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Journal of Assisted Reproduction and Genetics

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Open Access 01-02-2020 | Filgrastim | Reproductive Physiology and Disease

A paracrine interaction between granulosa cells and leukocytes in the preovulatory follicle causes the increase in follicular G-CSF levels

Authors: Laure Noël, Maïté Fransolet, Nathalie Jacobs, Jean-Michel Foidart, Michelle Nisolle, Carine Munaut

Published in: Journal of Assisted Reproduction and Genetics | Issue 2/2020

Abstract

Objective

Follicular granulocyte colony-stimulating factor (G-CSF) is a new biomarker of oocyte quality and embryo implantation in in vitro fertilization (IVF) cycles. Its role in reproduction is poorly understood. Our study aimed to investigate the mechanisms and cells responsible for G-CSF production in the preovulatory follicle.

Design

Laboratory research study.

Setting

Single-center study.

Interventions

Granulosa cells and leukocytes were isolated from the follicular fluids (FF) or the blood of women undergoing IVF and from the blood of a control group of women with spontaneous ovulatory cycles to perform cocultures.

Main outcome measure

G-CSF-secreted protein was quantified in the conditioned media of cocultures.

Results

G-CSF secretion was considerably increased in cocultures of granulosa cells and leukocytes. This effect was maximal when leukocytes were isolated from the blood of women in the late follicular phase of the menstrual cycle or from the FF of women undergoing IVF. The leukocyte population isolated from the FF samples of women undergoing IVF had a higher proportion of granulocytes than that isolated from the corresponding blood samples. Leukocytes induced the synthesis and secretion of G-CSF by granulosa cells. Among a range of other FF cytokines/chemokines, only growth-regulated oncogene alpha (GROα) was also increased.

Conclusion

The notable rise in G-CSF at the time of ovulation coincides with the accumulation of follicular granulocytes, which stimulate G-CSF production by granulosa cells via paracrine interactions. High follicular G-CSF concentrations may occur in follicles with optimal granulosa–leukocyte interactions, which could explain the increased implantation rate of embryos arising from these follicles.

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Revelli A, et al. Follicular fluid content and oocyte quality: from single biochemical markers to metabolomics. Reprod Biol Endocrinol. 2009;7:40.PubMedPubMedCentralCrossRef

Coticchio G, Sereni E, Serrao L, Mazzone S, Iadarola I, Borini A. What criteria for the definition of oocyte quality? Ann N Y Acad Sci. 2004;1034:132–44.PubMedCrossRef

Patrizio P, Sakkas D. From oocyte to baby: a clinical evaluation of the biological efficiency of in vitro fertilization. Fertil Steril. 2009;91(4):1061–6.PubMedCrossRef

Stoop D, Ermini B, Polyzos NP, Haentjens P, de Vos M, Verheyen G, et al. Reproductive potential of a metaphase II oocyte retrieved after ovarian stimulation: an analysis of 23 354 ICSI cycles. Hum Reprod. 2012;27(7):2030–5.PubMedCrossRef

Rienzi L, Vajta G, Ubaldi F. Predictive value of oocyte morphology in human IVF: a systematic review of the literature. Hum Reprod Update. 2011;17(1):34–45.PubMedCrossRef

Liu YX, Liu XM, Nin LF, Shi L, Chen SR. Serine protease and ovarian paracrine factors in regulation of ovulation. Front Biosci (Landmark Ed). 2013;18:650–64.CrossRef

Curry TE Jr, Smith MF. Impact of extracellular matrix remodeling on ovulation and the folliculo-luteal transition. Semin Reprod Med. 2006;24(4):228–41.PubMedCrossRef

Espey LL. Ovulation as an inflammatory reaction—a hypothesis. Biol Reprod. 1980;22(1):73–106.PubMedCrossRef

Duffy DM, Ko C, Jo M, Brannstrom M, Curry TE. Ovulation: parallels with inflammatory processes. Endocr Rev. 2019;40(2):369–416.PubMedCrossRef

10.

Demetri GD, Griffin JD. Granulocyte colony-stimulating factor and its receptor. Blood. 1991;78(11):2791–808.PubMedCrossRef

11.

Franzke A. The role of G-CSF in adaptive immunity. Cytokine Growth Factor Rev. 2006;17(4):235–44.PubMedCrossRef

12.

Bendall LJ, Bradstock KF. G-CSF: from granulopoietic stimulant to bone marrow stem cell mobilizing agent. Cytokine Growth Factor Rev. 2014;25(4):355–67.PubMedCrossRef

13.

Rahmati M, et al. Colony stimulating factors 1, 2, 3 and early pregnancy steps: from bench to bedside. J Reprod Immunol. 2015.

14.

Eftekhar M, Naghshineh E, Khani P. Role of granulocyte colony-stimulating factor in human reproduction. J Res Med Sci. 2018;23:7.PubMedPubMedCentralCrossRef

15.

Wurfel W. Treatment with granulocyte colony-stimulating factor in patients with repetitive implantation failures and/or recurrent spontaneous abortions. J Reprod Immunol. 2015;108:123–35.PubMedCrossRef

16.

Robert CA, Abbas MK, Zaidi ARZ, Thiha S, Malik BH. Mediator in the embryo-endometrium cross-talk: granulocyte colony-stimulating factor in infertility. Cureus. 2019;11(8):e5390.PubMedPubMedCentral

17.

Tournaye H, et al. Clinical performance of a specific granulocyte colony stimulating factor ELISA to determine its concentration in follicular fluid as a predictor of implantation success during in vitro fertilization. Gynecol Endocrinol. 2019:1–5.

18.

Makinoda S, Mikuni M, Sogame M, Kobamatsu Y, Furuta I, Yamada H, et al. Erythropoietin, granulocyte-colony stimulating factor, interleukin-1 beta and interleukin-6 during the normal menstrual cycle. Int J Gynaecol Obstet. 1996;55(3):265–71.PubMedCrossRef

19.

Salmassi A, Schmutzler AG, Schaefer S, Koch K, Hedderich J, Jonat W, et al. Is granulocyte colony-stimulating factor level predictive for human IVF outcome? Hum Reprod. 2005;20(9):2434–40.PubMedCrossRef

20.

Hock DL, Huhn RD, Kemmann E. Leukocytosis in response to exogenous gonadotrophin stimulation. Hum Reprod. 1997;12(10):2143–6.PubMedCrossRef

21.

Salmassi A, et al. Detection of granulocyte colony-stimulating factor and its receptor in human follicular luteinized granulosa cells. Fertil Steril. 2004;81(Suppl 1):786–91.PubMedCrossRef

22.

Brannstrom M, Pascoe V, Norman RJ, McClure N. Localization of leukocyte subsets in the follicle wall and in the corpus luteum throughout the human menstrual cycle. Fertil Steril. 1994;61(3):488–95.PubMedCrossRef

23.

Rainey WH, Sawetawan C, Shay JW, Michael MD, Mathis JM, Kutteh W, et al. Transformation of human granulosa cells with the E6 and E7 regions of human papillomavirus. J Clin Endocrinol Metab. 1994;78(3):705–10.PubMed

24.

Shi FT, Cheung AP, Leung PC. Growth differentiation factor 9 enhances activin a-induced inhibin B production in human granulosa cells. Endocrinology. 2009;150(8):3540–6.PubMedCrossRef

25.

Fransolet M, Noël L, Henry L, Labied S, Blacher S, Nisolle M, et al. Evaluation of Z-VAD-FMK as an anti-apoptotic drug to prevent granulosa cell apoptosis and follicular death after human ovarian tissue transplantation. J Assist Reprod Genet. 2019;36(2):349–59.PubMedCrossRef

26.

Havelock JC, Rainey WE, Carr BR. Ovarian granulosa cell lines. Mol Cell Endocrinol. 2004;228(1–2):67–78.PubMedCrossRef

27.

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.PubMedCrossRef

28.

Ledee N, et al. Impact of follicular G-CSF quantification on subsequent embryo transfer decisions: a proof of concept study. Hum Reprod. 2013;28(2):406–13.PubMedCrossRef

29.

Makinoda S, Hirosaki N, Waseda T, Tomizawa H, Fujii R. Granulocyte colony-stimulating factor (G-CSF) in the mechanism of human ovulation and its clinical usefulness. Curr Med Chem. 2008;15(6):604–13.PubMedCrossRef

30.

da Silveira JC, de Ávila ACFCM, Garrett HL, Bruemmer JE, Winger QA, Bouma GJ. Cell-secreted vesicles containing microRNAs as regulators of gamete maturation. J Endocrinol. 2018;236(1):R15–27.PubMedCrossRef

31.

Di Pietro C. Exosome-mediated communication in the ovarian follicle. J Assist Reprod Genet. 2016;33(3):303–11.PubMedPubMedCentralCrossRef

32.

Polec A, et al. Interaction between granulosa-lutein cells and monocytes regulates secretion of angiogenic factors in vitro. Hum Reprod. 2011;26(10):2819–29.PubMedCrossRef

33.

Fedorcsak P, Raki M, Storeng R. Characterization and depletion of leukocytes from cells isolated from the pre-ovulatory ovarian follicle. Hum Reprod. 2007;22(4):989–94.PubMedCrossRef

34.

Loukides JA, Loy RA, Edwards R, Honig J, Visintin I, Polan ML. Human follicular fluids contain tissue macrophages. J Clin Endocrinol Metab. 1990;71(5):1363–7.PubMedCrossRef

35.

Smith MP, Flannery GR, Randle BJ, Jenkins JM, Holmes CH. Leukocyte origin and profile in follicular aspirates at oocyte retrieval. Hum Reprod. 2005;20(12):3526–31.PubMedCrossRef

36.

Hellberg P, Thomsen P, Janson PO, Brännström M. Leukocyte supplementation increases the luteinizing hormone-induced ovulation rate in the in vitro-perfused rat ovary. Biol Reprod. 1991;44(5):791–7.PubMedCrossRef

37.

Ujioka T, Matsukawa A, Tanaka N, Matsuura K, Yoshinaga M, Okamura H. Interleukin-8 as an essential factor in the human chorionic gonadotropin-induced rabbit ovulatory process: interleukin-8 induces neutrophil accumulation and activation in ovulation. Biol Reprod. 1998;58(2):526–30.PubMedCrossRef

38.

Brannstrom M, et al. Reduction of ovulation rate in the rat by administration of a neutrophil-depleting monoclonal antibody. J Reprod Immunol. 1995;29(3):265–70.PubMedCrossRef

39.

Yanagi K, Makinoda S, Fujii R, Miyazaki S, Fujita S, Tomizawa H, et al. Cyclic changes of granulocyte colony-stimulating factor (G-CSF) mRNA in the human follicle during the normal menstrual cycle and immunolocalization of G-CSF protein. Hum Reprod. 2002;17(12):3046–52.PubMedCrossRef

40.

Cai L, Jeon Y, Yoon JD, Hwang SU, Kim E, Park KM, et al. The effects of human recombinant granulocyte-colony stimulating factor treatment during in vitro maturation of porcine oocyte on subsequent embryonic development. Theriogenology. 2015;84(7):1075–87.PubMedCrossRef

41.

Oral E, Seli E, Bahtiyar MO, Jones EE, Arici A. Growth-regulated alpha expression in human preovulatory follicles and ovarian cells. Am J Reprod Immunol. 1997;38(1):19–25.PubMedCrossRef

42.

Karstrom-Encrantz L, et al. Selective presence of the chemokine growth-regulated oncogene alpha (GROalpha) in the human follicle and secretion from cultured granulosa-lutein cells at ovulation. Mol Hum Reprod. 1998;4(11):1077–83.PubMedCrossRef

43.

Haskill S, Peace A, Morris J, Sporn SA, Anisowicz A, Lee SW, et al. Identification of three related human GRO genes encoding cytokine functions. Proc Natl Acad Sci U S A. 1990;87(19):7732–6.PubMedPubMedCentralCrossRef

44.

Baggiolini M, Loetscher P, Moser B. Interleukin-8 and the chemokine family. Int J Immunopharmacol. 1995;17(2):103–8.PubMedCrossRef

45.

Harkin DG, Bignold LP, Herriot-Warnes DM, Kirby CA. Chemotaxis of polymorphonuclear leukocytes towards human pre-ovulatory follicular fluid and serum using a ‘sparse-pore’ polycarbonate filtration membrane. J Reprod Immunol. 1994;27(2):151–5.PubMedCrossRef

46.

Herriot DM, Warnes GM, Kerin JF. Pregnancy-related chemotactic activity of human follicular fluid. Fertil Steril. 1986;45(2):196–201.PubMedCrossRef

Title: A paracrine interaction between granulosa cells and leukocytes in the preovulatory follicle causes the increase in follicular G-CSF levels
Authors: Laure Noël
Maïté Fransolet
Nathalie Jacobs
Jean-Michel Foidart
Michelle Nisolle
Carine Munaut
Publication date: 01-02-2020
Publisher: Springer US
Keywords: Filgrastim
Filgrastim
Published in: Journal of Assisted Reproduction and Genetics / Issue 2/2020
Print ISSN: 1058-0468
Electronic ISSN: 1573-7330
DOI: https://doi.org/10.1007/s10815-020-01692-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

A paracrine interaction between granulosa cells and leukocytes in the preovulatory follicle causes the increase in follicular G-CSF levels

Abstract

Objective

Design

Setting

Interventions

Main outcome measure

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objective

Design

Setting

Interventions

Main outcome measure

Results

Conclusion

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