Occurrence and reproductive roles of hormones in seminal plasma

Only 2–5% of seminal fluid is composed of spermatozoa, while the rest is seminal plasma. The seminal plasma is a rich cocktail of organic and inorganic compounds including hormones, serving as a source of nutrients for sperm development and maturation, protecting them from infection and enabling them to overcome the immunological and chemical environment of the female reproductive tract. In this review, a survey of the hormones found in human seminal plasma, with particular emphasis on reproductive hormones is provided. Their participation in fertilization is discussed including their indispensable role in ovum fertilization. The origin of individual hormones found in seminal plasma is discussed, along with differences in the concentrations in seminal plasma and blood plasma. A part of review is devoted to methods of measurement, emphasising particular instances in which they differ from measurement in blood plasma. These methods include separation techniques, overcoming the matrix effect and current ways for end-point measurement, focusing on so called hyphenated techniques as a combination of chromatographic separation and mass spectrometry. Finally, the informative value of their determination as markers of male fertility disorders (impaired spermatogenesis, abnormal sperm parameters, varicocele) is discussed, along with instances where measuring their levels in seminal plasma is preferable to measurement of levels in blood plasma.RésuméLes spermatozoïdes ne représentent que 2 à 25% du liquide séminal, le reste étant constitué par le plasma séminal. Le plasma séminal est un cocktail de composés organiques et non organiques comprenant des hormones qui font office de source de substances nutritives pour le développement et la maturation des spermatozoïdes, qui les protègent de l’infection et leur permettent de surmonter l’environnement immunologique et chimique de l’appareil reproducteur féminin. La présente revue propose une vue d’ensemble des hormones retrouvées dans le plasma séminal de l’homme, l’accent étant particulièrement mis sur les hormones reproductives. La participation de ces dernières au processus de fécondation est discutée, y compris leur rôle indispensable dans la fécondation de l’ovocyte. L’origine de chacune des hormones retrouvées dans le plasma séminal est décrite, ainsi que les différences de leurs concentrations dans le plasma séminal et dans le plasma sanguin. Une partie de cette revue est dévolue aux méthodes de mesure, en soulignant des exemples particuliers où elles diffèrent des mesures dans le plasma sanguin. Ces méthodes comprennent les techniques de séparation, qui surmontent les effets matriciels et les procédures actuelles de critère de mesure, en se concentrant sur les techniques dites de couplage comme la combinaison de la séparation chromatographique et de la spectrométrie de masse. Enfin, la valeur informative de la détermination de ces hormones en tant que marqueurs des anomalies de la fertilité masculine (spermatogenèse altérée, paramètres spermatiques anormaux, varicocèle) est discutée, ainsi que les situations où la mesure de leurs taux dans le plasma séminal est préférable à celle du plasma sanguin.

[1]  E. S. Díaz,et al.  Participation of protein kinases and phosphatases in the progesterone‐induced acrosome reaction and calcium influx in human spermatozoa , 2016, Andrology.

[2]  J. Guéchot,et al.  Seminal androgen concentrations and residual sperm cytoplasm. , 1998, Clinica chimica acta; international journal of clinical chemistry.

[3]  R. Kučera,et al.  Anti-Müllerian hormone in serum and seminal plasma in comparison with other male fertility parameters , 2016, Systems biology in reproductive medicine.

[4]  P. Herer,et al.  Seminal plasma androgen/oestrogen balance in infertile men. , 2002, International journal of andrology.

[5]  M. Hill,et al.  Associations of bisphenol A and polychlorinated biphenyls with spermatogenesis and steroidogenesis in two biological fluids from men attending an infertility clinic. , 2016, Environment international.

[6]  Sarman Singh,et al.  N-Glycoproteomics of Human Seminal Plasma Glycoproteins. , 2016, Journal of proteome research.

[7]  C. Letizia,et al.  The level of adrenomedullin immunoreactivity in seminal fluid is higher in oligozoospermic subjects and correlates with semen biochemical parameters. , 2007, European journal of obstetrics, gynecology, and reproductive biology.

[8]  S. D. du Plessis,et al.  The in vitro effects of melatonin on human sperm function and its scavenging activities on NO and ROS , 2010, Andrologia.

[9]  Fátima Regina Mena Barreto Silva,et al.  Interactions between oestrogen and 1α,25(OH)2-vitamin D3 signalling and their roles in spermatogenesis and spermatozoa functions , 2017, Basic and Clinical Andrology.

[10]  J. Rigot,et al.  Seminal plasma levels of anti-Müllerian hormone and inhibin B are not predictive of testicular sperm retrieval in nonobstructive azoospermia: a study of 139 men. , 2010, Fertility and sterility.

[11]  M. Isola,et al.  Oxytocin immunoreactivity in the human urethral (Littrè's) glands. , 2010, The Journal of reproduction and development.

[12]  J. Malm,et al.  Semenogelin I and II, the predominant human seminal plasma proteins, are also expressed in non-genital tissues. , 2002, Molecular human reproduction.

[13]  R. Hampl,et al.  Determination of seven selected neuro- and immunomodulatory steroids in human cerebrospinal fluid and plasma using LC-MS/MS , 2015, Steroids.

[14]  B. Gertz,et al.  MK-386, an inhibitor of 5alpha-reductase type 1, reduces dihydrotestosterone concentrations in serum and sebum without affecting dihydrotestosterone concentrations in semen. , 1997, The Journal of clinical endocrinology and metabolism.

[15]  A. J. Yun,et al.  Sympathetic and T helper (Th)2 bias may ameliorate uterine fibroids, independent of sex steroids. , 2005, Medical hypotheses.

[16]  S. Ratnam,et al.  Concentrations of intracellular sex steroids in human spermatozoa. , 1993, Archives of andrology.

[17]  E. Diamandis,et al.  Seminal plasma as a diagnostic fluid for male reproductive system disorders , 2014, Nature Reviews Urology.

[18]  Jean D. Wilson The critical role of androgens in prostate development. , 2011, Endocrinology and metabolism clinics of North America.

[19]  N. Cross Human seminal plasma prevents sperm from becoming acrosomally responsive to the agonist, progesterone: cholesterol is the major inhibitor. , 1996, Biology of reproduction.

[20]  E. Baldi,et al.  Human spermatozoa as a model for studying membrane receptors mediating rapid nongenomic effects of progesterone and estrogens , 2004, Steroids.

[21]  Bin Wang,et al.  Rapid and sensitive analysis of phthalate metabolites, bisphenol A, and endogenous steroid hormones in human urine by mixed-mode solid-phase extraction, dansylation, and ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry , 2013, Analytical and Bioanalytical Chemistry.

[22]  M. Fraczek,et al.  Cytokines in the male reproductive tract and their role in infertility disorders. , 2015, Journal of reproductive immunology.

[23]  G. Bolelli,et al.  Seminal estrone, estrone sulfate, and estradiol-17 beta levels in fertile and infertile males. , 1991, Archives of andrology.

[24]  I. Blair,et al.  Ultra-high sensitivity analysis of estrogens for special populations in serum and plasma by liquid chromatography–mass spectrometry: Assay considerations and suggested practices , 2016, The Journal of Steroid Biochemistry and Molecular Biology.

[25]  J. Brotherton Vasopressin: another pregnancy protein in human seminal plasma , 2009, Andrologia.

[26]  R. Hampl,et al.  Hormones and endocrine disruptors in human seminal plasma. , 2013, Endocrine regulations.

[27]  B. Robaire,et al.  Androgen action in the epididymis. , 2011, Journal of andrology.

[28]  C. Niederberger,et al.  Hormonal evaluation of the infertile male: has it evolved? , 2008, The Urologic clinics of North America.

[29]  M. Fujisawa,et al.  The significance of anti-Müllerian hormone concentration in seminal plasma for spermatogenesis. , 2002, Human reproduction.

[30]  V. Nacharaju,et al.  Presence of 11β-hydroxysteroid dehydrogenase in human semen: Evidence of correlation with semen characteristics , 1997, Steroids.

[31]  J. Brotherton Cortisol and transcortin in human seminal plasma and amniotic fluid as estimated by modern specific assays , 2009, Andrologia.

[32]  Ping Liu,et al.  Assessment of seminal estradiol and testosterone levels as predictors of human spermatogenesis. , 2010, Journal of andrology.

[33]  Organización Mundial de la Salud WHO laboratory manual for the examination and processing of human semen , 2010 .

[34]  G. Swyer,et al.  Determinantion of testosterone concentration in semen of men with normal or subnormal sperm counts and after vasectomy. , 1976, Acta Europaea fertilitatis.

[35]  Y. Siow,et al.  The presence of müllerian inhibiting substance in human seminal plasma. , 1996, Human reproduction.

[36]  Louis W. Chang,et al.  Quantitative measurement of male steroid hormones using automated on-line solid phase extraction-liquid chromatography-tandem mass spectrometry and comparison with radioimmunoassay. , 2003, The Analyst.

[37]  D. French Advances in bioanalytical techniques to measure steroid hormones in serum. , 2016, Bioanalysis.

[38]  Lucie Nováková,et al.  Challenges in the development of bioanalytical liquid chromatography-mass spectrometry method with emphasis on fast analysis. , 2013, Journal of chromatography. A.

[39]  Y. Kumamoto,et al.  Human Chorionic Gonadotropin β-Subunit in Human Semen , 1988 .

[40]  M. Hill,et al.  Development and validation of LC-MS/MS method for quantification of bisphenol A and estrogens in human plasma and seminal fluid. , 2015, Talanta.

[41]  P. Taylor Matrix effects: the Achilles heel of quantitative high-performance liquid chromatography-electrospray-tandem mass spectrometry. , 2005, Clinical biochemistry.

[42]  S. Loche,et al.  Seminal fluid androgen levels in infertile patients. , 1987, International journal of fertility.

[43]  F. Comhaire,et al.  Androgens in seminal plasma: markers of the surface epithelium of the male reproductive tract. , 1995, International journal of andrology.

[44]  L. Giordani,et al.  Clinical, endocrine, and molecular findings in 17β -hydroxysteroid dehydrogenase type 3 deficiency , 2008, Journal of endocrinological investigation.

[45]  J. Imperato-McGinley,et al.  Androgens and male physiology the syndrome of 5α-reductase-2 deficiency , 2002, Molecular and Cellular Endocrinology.

[46]  H. Lilja,et al.  Seminal vesicle-secreted proteins and their reactions during gelation and liquefaction of human semen. , 1987, The Journal of clinical investigation.

[47]  C. Shah,et al.  Non-genomic membrane progesterone receptors on human spermatozoa. , 2007, Society of Reproduction and Fertility supplement.

[48]  S. Dissing,et al.  Non-genomic effects of vitamin D in human spermatozoa , 2012, Steroids.

[49]  Martin Blomberg Jensen,et al.  Vitamin D and male reproduction , 2014, Nature Reviews Endocrinology.

[50]  C. Pauerstein,et al.  Peptide and steroid hormone concentrations in human seminal plasma. , 1984, International journal of fertility.

[51]  T. Mostafa,et al.  Seminal plasma oxytocin and oxidative stress levels in infertile men with varicocele , 2015, Andrologia.

[52]  A. Lübbert,et al.  Parathyroid hormone: another pregnancy protein present in human seminal plasma and amniotic fluid , 2009, Andrologia.

[53]  E. Diamandis,et al.  Differential Diagnosis of Azoospermia with Proteomic Biomarkers ECM1 and TEX101 Quantified in Seminal Plasma , 2013, Science Translational Medicine.

[54]  Li Chen,et al.  Relationship between Lipids Levels of Serum and Seminal Plasma and Semen Parameters in 631 Chinese Subfertile Men , 2016, PloS one.

[55]  J. Miners,et al.  The Novel UDP Glycosyltransferase 3A2: Cloning, Catalytic Properties, and Tissue Distribution , 2011, Molecular Pharmacology.

[56]  R. Scholler,et al.  Estrogens in seminal plasma of human and animal species: identification and quantitative estimation by gas chromatography-mass spectrometry associated with stable isotope dilution. , 1982, Journal of steroid biochemistry.

[57]  P. Herer,et al.  SEMINAL PLASMA MELATONIN AND GONADAL STEROIDS CONCENTRATIONS IN NORMAL MEN , 2002, Archives of andrology.

[58]  Patrick Y Lee,et al.  Immunomodulatory function of seminal catecholamines may be an adaptation for reproduction. , 2004, Medical hypotheses.

[59]  A. Khalifa,et al.  Concentration of Calcitonin in Seminal Plasma of Infertile Men/Calcitonin‐Konzentration im Spermaplasma von unfruchtbaren Männern , 2009, Andrologia.

[60]  D. Sibley,et al.  The Blood-Testis Barrier and Its Implications for Male Contraception , 2012, Pharmacological Reviews.

[61]  C. Pineau,et al.  Identification of genital tract markers in the human seminal plasma using an integrative genomics approach. , 2013, Human reproduction.

[62]  A. Toro,et al.  Physiological action of oestradiol on the acrosome reaction in human spermatozoa , 2008, Andrologia.

[63]  E. Battaner,et al.  Hormone levels in serum and seminal plasma of men with different types of azoospermia. , 1983, Journal of reproduction and fertility.

[64]  A. Agarwal,et al.  Thyroid, spermatogenesis, and male infertility. , 2011, Frontiers in bioscience.

[65]  T. Thalhammer,et al.  Decreased melatonin levels and increased levels of advanced oxidation protein products in the seminal plasma are related to male infertility. , 2016, Reproduction, fertility, and development.

[66]  R. Hampl,et al.  Differences in bisphenol A and estrogen levels in the plasma and seminal plasma of men with different degrees of infertility. , 2015, Physiological research.

[67]  T. Higashi,et al.  Chemical derivatization for enhancing sensitivity during LC/ESI–MS/MS quantification of steroids in biological samples: a review , 2016, The Journal of Steroid Biochemistry and Molecular Biology.

[68]  B. Keevil,et al.  Supported liquid extraction as an alternative to solid phase extraction for LC-MS/MS aldosterone analysis? , 2013, Annals of clinical biochemistry.

[69]  A. Rocha,et al.  Seminal plasma concentrations of Anti‐Müllerian hormone and inhibin B predict motile sperm recovery from cryopreserved semen in asthenozoospermic men: a prospective cohort study , 2014, Andrology.

[70]  J. Petersen,et al.  Cross-reactivity of steroid hormone immunoassays : clinical significance and two-dimensional molecular similarity prediction , 2014 .

[71]  I. Wilson,et al.  Hyphenation and hypernation the practice and prospects of multiple hyphenation. , 2003, Journal of chromatography. A.

[72]  W. Luqman,et al.  Prolactin in seminal fluid. , 1982, Archives of andrology.

[73]  T. Higashi,et al.  Alternative procedure for charged derivatization to enhance detection responses of steroids in electrospray ionization-MS. , 2007, Chemical & pharmaceutical bulletin.

[74]  S. Sauvé,et al.  Analysis of steroid hormones and their conjugated forms in water and urine by on-line solid-phase extraction coupled to liquid chromatography tandem mass spectrometry , 2016, Chemistry Central Journal.

[75]  P. Leung,et al.  The renin-angiotensin system and male reproduction: new functions for old hormones. , 2003, Journal of molecular endocrinology.

[76]  R. Brezinschek,et al.  Cytokine levels in the seminal plasma of infertile males. , 1996, Journal of andrology.

[77]  I. Bejarano,et al.  High endogenous melatonin concentrations enhance sperm quality and short‐term in vitro exposure to melatonin improves aspects of sperm motility , 2010, Journal of pineal research.

[78]  H. Sjöberg,et al.  High concentration of immunoreactive calcitonin of prostatic origin in human semen. , 1980, Acta physiologica Scandinavica.

[79]  John L Blau,et al.  Cross-reactivity of steroid hormone immunoassays: clinical significance and two-dimensional molecular similarity prediction , 2014, BMC Clinical Pathology.

[80]  E. Kratz,et al.  Lower expression of the α2,3-sialylated fibronectin glycoform and appearance of the asialo-fibronectin glycoform are associated with high concentrations of fibronectin in human seminal plasma with abnormal semen parameters , 2006, Clinical chemistry and laboratory medicine.

[81]  M. Sawyer,et al.  Liquid chromatography tandem mass spectrometry determination of free and conjugated estrogens in breast cancer patients before and after exemestane treatment. , 2014, Analytica chimica acta.

[82]  H. Nicholson,et al.  Oxytocin--its role in male reproduction and new potential therapeutic uses. , 2006, Human reproduction update.

[83]  E. Kratz,et al.  Fucose and Sialic Acid Expressions in Human Seminal Fibronectin and α1-Acid Glycoprotein Associated with Leukocytospermia of Infertile Men , 2011, Disease markers.

[84]  A. Wetzels,et al.  A neuropeptide in human semen: oxytocin. , 1998, Archives of andrology.

[85]  A. Zarate,et al.  Abnormal prolactin levels in serum and seminal plasma in infertile men. , 1980, Archives of andrology.

[86]  R. Ramasamy,et al.  The role of estradiol in male reproductive function , 2016, Asian journal of andrology.

[87]  L. Deftos,et al.  Presence of calcitonin‐like immunoreactivity (iCT) in human prostate gland: Evidence for iCT secretion by cultured prostate cells , 1992, The Prostate.

[88]  R. Baxendale,et al.  Regulation of mammalian sperm capacitation by endogenous molecules. , 2006, Frontiers in bioscience : a journal and virtual library.

[89]  M. Hill,et al.  Gas chromatographic–mass spectrometric identification of 16α-hydroxy-dehydroepiandrosterone in human seminal plasma , 2004, Steroids.

[90]  J. Imperato-McGinley,et al.  Androgens and male physiology the syndrome of 5alpha-reductase-2 deficiency. , 2002, Molecular and cellular endocrinology.

[91]  F. Labrie,et al.  Expression of sulfotransferase 1E1 in human prostate as studied by in situ hybridization and immunocytochemistry , 2007, The Prostate.

[92]  J. Tamm,et al.  Unconjugated 5α‐Androstan‐3α, 17β‐Diol and 5α‐Androstane‐3β, 17β‐Diol in Normal and Pathological Human Seminal Plasma. Comparison with Testosterone, 5α‐Dihydrotestosterone and Testosterone‐Glucosiduronate * , 2009 .

[93]  H. Atta,et al.  Melatonin hormone profile in infertile males. , 2006, International journal of andrology.

[94]  C. Cheng,et al.  The Mammalian Blood-Testis Barrier: Its Biology and Regulation. , 2015, Endocrine reviews.

[95]  R. Hampl,et al.  Steroids in semen, their role in spermatogenesis, and the possible impact of endocrine disruptors , 2013, Hormone molecular biology and clinical investigation.

[96]  M. Hill,et al.  The content of four immunomodulatory steroids and major androgens in human semen , 2003, The Journal of Steroid Biochemistry and Molecular Biology.

[97]  C. Niederberger,et al.  Human chorionic gonadotropin free beta-subunit in the human seminal plasma: a new marker for spermatogenesis? , 2003, European journal of obstetrics, gynecology, and reproductive biology.

[98]  G. Krassas,et al.  Male reproductive function in relation with thyroid alterations. , 2004, Best practice & research. Clinical endocrinology & metabolism.

[99]  R. Lobo,et al.  Presence of immunoreactive beta-endorphin and calcitonin in human seminal plasma, and their relation to sperm physiology. , 1989, Fertility and sterility.

[100]  M. El-Mogy,et al.  Seminal androgens, oestradiol and progesterone in oligoasthenoteratozoospermic men with varicocele , 2014, Andrologia.

[101]  A. Colao,et al.  The role of vitamin D in male fertility: A focus on the testis , 2017, Reviews in Endocrine and Metabolic Disorders.

[102]  P. Vigil,et al.  Assessment of the effect of testosterone on the acrosome reaction of human spermatozoa , 2012, Andrologia.

[103]  M. Ben-david,et al.  Prolactin in seminal plasma of infertile men. , 1978, Archives of andrology.

[104]  J. Tostain,et al.  Significance of inhibin B and anti-Müllerian hormone in seminal plasma: a preliminary study. , 2008, Fertility and sterility.

[105]  A. Atan,et al.  EFFECT OF SEMINAL PLASMA CALCITONIN LEVELS ON SPERM MOTILITY , 2001, Archives of andrology.

[106]  G. Pelletier Expression of steroidogenic enzymes and sex-steroid receptors in human prostate. , 2008, Best practice & research. Clinical endocrinology & metabolism.

[107]  C. Sultan,et al.  Increased oestradiol level in seminal plasma in infertile men. , 1993, Human reproduction.

[108]  W. Griffiths,et al.  General Methods for the Extraction, Purification, and Measurement of Steroids by Chromatography and Mass Spectrometry , 2010 .

[109]  W. Yuan,et al.  The Association Between Calcium, Magnesium, and Ratio of Calcium/Magnesium in Seminal Plasma and Sperm Quality , 2016, Biological Trace Element Research.

[110]  Ľ. Stárka,et al.  Changes in the Concentrations of Corticoid Metabolites--The Effect of Stress, Diet and Analytical Method. , 2015, Prague medical report.

[111]  Y. Siow,et al.  Andrology: The presence of Müllerian inhibiting substance in human seminal plasma , 1996 .

[112]  L. Yogev,et al.  High levels of catecholamines in human semen: a preliminary study , 2001, Andrologia.

[113]  J. Burka,et al.  Isolation of leukotriene C4 from human seminal fluid. , 1983, Prostaglandins.

[114]  K. Roberts Sterol sulfates in the epididymis; synthesis and possible function in the reproductive process. , 1987, Journal of steroid biochemistry.

[115]  Mingyao Liu,et al.  New insights into the androgen biotransformation in prostate cancer: A regulatory network among androgen, androgen receptors and UGTs. , 2016, Pharmacological research.

[116]  C. Foresta,et al.  Calcitonin in Human Seminal Plasma and its Localization on Human Spermatozoa , 2009, Andrologia.

[117]  S. Christin-Maitre,et al.  Dosages hormonaux chez l’homme infertile , 2008 .

[118]  D. Allalouf,et al.  β-Endorphin and Calcitonin in Human Semen , 1989 .

[119]  M. Negishi,et al.  Cellular localization and regulation of expression of testicular estrogen sulfotransferase. , 1997, Endocrinology.

[120]  S. Karras,et al.  Vitamin D in human reproduction: a narrative review , 2013, International journal of clinical practice.

[121]  C. Gagnon,et al.  Semenogelin I: a coagulum forming, multifunctional seminal vesicle protein , 1999, Cellular and Molecular Life Sciences CMLS.

[122]  H. Rosing,et al.  Stable isotopically labeled internal standards in quantitative bioanalysis using liquid chromatography/mass spectrometry: necessity or not? , 2005, Rapid communications in mass spectrometry : RCM.

[123]  G. Bellastella,et al.  Seminal anti-Müllerian hormone level is a marker of spermatogenic response during long-term gonadotropin therapy in male hypogonadotropic hypogonadism. , 2008, Human reproduction.

[124]  F. Caprio,et al.  Seminal anti‐Müllerian hormone levels during recombinant human follicle‐stimulating hormone treatment in men with idiopathic infertility undergoing assisted reproduction cycles , 2015, Andrology.

[125]  R. Rey,et al.  Anti-Müllerian hormone as a seminal marker for spermatogenesis in non-obstructive azoospermia. , 1999, Human reproduction.

[126]  M. Amer,et al.  Seminal plasma anti-Müllerian hormone level correlates with semen parameters but does not predict success of testicular sperm extraction (TESE). , 2007, Asian journal of andrology.