Abstract
Purpose
β-defensins are antimicrobial peptides expressed at mucosal level of male and female genito-urinary tract, where they exert protective functions against infections, possibly preserving human health and fertility. In our study, we investigated the possible involvement of β-defensins in female and male infertility in Italian infertile couples (i) evaluating the presence of human β-defensin 1 (hBD-1) in follicular fluid (FF) and its correlation with in vitro fertilization (IVF) outcomes; (ii) investigating the relationship between hBD-1 levels in semen and IVF outcomes (comprising correlation with sperm parameters); and (iii) exploring the effect of hBD-1 peptide on spermatozoa motility in vitro.
Methods
A perspective observational analytic pilot study was conducted. hBD-1 concentration was measured with ELISA assay in FF and semen from 50 couples that underwent assisted procreation technique procedures due to infertility status. Moreover, hBD-1 exogenous peptide was administered to 29 normozoospermic semen and their motility was recorded.
Results
hBD-1 was detected in FF and its levels were significantly higher in women with good fertilization rate (≥ 75%), respect to those with a poor fertilization rate (< 75%). The hBD-1 semen concentrations in oligo-asthenozoospermic subjects were significantly lower than that in normozoospermic men. Instead, hBD-1 level in sperm and FF not correlated with pregnancy rate. Finally, incubation of sperm with exogenous hBD-1 significantly increased progressive motility after 1 h and 24 h.
Conclusions
Being aware of the relatively small sample size and medium power, our results possibly suggest that hBD-1 could influence oocyte and sperm quality, and could improve, when exogenously added, sperm motility.
Similar content being viewed by others
References
Baecher-Lind LE, Miller WC, Wilcox AJ. Infectious disease and reproductive health: a review. Obstet Gynecol Surv. 2010;65:53–65.
Horne AW, Stock SJ, King AE. Innate immunity and disorders of the female reproductive tract. Reproduction. 2008;135:739–49.
Sheldon IM, Owens S-E, Turner ML. Innate immunity and the sensing of infection, damage and danger in the female genital tract. J Reprod Immunol. 2017;119:67–73.
Easton DM, Nijnik A, Mayer ML, Hancock REW. Potential of immunomodulatory host defense peptides as novel anti-infectives. Trends Biotechnol. 2009;27:582–90.
Jarczak J, Kościuczuk EM, Lisowski P, Strzałkowska N, Jóźwik A, Horbańczuk J, et al. Defensins: natural component of human innate immunity. Hum Immunol. 2013;74:1069–79.
Sheldon IM, Bromfield JJ. Innate immunity in the human endometrium and ovary. Am J Reprod Immunol. 2011;66(Suppl 1):63–71.
Raschig J, Mailänder-Sánchez D, Berscheid A, Berger J, Strömstedt AA, Courth LF, et al. Ubiquitously expressed human beta defensin 1 (hBD1) forms bacteria-entrapping nets in a redox dependent mode of action. PLoS Pathog. 2017;13:e1006261.
King AE, Kelly RW, Sallenave J-M, Bocking AD, Challis JRG. Innate immune defences in the human uterus during pregnancy. Placenta. 2007;28:1099–106.
Com E, Bourgeon F, Evrard B, Ganz T, Colleu D, Jégou B, et al. Expression of antimicrobial defensins in the male reproductive tract of rats, mice, and humans. Biol Reprod. 2003;68:95–104.
Dorin JR, Barratt CLR. Importance of β-defensins in sperm function. Mol Hum Reprod. 2014;20:821–6.
Diao R, Fok KL, Chen H, Yu MK, Duan Y, Chung CM, et al. Deficient human β-defensin 1 underlies male infertility associated with poor sperm motility and genital tract infection. Sci Transl Med. 2014;6:249ra108.
Corson SL, Batzer FR, Marmar J, Maislin G. The human sperm-hamster egg penetration assay: prognostic value. Fertil Steril. 1988;49:328–34.
World Health Organization. WHO laboratory manual for the examination and processing of human semen. 5th ed. Geneva: World Health Organization; 2010.
Ricci G, Perticarari S, Boscolo R, Simeone R, Martinelli M, Fischer-Tamaro L, et al. Leukocytospermia and sperm preparation--a flow cytometric study. Reprod Biol Endocrinol. 2009;7:128.
Ricci G, Granzotto M, Luppi S, Giolo E, Martinelli M, Zito G, et al. Effect of seminal leukocytes on in vitro fertilization and intracytoplasmic sperm injection outcomes. Fertil Steril. 2015;104:87–93.
Ferraretti AP, La Marca A, Fauser BCJM, Tarlatzis B, Nargund G, Gianaroli L, et al. ESHRE consensus on the definition of “poor response” to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011;26:1616–24.
Oehninger S, Coddington CC, Scott R, Franken DA, Burkman LJ, Acosta AA, et al. Hemizona assay: assessment of sperm dysfunction and prediction of in vitro fertilization outcome. Fertil Steril. 1989;51:665–70.
Veeck L. Preembryo grading and degree of cytoplasmic fragmentation. An atlas of human gametes and conceptuses: an illustrated reference for assisted reproductive technology. New York: Parthenon Publishing; 1999.
Gardner D, Schoolcraft W. In vitro culture of human blastocysts. In: Toward reproductive certainty: fertility and genetics beyond. London: Parthenon Publishing; 1999. p. 378–88.
Zegers-Hochschild F, Adamson GD, Dyer S, Racowsky C, de Mouzon J, Sokol R, et al. The international glossary on infertility and fertility care, 2017. Fertil Steril. 2017;108:393–406.
Zegers-Hochschild F, Adamson GD, Dyer S, Racowsky C, de Mouzon J, Sokol R, et al. The international glossary on infertility and fertility care, 2017†‡§. Hum Reprod. 2017;32:1786–801.
R core Team. R: a language and environment for statistical computing [Internet]. Vienna, Austria. 2018. Available from: http://www.R-project.org
Faul F, Erdfelder E, Lang A-G, Buchner A. G*power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007;39:175–91.
von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP, et al. The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol. 2008;61:344–9.
Yoshimura Y. Avian β-defensins expression for the innate immune system in hen reproductive organs. Poult Sci. 2015;94:804–9.
Rodgers RJ, Irving-Rodgers HF. Formation of the ovarian follicular antrum and follicular fluid. Biol Reprod. 2010;82:1021–9.
Semple F, Dorin JR. β-defensins: multifunctional modulators of infection, inflammation and more? J Innate Immun. 2012;4:337–48.
Weiss G, Goldsmith LT, Taylor RN, Bellet D, Taylor HS. Inflammation in reproductive disorders. Reprod Sci. 2009;16:216–29.
Sheldon IM, Cronin JG, Healey GD, Gabler C, Heuwieser W, Streyl D, et al. Innate immunity and inflammation of the bovine female reproductive tract in health and disease. Reproduction. 2014;148:R41–51.
Boots CE, Jungheim ES. Inflammation and human ovarian follicular dynamics. Semin Reprod Med. 2015;33:270–5.
Abramov Y, Schenker JG, Lewin A, Friedler S, Nisman B, Barak V. Plasma inflammatory cytokines correlate to the ovarian hyperstimulation syndrome. Hum Reprod. 1996;11:1381–6.
Calippe B, Douin-Echinard V, Delpy L, Laffargue M, Lélu K, Krust A, et al. 17Beta-estradiol promotes TLR4-triggered proinflammatory mediator production through direct estrogen receptor alpha signaling in macrophages in vivo. J Immunol. 2010;185:1169–76.
Han JH, Kim MS, Lee MY, Kim TH, Lee M-K, Kim HR, et al. Modulation of human beta-defensin-2 expression by 17beta-estradiol and progesterone in vaginal epithelial cells. Cytokine. 2010;49:209–14.
Das S, Bates MD, Vince GS, Lewis-Jones I, Gazvani R. Follicular fluid expression of alpha-defensins and their role in ovulation. J Assist Reprod Genet. 2008;25:83–7.
Das S, Vince GS, Lewis-Jones I, Bates MD, Gazvani R. The expression of human alpha and beta defensin in the endometrium and their effect on implantation. J Assist Reprod Genet. 2007;24:533–9.
Caballero-Campo P, Buffone MG, Benencia F, Conejo-García JR, Rinaudo PF, Gerton GL. A role for the chemokine receptor CCR6 in mammalian sperm motility and chemotaxis. J Cell Physiol. 2014;229:68–78.
Bedaiwy M, Shahin AY, AbulHassan AM, Goldberg JM, Sharma RK, Agarwal A, et al. Differential expression of follicular fluid cytokines: relationship to subsequent pregnancy in IVF cycles. Reprod BioMed Online. 2007;15:321–5.
Sarapik A, Velthut A, Haller-Kikkatalo K, Faure GC, Béné M-C, de Carvalho BM, et al. Follicular proinflammatory cytokines and chemokines as markers of IVF success. Clin Dev Immunol. 2012;2012:606459.
Tollner TL, Venners SA, Hollox EJ, Yudin AI, Liu X, Tang G, et al. A common mutation in the defensin DEFB126 causes impaired sperm function and subfertility. Sci Transl Med. 2011;3:92ra65.
Funding
This work was supported by University of Trieste – “University funding for scientific research project “(U22SCFRA15) and by IRCCS Burlo Garofolo/Italian Ministry of Health (RC 15/2017 and RC 18/2016).
Author information
Authors and Affiliations
Contributions
LZ performed the statistical analyses and wrote the manuscript. VP performed hBD-1 ELISA experiments. MM, SL, and EG collected the samples, participated in patients enrollment, and revised the manuscript. GZ and FR enrolled the participants, were responsible of patients clinical management, and collected the samples. LS supervised the experiments, revised the manuscript, and contributed in the study design. SC conceived the study and critically revised the manuscript. GR conceived the study, was responsible for the management of patients, and critically revised the manuscript.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no competing interests.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
ESM 1
(DOCX 14 kb)
Rights and permissions
About this article
Cite this article
Zupin, L., Polesello, V., Martinelli, M. et al. Human β-defensin 1 in follicular fluid and semen: impact on fertility. J Assist Reprod Genet 36, 787–797 (2019). https://doi.org/10.1007/s10815-019-01409-w
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10815-019-01409-w