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Reproductive Biology and Endocrinology

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Open Access 01-12-2020 | Estradiol | Research

MiR-423-5p may regulate ovarian response to ovulation induction via CSF1

Authors: Shi Xie, Qiong Zhang, Jing Zhao, Jie Hao, Jing Fu, Yanping Li

Published in: Reproductive Biology and Endocrinology | Issue 1/2020

Abstract

Background

We have previously shown that hsa-miR-423-5p expression in ovarian granulosa cells is decreased in high ovarian response populations. The objective of the present study was to find the target gene and mechanism for miR-423-5p involved in ovarian response regulation.

Methods

(a) TargetScan was used to predict the target gene of hsa-miR-423-5p. (b) A model for hsa-miR-423-5p overexpression or inhibition was constructed by transfecting KGN cells with lentivirus. CSF1 mRNA and protein expression and luciferase activity were measured. (c) The cell cycles of control and lentivirus treated KGN cells were analyzed. Western blot was used to measure the expression of CDKN1A in KGN cells. (d) The concentration of E₂ in KGN cell culture medium were measured.

Results

(a) TargetScan revealed that the 3′ un-translated region of CSF1 matched 11 bases at the 5′ end of miR-423-5p, making it a likely target gene. (b) Overexpression or inhibition of miR-423-5p were associated with respective decreases or increases in CSF1 expression (both mRNA and protein) (p < 0.05) and luciferase activity (p < 0.05). (c) When miR-423-5p expression increased, the number of G0/G1 phase cells and the expression of CDKN1A protein increased while estradiol concentrations in the cell culture solution decreased (p < 0.05). However, when miR-423-5p expression decreased, the number of S phase cells increased and E2 concentrations increased while the expression of CDKN1A protein decreased (p < 0.05).

Conclusions

Colony stimulating factor 1 is a target gene of miR-423-5p and that it may regulate ovarian response to ovulation induction by affecting granulosa cells proliferation and estrogen secretion.

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Rombauts L, Lambalk CB, Schultze-Mosgau A, van Kuijk J, Verweij P, Gates D, et al. Intercycle variability of the ovarian response in patients undergoing repeated stimulation with corifollitropin alfa in a gonadotropin-releasing hormone antagonist protocol. Fertil Steril. 2015;104(4):884–90 e2. https://doi.org/10.1016/j.fertnstert.2015.06.027.CrossRefPubMed

Xie S, Batnasan E, Zhang Q, Li Y. MicroRNA expression is altered in Granulosa cells of ovarian Hyperresponders. Reprod Sci. 2016;23(8):1001–10. https://doi.org/10.1177/1933719115625849.CrossRefPubMed

Yang H, Fu H, Wang B, Zhang X, Mao J, Li X, et al. Exosomal miR-423-5p targets SUFU to promote cancer growth and metastasis and serves as a novel marker for gastric cancer. Mol Carcinog. 2018. https://doi.org/10.1002/mc.22838.

Liu J, Wang X, Yang X, Liu Y, Shi Y, Ren J, et al. miRNA423-5p regulates cell proliferation and invasion by targeting trefoil factor 1 in gastric cancer cells. Cancer Lett. 2014;347(1):98–104. https://doi.org/10.1016/j.canlet.2014.01.024.CrossRefPubMed

Bartel DP. MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281–97. https://doi.org/10.1016/S0092-8674(04)00045-5.CrossRefPubMed

Ambros V. The functions of animal microRNAs. Nature. 2004;431(7006):350–5. https://doi.org/10.1038/nature02871.CrossRefPubMed

Dai A, Sun H, Fang T, Zhang Q, Wu S, Jiang Y, et al. MicroRNA-133b stimulates ovarian estradiol synthesis by targeting Foxl2. FEBS Lett. 2013;587(15):2474–82. https://doi.org/10.1016/j.febslet.2013.06.023.CrossRefPubMed

Fiedler SD, Carletti MZ, Hong X, Christenson LK. Hormonal regulation of MicroRNA expression in periovulatory mouse mural granulosa cells. Biol Reprod. 2008;79(6):1030–7. https://doi.org/10.1095/biolreprod.108.069690.CrossRefPubMedPubMedCentral

Macias S, Michlewski G, Caceres JF. Hormonal regulation of microRNA biogenesis. Mol Cell. 2009;36(2):172–3. https://doi.org/10.1016/j.molcel.2009.10.006.CrossRefPubMed

10.

Sang Q, Yao Z, Wang H, Feng R, Wang H, Zhao X, et al. Identification of microRNAs in human follicular fluid: characterization of microRNAs that govern steroidogenesis in vitro and are associated with polycystic ovary syndrome in vivo. J Clin Endocrinol Metab. 2013;98(7):3068–79. https://doi.org/10.1210/jc.2013-1715.CrossRefPubMed

11.

Xu S, Linher-Melville K, Yang BB, Wu D, Li J. Micro-RNA378 (miR-378) regulates ovarian estradiol production by targeting aromatase. Endocrinology. 2011;152(10):3941–51. https://doi.org/10.1210/en.2011-1147.CrossRefPubMedPubMedCentral

12.

Yao G, Yin M, Lian J, Tian H, Liu L, Li X, et al. MicroRNA-224 is involved in transforming growth factor-beta-mediated mouse granulosa cell proliferation and granulosa cell function by targeting Smad4. Mol Endocrinol. 2010;24(3):540–51. https://doi.org/10.1210/me.2009-0432.CrossRefPubMedPubMedCentral

13.

Wang M, Liu M, Sun J, Jia L, Ma S, Gao J, et al. MicroRNA-27a-3p affects estradiol and androgen imbalance by targeting Creb1 in the granulosa cells in mouse polycytic ovary syndrome model. Reprod Biol. 2017;17(4):295–304. https://doi.org/10.1016/j.repbio.2017.09.005.CrossRefPubMed

14.

Wu S, Sun H, Zhang Q, Jiang Y, Fang T, Cui I, et al. MicroRNA-132 promotes estradiol synthesis in ovarian granulosa cells via translational repression of Nurr1. Reprod Biol Endocrinol. 2015;13:94. https://doi.org/10.1186/s12958-015-0095-z.CrossRefPubMedPubMedCentral

15.

Ahn HW, Morin RD, Zhao H, Harris RA, Coarfa C, Chen ZJ, et al. MicroRNA transcriptome in the newborn mouse ovaries determined by massive parallel sequencing. Mol Hum Reprod. 2010;16(7):463–71. https://doi.org/10.1093/molehr/gaq017.CrossRefPubMedPubMedCentral

16.

Assou S, Al-edani T, Haouzi D, Philippe N, Lecellier CH, Piquemal D, et al. MicroRNAs: new candidates for the regulation of the human cumulus-oocyte complex. Hum Reprod. 2013;28(11):3038–49. https://doi.org/10.1093/humrep/det321.CrossRefPubMed

17.

Carletti MZ, Fiedler SD, Christenson LK. MicroRNA 21 blocks apoptosis in mouse periovulatory granulosa cells. Biol Reprod. 2010;83(2):286–95. https://doi.org/10.1095/biolreprod.109.081448.CrossRefPubMedPubMedCentral

18.

Sirotkin AV, Laukova M, Ovcharenko D, Brenaut P, Mlyncek M. Identification of microRNAs controlling human ovarian cell proliferation and apoptosis. J Cell Physiol. 2010;223(1):49–56. https://doi.org/10.1002/jcp.21999.CrossRefPubMed

19.

Yang X, Zhou Y, Peng S, Wu L, Lin HY, Wang S, et al. Differentially expressed plasma microRNAs in premature ovarian failure patients and the potential regulatory function of mir-23a in granulosa cell apoptosis. Reproduction. 2012;144(2):235–44. https://doi.org/10.1530/REP-11-0371.CrossRefPubMed

20.

Li D, Xu D, Xu Y, Chen L, Li C, Dai X, et al. MicroRNA-141-3p targets DAPK1 and inhibits apoptosis in rat ovarian granulosa cells. Cell Biochem Funct. 2017;35(4):197–201. https://doi.org/10.1002/cbf.3248.CrossRefPubMed

21.

Chen H, Liu C, Jiang H, Gao Y, Xu M, Wang J, et al. Regulatory role of miRNA-375 in expression of BMP15/GDF9 receptors and its effect on proliferation and apoptosis of bovine cumulus cells. Cell Physiol Biochem. 2017;41(2):439–50. https://doi.org/10.1159/000456597.CrossRefPubMed

22.

Du X, Zhang L, Li X, Pan Z, Liu H, Li Q. TGF-beta signaling controls FSHR signaling-reduced ovarian granulosa cell apoptosis through the SMAD4/miR-143 axis. Cell Death Dis. 2016;7(11):e2476. https://doi.org/10.1038/cddis.2016.379.CrossRefPubMedPubMedCentral

23.

Nie M, Yu S, Peng S, Fang Y, Wang H, Yang X. miR-23a and miR-27a promote human granulosa cell apoptosis by targeting SMAD5. Biol Reprod. 2015;93(4):98. https://doi.org/10.1095/biolreprod.115.130690.CrossRefPubMed

24.

Chen X, Xie M, Liu D, Shi K. Downregulation of microRNA146a inhibits ovarian granulosa cell apoptosis by simultaneously targeting interleukin1 receptorassociated kinase and tumor necrosis factor receptorassociated factor 6. Mol Med Rep. 2015;12(4):5155–62. https://doi.org/10.3892/mmr.2015.4036.CrossRefPubMed

25.

Choi Y, Qin Y, Berger MF, Ballow DJ, Bulyk ML, Rajkovic A. Microarray analyses of newborn mouse ovaries lacking Nobox. Biol Reprod. 2007;77(2):312–9. https://doi.org/10.1095/biolreprod.107.060459.CrossRefPubMed

26.

Donadeu FX, Schauer SN, Sontakke SD. Involvement of miRNAs in ovarian follicular and luteal development. J Endocrinol. 2012;215(3):323–34. https://doi.org/10.1530/JOE-12-0252.CrossRefPubMed

27.

Lei L, Jin S, Gonzalez G, Behringer RR, Woodruff TK. The regulatory role of dicer in folliculogenesis in mice. Mol Cell Endocrinol. 2010;315(1–2):63–73. https://doi.org/10.1016/j.mce.2009.09.021.CrossRefPubMed

28.

Liu HC, Tang Y, He Z, Rosenwaks Z. Dicer is a key player in oocyte maturation. J Assist Reprod Genet. 2010;27(9–10):571–80. https://doi.org/10.1007/s10815-010-9456-x.CrossRefPubMedPubMedCentral

29.

Ma J, Flemr M, Stein P, Berninger P, Malik R, Zavolan M, et al. MicroRNA activity is suppressed in mouse oocytes. Curr Biol. 2010;20(3):265–70. https://doi.org/10.1016/j.cub.2009.12.042.CrossRefPubMedPubMedCentral

30.

Nagaraja AK, Andreu-Vieyra C, Franco HL, Ma L, Chen R, Han DY, et al. Deletion of dicer in somatic cells of the female reproductive tract causes sterility. Mol Endocrinol. 2008;22(10):2336–52. https://doi.org/10.1210/me.2008-0142.CrossRefPubMedPubMedCentral

31.

Suh N, Baehner L, Moltzahn F, Melton C, Shenoy A, Chen J, et al. MicroRNA function is globally suppressed in mouse oocytes and early embryos. Curr Biol. 2010;20(3):271–7. https://doi.org/10.1016/j.cub.2009.12.044.CrossRefPubMedPubMedCentral

32.

Sinha PB, Tesfaye D, Rings F, Hossien M, Hoelker M, Held E, et al. MicroRNA-130b is involved in bovine granulosa and cumulus cells function, oocyte maturation and blastocyst formation. J Ovarian Res. 2017;10(1):37. https://doi.org/10.1186/s13048-017-0336-1.CrossRefPubMedPubMedCentral

33.

Dzafic E, Stimpfel M, Virant-Klun I. Plasticity of granulosa cells: on the crossroad of stemness and transdifferentiation potential. J Assist Reprod Gen. 2013;30(10):1255–61. https://doi.org/10.1007/s10815-013-0068-0.CrossRef

34.

Rimon-Dahari N, Yerushalmi-Heinemann L, Alyagor L, Dekel N. Ovarian Folliculogenesis. Results Probl Cell Differ. 2016;58:167–90. https://doi.org/10.1007/978-3-319-31973-5_7.CrossRefPubMed

35.

Andersen CY, Ezcurra D. Human steroidogenesis: implications for controlled ovarian stimulation with exogenous gonadotropins. Reprod Biol Endocrin. 2014;12:128. https://doi.org/10.1186/1477-7827-12-128.CrossRef

36.

Havelock JC, Rainey WE, Carr BR. Ovarian granulosa cell lines. Mol Cell Endocrinol. 2004;228(1–2):67–78. https://doi.org/10.1016/j.mce.2004.04.018.CrossRefPubMed

37.

Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP, Burge CB. Prediction of mammalian microRNA targets. Cell. 2003;115(7):787–98.CrossRefPubMed

38.

Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 2001;25(4):402–8. https://doi.org/10.1006/meth.2001.1262.CrossRefPubMed

39.

Dang W, Qin Z, Fan S, Wen Q, Lu Y, Wang J, et al. miR-1207-5p suppresses lung cancer growth and metastasis by targeting CSF1. Oncotarget. 2016;7(22):32421–32. https://doi.org/10.18632/oncotarget.8718.CrossRefPubMedPubMedCentral

40.

Cimino D, De Pitta C, Orso F, Zampini M, Casara S, Penna E, et al. miR148b is a major coordinator of breast cancer progression in a relapse-associated microRNA signature by targeting ITGA5, ROCK1, PIK3CA, NRAS, and CSF1. FASEB J. 2013;27(3):1223–35. https://doi.org/10.1096/fj.12-214692.CrossRefPubMed

41.

Lagrange B, Martin RZ, Droin N, Aucagne R, Paggetti J, Largeot A, et al. A role for miR-142-3p in colony-stimulating factor 1-induced monocyte differentiation into macrophages. Biochim Biophys Acta. 2013;1833(8):1936–46. https://doi.org/10.1016/j.bbamcr.2013.04.007.CrossRefPubMed

42.

Wang YW, Shi DB, Chen X, Gao C, Gao P. Clinicopathological significance of microRNA-214 in gastric cancer and its effect on cell biological behaviour. PLoS One. 2014;9(3):e91307. https://doi.org/10.1371/journal.pone.0091307.CrossRefPubMedPubMedCentral

43.

Chang HM, Qiao J, Leung PC. Oocyte-somatic cell interactions in the human ovary-novel role of bone morphogenetic proteins and growth differentiation factors. Hum Reprod Update. 2016;23(1):1–18. https://doi.org/10.1093/humupd/dmw039.CrossRefPubMedPubMedCentral

44.

Kranc W, Budna J, Kahan R, Chachula A, Bryja A, Ciesiolka S, et al. Molecular basis of growth, proliferation, and differentiation of mammalian follicular granulosa cells. J Biol Regul Homeost Agents. 2017;31(1):1–8.PubMed

45.

Buscher U, Chen FC, Kentenich H, Schmiady H. Cytokines in the follicular fluid of stimulated and non-stimulated human ovaries; is ovulation a suppressed inflammatory reaction? Hum Reprod. 1999;14(1):162–6.CrossRefPubMed

46.

Terranova PF, Rice VM. Review: cytokine involvement in ovarian processes. Am J Reprod Immunol. 1997;37(1):50–63.CrossRefPubMed

47.

Hume DA, Summers KM, Rehli M. Transcriptional regulation and macrophage differentiation. Microbiol Spectr. 2016;4(3). https://doi.org/10.1128/microbiolspec.MCHD-0024-2015.

48.

Nishimura K, Tanaka N, Ohshige A, Fukumatsu Y, Matsuura K, Okamura H. Effects of macrophage colony-stimulating factor on folliculogenesis in gonadotrophin-primed immature rats. J Reprod Fertil. 1995;104(2):325–30.CrossRefPubMed

49.

Araki M, Fukumatsu Y, Katabuchi H, Shultz LD, Takahashi K, Okamura H. Follicular development and ovulation in macrophage colony-stimulating factor-deficient mice homozygous for the osteopetrosis (op) mutation. Biol Reprod. 1996;54(2):478–84.CrossRefPubMed

50.

Cohen PE, Zhu L, Pollard JW. Absence of colony stimulating factor-1 in osteopetrotic (csfmop/csfmop) mice disrupts estrous cycles and ovulation. Biol Reprod. 1997;56(1):110–8.CrossRefPubMed

51.

Witt BR, Pollard JW. Colony stimulating factor-1 in human follicular fluid. Fertil Steril. 1997;68(2):259–64.CrossRefPubMed

52.

Nishimura K, Tanaka N, Kawano T, Matsuura K, Okamura H. Changes in macrophage colony-stimulating factor concentration in serum and follicular fluid in in-vitro fertilization and embryo transfer cycles. Fertil Steril. 1998;69(1):53–7.CrossRefPubMed

53.

Salmassi A, Zhang Z, Schmutzler AG, Koch K, Buck S, Jonat W, et al. Expression of mRNA and protein of macrophage colony-stimulating factor and its receptor in human follicular luteinized granulosa cells. Fertil Steril. 2005;83(2):419–25. https://doi.org/10.1016/j.fertnstert.2004.06.072.CrossRefPubMed

54.

Salmassi A, Mettler L, Jonat W, Buck S, Koch K, Schmutzler AG. Circulating level of macrophage colony-stimulating factor can be predictive for human in vitro fertilization outcome. Fertil Steril. 2010;93(1):116–23. https://doi.org/10.1016/j.fertnstert.2008.09.083.CrossRefPubMed

55.

Huo L. Analyzining the Effect of Macrophage Colony-Stimulating Factor and Interleukin-1β in Vitro Fertilization-embryo Transfer. Master’s thesis: Zhengzhou University; 2011. http://new.oversea.cnki.net/KCMS/detail/detail.aspx?dbcode=CMFD&dbname=CMFD2012&filename=1011213273.nh&uid=WEEvREcwSlJHSldRa1FhcEFLUmViSGFtTEZiTWFOZXc5VzVjYjdRcnMvND0=$9A4hF_YAuvQ5obgVAqNKPCYcEjKensW4IQMovwHtwkF4VYPoHbKxJw!!&v=MDAwNDFyQ1VSN3FmWStac0ZDcmdXcjdCVkYyNkg3Rz.

56.

Raposo AE, Piller SC. Protein arginine methylation: an emerging regulator of the cell cycle. Cell Div. 2018;13:3. https://doi.org/10.1186/s13008-018-0036-2.CrossRefPubMedPubMedCentral

57.

Huber M, Hadziosmanovic N, Berglund L, Holte J. Using the ovarian sensitivity index to define poor, normal, and high response after controlled ovarian hyperstimulation in the long gonadotropin-releasing hormone-agonist protocol: suggestions for a new principle to solve an old problem. Fertil Steril. 2013;100(5):1270–6. https://doi.org/10.1016/j.fertnstert.2013.06.049.CrossRefPubMed

58.

Zhang Z, Fang Q, Wang J. Involvement of macrophage colony-stimulating factor (M-CSF) in the function of follicular granulosa cells. Fertil Steril. 2008;90(3):749–54. https://doi.org/10.1016/j.fertnstert.2007.06.098.CrossRefPubMed

Title: MiR-423-5p may regulate ovarian response to ovulation induction via CSF1
Authors: Shi Xie
Qiong Zhang
Jing Zhao
Jie Hao
Jing Fu
Yanping Li
Publication date: 01-12-2020
Publisher: BioMed Central
Keyword: Estradiol
Published in: Reproductive Biology and Endocrinology / Issue 1/2020
Electronic ISSN: 1477-7827
DOI: https://doi.org/10.1186/s12958-020-00585-0

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

MiR-423-5p may regulate ovarian response to ovulation induction via CSF1

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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