Skip to main content

Advertisement

SpringerLink
Log in

Association between neuropeptide oxytocin and male infertility

  • Gonadal Physiology and Disease
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

To investigate the relationship between oxytocin (OT) and male infertility, serum OT baseline concentration and oxytocin receptor (OTR) gene expression in fertile and infertile men were investigated.

Methods and patients

Twenty obstructive azoospermia patients, twenty five idiopathic asthenozoospermia patients, twenty idiopathic oligozoospermia patients and twenty healthy subjects were taken into consideration. Serum OT baseline concentration was determined by radioimmunoassay. Moreover, serum concentration of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone (T) were determined by chemoluminescence to evaluate the correlation with OT. OTR gene promotor and OTR mRNA expressions were determined by polymerase chain reaction and reverse transcriptase-polymerase chain reaction, respectively. OTR protein expression was also performed by Western Blot.

Results

Serum OT baseline concentrations in infertile groups were significantly higher than in fertile group (F0.05/2(2,82) = 8.29, p < 0.001). Serum baseline concentration of OT was not correlated with that of LH, FSH and T. There was no significant difference in gene sequences of OTR gene promotor and OTR mRNA when comparing infertile patients with fertile. Human OTR was in the form of oligomers and monomers, and the oligomers were in the majority containing tetramers and hexamers. Monomer expression was significantly higher in idiopathic asthenozoospermia and idiopathic oligozoospermia than that in obstructive azoospermia and control group (F0.05/2(2,82) = 115.50, p < 0.001). There was no significant difference in oligomer expression between different groups, but 20% of idiopathic asthenozoospermia cases showed a decrease.

Conclusions

Significantly different OT baseline concentrations and OTR expressions between fertile and infertile men strongly suggest that OT/OTR system is likely to be linked with male infertility, providing new insights into the pathogenesis and treatment of male infertility.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Thackare H, Nicholson HD, Whittington K. Oxytocin—its role in male reproduction and new potential therapeutic uses. Hum Reprod Update. 2006;12:437–48.

    Article  CAS  PubMed  Google Scholar 

  2. Frayne J, Nicholson HD. Localization of oxytocin receptors in the human and macaque monkey male reproductive tracts: evidence for a physiological role of oxytocin in the male. Mol Hum Reprod. 1998;4:527–32.

    Article  CAS  PubMed  Google Scholar 

  3. Filippi S, Vannelli GB, Granchi S, Luconi M, Crescioli C, Mancina R, et al. Identification, localization and functional activity of oxytocin receptors in epididymis. Mol Cell Endocrinol. 2002;193:89–100.

    Article  CAS  PubMed  Google Scholar 

  4. Whittington K, Assinder S, Gould M, Nicholson H. Oxytocin, oxytocin-associated neurophysin and the oxytocin receptor in the human prostate. Cell Tissue Res. 2004;318:375–82.

    Article  CAS  PubMed  Google Scholar 

  5. Vignozzi L, Vannelli GB, Morelli A, Mancina R, Marini M, Ferruzzi P, et al. Identification, characterization and biological activity of oxytocin receptor in the developing human penis. Mol Hum Reprod. 2005;11:99–106.

    Article  CAS  PubMed  Google Scholar 

  6. Hoare S, Copland JA, Strakova Z, Ives K, Jeng YJ, Hellmich MR, et al. The proximal portion of the COOH terminus of the oxytocin receptor is required for coupling to g(q), but not g(i). Independent mechanisms for elevating intracellular calcium concentrations from intracellular stores. J Biol Chem. 1999;274:28682–9.

    Article  CAS  PubMed  Google Scholar 

  7. Zhong M, Parish B, Murtazina DA, Ku C-Y, Sanborn BM. Amino acids in the COOH-terminal region of the oxytocin receptor third intracellular domain are important for receptor function. Am J Physiol Endocrinol Metab. 2007;292:E977–84.

    Article  CAS  PubMed  Google Scholar 

  8. WHO. Laboratory manual for the examination of human semen and sperm-cervical mucus interaction. 4th ed. Cambridge: Cambridge University Press; 1999.

    Google Scholar 

  9. Abdalla S, Lother H, el Massiery A, Quitterer U. Increased AT(1) receptor heterodimers in preeclampsia mediate enhanced angiotensin II responsiveness. Nat Med. 2001;7:1003–9.

    Article  CAS  PubMed  Google Scholar 

  10. Li J, You Z, Chen Z, Song C, Lu C. Chronic morphine treatment inhibits oxytocin release from the supraoptic nucleus slices of rats. Neurosci Lett. 2001;300:54–8.

    Article  CAS  PubMed  Google Scholar 

  11. Kusui C, Kimura T, Ogita K, Nakamura H, Matsumura Y, Koyama M, et al. DNA methylation of the human oxytocin receptor gene promoter regulates tissue-specific gene suppression. Biochem Biophys Res Commun. 2001;289:681–6.

    Article  CAS  PubMed  Google Scholar 

  12. Carmichael MS, Warburton VL, Dixen J, Davidson JM. Relationships among cardiovascular, muscular, and oxytocin responses during human sexual activity. Arch Sex Behav. 1994;23:59–79.

    Article  CAS  PubMed  Google Scholar 

  13. Assinder SJ, Johnson C, King K, Nicholson HD. Regulation of 5{alpha}-reductase isoforms by oxytocin in the rat ventral prostate. Endocrinology. 2004;145:5767–73.

    Article  CAS  PubMed  Google Scholar 

  14. Rives ML, Vol C, Fukazawa Y, Tinel N, Trinquet E, Ayoub MA, et al. Crosstalk between GABA(B) and mGlu1a receptors reveals new insight into GPCR signal integration. EMBO J. 2009;28:2195–208.

    Article  CAS  PubMed  Google Scholar 

  15. Cottet M, Albizu L, Perkovska S, Jean-Alphonse F, Rahmeh R, Orcel H, et al. Past, present and future of vasopressin and oxytocin receptor oligomers, prototypical GPCR models to study dimerization processes. Curr Opin Pharmacol. 2010;10:59–66.

    Article  CAS  PubMed  Google Scholar 

  16. Stein DJ. Oxytocin and vasopressin: social neuropeptides. CNS Spectr. 2009;14:602–6.

    PubMed  Google Scholar 

  17. Tobias E, George BS. The neurobiology of stress management. Neuro Endocrinol Lett. 2010;31:30.

    Google Scholar 

  18. Marsh AA, Yu HH, Pine DS, Blair RJR. Oxytocin improves specific recognition of positive facial expressions. Psychopharmacology (Berl). 2010;209:225–32.

    Article  CAS  Google Scholar 

  19. Prichard ZM, Mackinnon AJ, Jorm AF, Easteal S. AVPR1A and OXTR polymorphisms are associated with sexual and reproductive behavioral phenotypes in humans. Mutation in brief no. 981. Online. Hum Mutat. 2007;28:1150.

    Article  PubMed  Google Scholar 

  20. Costa B, Pini S, Gabelloni P, Abelli M, Lari L, Cardini A, et al. Oxytocin receptor polymorphisms and adult attachment style in patients with depression. Psychoneuroendocrinology. 2009;34:1506–14.

    Article  CAS  PubMed  Google Scholar 

  21. Mehta MK, Garde SV, Sheth AR. Occurrence of FSH, inhibin and other hypothalamic-pituitary-intestinal hormones in normal fertility, subfertility, and tumors of human testes. Int J Fertil Menopausal Stud. 1995;40:39–46.

    CAS  PubMed  Google Scholar 

  22. Ramasamy R, Lin K, Gosden LV, Rosenwaks Z, Palermo GD, Schlegel PN. High serum FSH levels in men with nonobstructive azoospermia does not affect success of microdissection testicular sperm extraction. Fertil Steril. 2009;92:590–3.

    Article  CAS  PubMed  Google Scholar 

  23. Warne DW, Decosterd G, Okada H, Yano Y, Koide N, Howles CM. A combined analysis of data to identify predictive factors for spermatogenesis in men with hypogonadotropic hypogonadism treated with recombinant human follicle-stimulating hormone and human chorionic gonadotropin. Fertil Steril. 2009;92:594–604.

    Article  CAS  PubMed  Google Scholar 

  24. Dimitrios GG, Christos T, Paschalia KI, Paris P, Persefoni-Dimitra K, Basil CT, et al. Serum inhibin B and anti-Müllerian hormone are not superior to follicle-stimulating hormone as predictors of the presence of sperm in testicular fine-needle aspiration in men with azoospermia. Fertil Steril. 2009;91:1279–84.

    Article  Google Scholar 

  25. Robinson G, Evans JJ, Forster ME. Oxytocin can affect follicular development in the adult mouse. Acta Endocrinol (Copenh). 1985;108:273–6.

    CAS  Google Scholar 

  26. Wathes DC, Swann RW, Pickering BT. Variations in oxytocin, vasopressin and neurophysin concentrations in the bovine ovary during the oestrous cycle and pregnancy. J Reprod Fertil. 1984;71:551–7.

    Article  CAS  PubMed  Google Scholar 

  27. Kirilov G, Saharieva S, Javorska N. The inability of oxytocin to influence the secretion of testosterone, prolactin, luteinizing and follicle-stimulating hormone in normal men. Exp Clin Endocrinol. 1986;88:115–8.

    Article  CAS  PubMed  Google Scholar 

  28. Devost D, Zingg H. Identification of dimeric and oligomeric complexes of the human oxytocin receptor by co-immunoprecipitation and bioluminescence resonance energy transfer. J Mol Endocrinol. 2003;31:461–71.

    Article  CAS  PubMed  Google Scholar 

  29. Müller M, Soloff MS, Fahrenholz F. Photoaffinity labelling of the oxytocin receptor in plasma membranes from rat mammary gland. FEBS Lett. 1989;242:333–6.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We appreciate Dr. Tao-Fei Yan (ChangHai hospital, Second Military Medical University, ShangHai, China.) for his recommendation to this study design.

Author information

Authors and Affiliations

  1. Graduate Management Unit, Second Military Medical University, Shanghai, China

    Chao Lui

  2. Department of Urology, 2nd Affiliated Hospital of Second Military Medical University, Shanghai, China

    Xin-gang Cui & Dan-feng Xu

  3. Shanghai Institute of Andrology, Renji Hospital, Shanghai, China

    Yi-xin Wang

  4. Neuroscience Institute, 2nd Affiliated Hospital of Second Military Medical University, Shanghai, China

    Zhen-dong You

Authors
  1. Chao Lui
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xin-gang Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yi-xin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhen-dong You
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dan-feng Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Zhen-dong You or Dan-feng Xu.

Additional information

Capsule

Oxytocin/oxytocin receptor system is linked with male infertility.

Xin-gang Cui is co-first author with Chao Lui.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lui, C., Cui, Xg., Wang, Yx. et al. Association between neuropeptide oxytocin and male infertility. J Assist Reprod Genet 27, 525–531 (2010). https://doi.org/10.1007/s10815-010-9451-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-010-9451-2

Keywords

Search

Navigation