Follicular fluid expression of alpha-defensins and their role in ovulation

Introduction Defensins are cytotoxic peptides and have a well-defined role in host defense. Human alpha defensins 1–3 (HNP1–3) are primarily produced by peripheral neutrophils and constitute about 50% of the azurphil granule protein. Studies have suggested that peripheral neutrophils and the resident neutrophils in the ovary enhance the release of IL-8 and TNF-α that play a role in ovulation and influence fertilisation rate and IVF outcome. The production of HNP1–3 by follicular fluid and its role in ovulation has never studied. The aim of this study was to demonstrate the presence of HNP1–3 in follicular fluid and to ascertain its correlation with fertilisation rate and IVF outcome.

Women attending the Reproductive Medicine Unit at Liverpool Women’s Hospital UK, for IVF treatment were invited to participate in the study. Sixty-three patients were recruited for the study and underwent controlled ovarian stimulation and oocyte retrieval according to the unit’s protocol. Fluid from the first follicle only was collected to minimise blood contamination of the sample and HNP1–3 was estimated using ELISA technique.

HNP1–3 was detected in follicular fluid samples. The concentration did not correlate with the fertilisation rate (r = 0.01). The concentrations were also not significantly different in the women who did or did not become pregnant following treatment. Subgroup analysis showed that women with endometriosis were not more likely to have higher levels of the HNP1–3 when compared with controls (male factor infertility group).

This is the first study to show the expression of HNP1–3 in follicular fluid. HNP1–3 concentrations did not correlate with fertilisation rate or IVF outcome. It did not show an increased expression of HNP1–3 in fluid collected from women with endometriosis suggesting that inflammatory processes associated with endometriosis do not influence HNP1–3 concentration in the follicular fluid. Further studies to evaluate the correlation between HNP1–3 and IL-8 and TNF-α may clarify the role of defensins in ovulation. Similar content being viewed by others

Ryley HC. Human antimicrobial peptides. Rev Med Microbiol 2001;12(3):177–86. Lehrer RI, Ganz T. Antimicrobial peptides in mammalian and insect host defence. Curr Opin Immunol 1999;11:23–7. Ashitani J, Mukae H, Nakazato M, Taniguchi H, Ogawa K, Kohno S, Matsukura S. Elevated pleural fluid levels of defensins in patients with empyema. Chest 1998;113(3):788–94. Kogan BL, Ganz T, Lehrer RI. Defensins: a family of antimicrobial and cytotoxic peptides. Toxicology 1994;87:131–49. Selsted ME, Szklarek D, Ganz T, et al. Activity of rabbit leucocyte peptides against Candida albicans. Infect Immun 1985;49:202–6. Hancock REW, Diamond G. The role of cationic antimicrobial peptides in innate host defences. Trends Microbiol 2000;8(9):402–10. Arici A, Oral E, Bukulmez O, Buradagunta S, Engin O, Olive DL, et al. interleukin-8 expression and modulation in human preovulatory follicles and ovarian cells. Endocrinol 1996;137:3762–9. Ujioka T, Matsukawa A, Tanaka N, Matsuura K, Yoshinaga M, Okamura H. Interleukin-8 as an essential factor in human chorionic gonadotropin-induced rabbit ovulatory process: interleukin-8 induces neutrophil accumulation and activation in ovulation. Biol Reprod 1998;58:526–30. Hill JA, Welch WR, Faris HM, Anderson DJ. Induction of class II major histocompatibility complex antigen expression in human granulosa cells by interferon gamma: a potential mechanism contributing to autoimmune ovarian failure. Am J Obstet Gynecol 1990;162:534–40. Lei ZM, Chegini N, Rao CHV. Quantitative cell composition of human and ovine copora lutea from various reproductive states. Biol Reprod 1991;44:1148–56. Brannstrom M, Mayrhofer G, Robertson SA. Localisation of leucocyte subsets in the rat ovary during periovulatory period. Biol Reprod 1993;48:277–86. Brannstrom M, Norman RJ. Involvement of leucocytes and cytokines in the ovulatory process and corpus luteum function. Hum Reprod 1993;8(10):1762. Norman RJ, Brannstrom M. Cytokines in the ovary: pathophysiology and potential for pharmacological intervention. Pharmacol Ther 1996;69:219–36. Spanel-Borowski K, Rahner P, Ricken AM. Immunolocalisation of CD-18 positive cells in the bovine ovary. J Reprod Fertil 1997;111:197–205. Spanel-Borowski K, Ricken AM. Evidence for the maintenance of macrophage-like cells in long-term bovine granulosa cell cultures. Cell Tissue Res 1997;288:529–38. Bukulmez O, Arici A. Leucocytes in ovarian function. Hum Reprod Update 2000;6(1):1–15. Takehara Y, Dharmarajan A, Kaufman G, Wallach E. Effect of interleukin-1β on ovulation in the in vitro perfused rabbit ovary. Endocrinology 1997;134:1788–93. Loret de Mola JR, Goldfarb JM, Hecht BR, et al. Gonadotropins induce the release of interleukin 1β, interleukin-6 and tumor necrosis factor-α from the human preovulatory follicle. Am J Reprod Immunol 1998;39:387–90. Karagouni EE, Chryssikopoulos A, Mantzavinos T, Kanakas N, Dotsika EN. Interleukin-1β and interleukin-1α may affect the implantation rate of patients undergoing in vitro fertilisation-embryo transfer. Fertil Steril 1998;70(3):553–9. Herriot DM, Warnes GM, Kerin JF. Pregnancy related chemotactic activity of human follicular fluid. Fertil Steril 1986;45:196–201. Gazvani MR, Bates M, Vince G, Christmas S, Lewis-Jones DI, Kingsland C. Follicular fluid concentrations of IL-12 and IL-8 in IVF cycles. Fertil Steril 2000;74:953–8. Espey LL. Current status of the hypothesis that mammalian ovulation is comparable to an inflammatory reaction. Biol Reprod 1994;49:705–15. Koch AE, Polverini PJ, Kunkel SL, Harlow LA, DiPietro LA, Elner VM, et al. Interleukin-8 as a macrophage derived mediator of angiogenesis. Science 1992;258:1798–801. Author information Authors and Affiliations Corresponding author Appendix Appendix Rights and permissions About this article Cite this article Das, S., Bates, M.D., Vince, G.S. et al. Follicular fluid expression of alpha-defensins and their role in ovulation. J Assist Reprod Genet 25, 83–87 (2008). https://doi.org/10.1007/s10815-007-9197-7 Received: Accepted: Published: Issue date: DOI: https://doi.org/10.1007/s10815-007-9197-7