-18.
[11] Zafeiriou S, Loutradis D, Michalas S. The role of gonadotropins in follicular development and their use in ovulation induction protocols for assisted reproduction [J]. Eur J Contracept Reprod Health Care, 2000, 5(2): 157-167.
[12] Liu YC, Marraccino RL, Keng PC, et al. Requirement for proliferating cell nuclear antigen expression during stages of the Chinese hamster ovary cell cycle [J]. Biochemistry, 1989, 28(7): 2967-2974.
[13] Sun XF, Sun XH, Cheng SF, et al. Interaction of the transforming growth factor-β and Notch signaling pathways in the regulation of granulosa cell proliferation [J]. Reprod Fertil Dev, 2016, 28(12): 1873-1881.
[14] Liu Y, Chen X, Xue X, et al. Effects of Smad3 on the proliferation and steroidogenesis in human ovarian luteinized granulosa cells [J]. IUBMB Life, 2014, 66(6): 424-437.
[15] Wang D, Di X, Wang J, et al. Increased formation of follicular antrum in aquaporin-8-deficient mice is due to defective proliferation and migration, and not steroidogenesis of granulosa cells [J]. Front Physiol, 2018, 9:1193.
[16] Tomic D, Miller KP, Kenny HA, et al. Ovarian follicle development requires Smad3 [J]. Mol Endocrinol, 2004, 18(9): 2224-2240.
[17] Gong X, Mcgee EA. Smad3 is required for normal follicular follicle-stimulating hormone responsiveness in the mouse [J]. Biol Reprod, 2009, 81(4): 730-738.
[18] Shen M, Jiang Y, Guan Z, et al. Protective mechanism of FSH against oxidative damage in mouse ovarian granulosa cells by repressing autophagy [J]. Autophagy, 2017, 13(8): 1364-1385.
[19] Boone DL, Tsang BK. Identification and localization of deoxyribonuclease Ⅰ in the rat ovary [J]. Biol Reprod, 1997, 57(4): 813-821.
[20] Li Y, Jin Y, Liu Y, et al. SMAD3 regulates the diverse functions of rat granulosa cells relating to the FSHR/PKA signaling pathway [J]. Reproduction (Cambridge, England), 2013, 146(2): 169-179.
[21] Bernard DJ, Tran S. Mechanisms of activin-stimulated FSH synthesis: the story of a pig and a FOX [J]. Biol Reprod, 2013, 88(3): 78.
[22] Bendell JJ, Dorrington J. Estradiol-17 beta stimulates DNA synthesis in rat granulosa cells: action mediated by transforming growth factor-beta [J]. Endocrinology, 1991, 128(5): 2663-2665.
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