Pharmacogenetics of FSH action in the Male

Frontiers in Endocrinology

Volumn 10, Issue , 2019, Pages

  Schubert, Maria ^a   Lanuza, Lina Pérez ^a   Gromoll, Jörg ^a  

^a UNIVERSITY HOSPITAL MÜNSTER   (Germany)

Author keywords

FSH; Genetics; Idiopathic male infertility; Pharmacogenetic studies; Single nucleotide polymorphism (SNP); Spermatogenesis

Indexed keywords

CHORIONIC GONADOTROPIN; FOLLITROPIN; FOLLITROPIN RECEPTOR; FORKHEAD BOX PROTEIN L2; GLIAL CELL LINE DERIVED NEUROTROPHIC FACTOR; GONADORELIN; LUTEINIZING HORMONE; NUCLEAR RECEPTOR NUR77; RECOMBINANT FOLLITROPIN; SMAD PROTEIN; STROMAL CELL DERIVED FACTOR 1; TESTOSTERONE; THYROTROPIN; TRANSCRIPTION FACTOR LHX3;

ALLELE; APOPTOSIS; ARTICLE; CELL PROLIFERATION; DOWN REGULATION; ENDOCRINE FUNCTION; GENE; GENE EXPRESSION; GENE FREQUENCY; GENE MUTATION; GENOTYPE; HORMONE ACTION; HUMAN; MALE; MALE GENITAL TRACT PARAMETERS; MALE INFERTILITY; OUTCOME ASSESSMENT; PHARMACOGENETICS; PREGNANCY RATE; PROTEIN EXPRESSION; PUBERTY; SEMEN ANALYSIS; SERTOLI CELL; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM; SPERMATOGENESIS; SPERMATOZOON COUNT; SPERMATOZOON MOTILITY; SYSTEMATIC REVIEW; TREATMENT RESPONSE; UPREGULATION;

EID: 85065466308     PISSN: None     EISSN: 16642392     Source Type: Journal    
DOI: 10.3389/fendo.2019.00047     Document Type: Article

References (76)

1. Jungwirth A, Diemer T, Dohle GR, Giwercman A, Kopa Z, Krausz C, et al. Guidelines on male infertility. In: European Association of Urology (2015). p. 1–42. Available online at: https://uroweb.org/wp-content/uploads/17-MaleInfertility_LR1.pdf
2. Tüttelmann F, Ruckert C, Röpke A. Disorders of spermatogenesis: perspectives for novel genetic diagnostics after 20 years of unchanged routine. Med Genet. (2018) 30:12–20. doi: 10.1007/s11825-018-0181-7
3. Busch AS, Kliesch S, Tüttelmann F, Gromoll J. FSHB−211G>T stratification for follicle-stimulating hormone treatment of male infertility patients: making the case for a pharmacogenetic approach in genetic functional secondary hypogonadism. Andrology. (2015) 3:1050–3. doi: 10.1111/andr. 12094
4. Dunnen JT, Dalgleish R, Maglott DR, Hart RK, Greenblatt MS, McGowan-Jordan J, et al. HGVS Recommendations for the description of sequence variants: 2016 update. Hum Mutat. (2016) 37:564–9. doi: 10.1002/humu. 22981
5. Ross S, Anand SS, Joseph P, Paré G. Promises and challenges of pharmacogenetics: an overview of study design, methodological and statistical issues. JRSM Cardiovasc Dis. (2012) 1:1–13. doi: 10.1258/cvd.2012. 012001
6. Huhtaniemi I. Hormonal regulation of spermatogenesis: mutant mice challenging old paradigms. Eur J Endocrinol. (2018) 179:R143–50. doi: 10.1530/EJE-18-0396
7. Attia AM, Abou-Setta AM, Al-Inany HG. Gonadotrophins for idiopathic male factor subfertility. Cochrane Database Syst Rev. (2013) 2013:CD005071. doi: 10.1002/14651858.CD005071.pub4
8. Santi D, Potì F, Simoni M, Casarini L. Pharmacogenetics of G-protein-coupled receptors variants: FSH receptor and infertility treatment. Best Pract Res Clin Endocrinol Metab. (2018) 32:189–200. doi: 10.1016/j.beem.2018. 01.001
9. Colpi GM, Francavilla S, Haidl G, Link K, Behre HM, Goulis DG, et al. European academy of andrology guideline management of oligo-astheno-teratozoospermia. Andrology. (2018) 6:513–24. doi: 10.1111/andr.12502
10. Barbonetti A, Calogero AE, Balercia G, Garolla A, Krausz C, La Vignera S, et al. The use of follicle stimulating hormone (FSH) for the treatment of the infertile man: position statement from the Italian Society of Andrology and Sexual Medicine (SIAMS). J Endocrinol Invest. (2018) 41:1107–22. doi: 10.1007/s40618-018-0843-y
11. Blumenauer V, Czeromin U, Fiedler K, Gnoth C, Happel L, Krüssel JS, et al. D.I.R. Annual 2014 - The German IVF-Registry. J Reproduktionsmed Endokinol. (2015) 12:509–45.
12. Esteves SC, Roque M, Bedoschi G, Haahr T, Humaidan P. Intracytoplasmic sperm injection for male infertility and consequences for offspring. Nat Rev Urol. (2018) 15:535–62. doi: 10.1038/s41585-018-0051-8
13. Siegel ET, Kim HG, Nishimoto HK, Layman LC. The molecular basis of impaired follicle-stimulating hormone action: evidence from human mutations and mouse models. Reprod Sci. (2013) 20:211–33. doi: 10.1177/1933719112461184
14. Bernard DJ, Fortin J, Wang Y, Lamba P. Mechanisms of FSH synthesis: what we know, what we don’t, and why you should care. Fertil Steril. (2010) 93:2465–85. doi: 10.1016/j.fertnstert.2010.03.034
15. Tarulli GA, Stanton PG, Loveland KL, Rajpert-De Meyts E, McLachlan RI, Meachem SJ. A survey of Sertoli cell differentiation in men after gonadotropin suppression and in testicular cancer. Spermatogenesis. (2013) 3:e24014–e24014. doi: 10.4161/spmg.24014
16. França LR, Hess RA, Dufour JM, Hofmann MC, Griswold MD. The Sertoli cell: one hundred fifty years of beauty and plasticity. Andrology. (2016) 4:189–212. doi: 10.1111/andr.12165
17. Alves MG, Rato L, Carvalho RA, Moreira PI, Socorro S, Oliveira PF. Hormonal control of Sertoli cell metabolism regulates spermatogenesis. Cell Mol Life Sci. (2013) 70:777–93. doi: 10.1007/s00018-012-1079-1
18. Busch AS, Hagen CP, Main KM, Pereira A, Corvalan C, Almstrup K, et al. Genetic variation of follicle-stimulating hormone action is associated with age at testicular growth in boys. J Clin Endocrinol Metab. (2017) 102:1740–9. doi: 10.1210/jc.2016-4013
19. Shiraishi K, Matsuyama H. Gonadotoropin actions on spermatogenesis and hormonal therapies for spermatogenic disorders. Endocr J. (2017) 64:123–31. doi: 10.1507/endocrj.EJ17-0001
20. Schlatt S, Ehmcke J. Regulation of spermatogenesis: an evolutionary biologist’s perspective. Semin Cell Dev Biol. (2014) 29:2–16. doi: 10.1016/j.semcdb.2014.03.007
21. Ding LJ, Yan GJ, Ge QY, Yu F, Zhao X, Diao ZY, et al. FSH acts on the proliferation of type a spermatogonia via Nur77 that increases GDNF expression in the Sertoli cells. FEBS Lett. (2011) 585:2437–44. doi: 10.1016/j.febslet.2011.06.013
22. Tadokoro Y, Yomogida K, Ohta H, Tohda A, Nishimune Y. Homeostatic regulation of germinal stem cell proliferation by the GDNF/FSH pathway. Mech Dev. (2002) 113:29–39. doi: 10.1016/S0925-4773(02)00004-7
23. Gloaguen P, Crépieux P, Heitzler D, Poupon A, Reiter E. Mapping the follicle-stimulating hormone-induced signaling networks. Front Endocrinol. (2011) 2:45. doi: 10.3389/fendo.2011.00045
24. Jiang X, Liu H, Chen X, Chen P-H, Fischer D, Sriraman V, et al. Structure of follicle-stimulating hormone in complex with the entire ectodomain of its receptor. Proc Natl Acad Sci USA. (2012) 109:12491–6. doi: 10.1073/pnas.1206643109
25. Huhtaniemi I, Toppari J. FSH Regulation at the molecular and cellular levels: mechanisms of action and functional effects. Sertoli Cell Biol. (2005) 155–69. doi: 10.1016/B978-012647751-1/50011-8
26. Walker WH, Cheng J. FSH and testosterone signaling in sertoli cells. Reproduction. (2005) 130:15–28. doi: 10.1530/rep.1.00358
27. Zimmermann C, Stévant I, Borel C, Conne B, Pitetti J-L, Calvel P, et al. Research resource: the dynamic transcriptional profile of sertoli cells during the progression of spermatogenesis. Mol Endocrinol. (2015) 29:627–42. doi: 10.1210/me.2014-1356
28. Thackray VG. Fox tales: regulation of gonadotropin gene expression by forkhead transcription factors. Mol Cell Endocrinol. (2014) 385:62–70. doi: 10.1016/j.mce.2013.09.034
29. Rasmussen SGF, DeVree BT, Zou Y, Kruse AC, Chung KY, Kobilka TS, et al. Crystal structure of the β2 adrenergic receptor-Gs protein complex. Nature. (2011) 477:549–55. doi: 10.1038/nature10361
30. Laan M, Europe PMC Funders Group. Pharmacogenetics of FSH Action. Curr Opin Endocrinol Diabetes Obes. (2012) 19:220–227. doi: 10.1097/MED.0b013e3283534b11
31. Zheng J, Mao J, Cui M, Liu Z, Wang X, Xiong S, et al. Novel FSHβ mutation in a male patient with isolated FSH deficiency and infertility. Eur J Med Genet. (2017) 60:335–9. doi: 10.1016/j.ejmg.2017.04.004
32. Consortium T 1000 GP, Auton A, Abecasis GR, Altshuler DM, Durbin RM, Abecasis GR, et al. A global reference for human genetic variation. Nature. (2015) 526:68. doi: 10.1038/nature15393
33. Benson CA, Kurz TL, Thackray VG. A human FSHB promoter SNP associated with low FSH levels in men impairs LHX3 binding and basal FSHB transcription. Endocrinology. (2013) 154:3016–21. doi: 10.1210/en.2013-1294
34. Simoni M, Gromoll J, Nieschlag E. The follicle-stimulating hormone receptor: biochemistry, molecular biology, physiology and pathophysiology. Endocr Rev. (1997) 18:739–73.
35. Gromoll J, Simoni M. Genetic complexity of FSH receptor function. Trends Endocrinol Metab. (2005) 16:368–73. doi: 10.1016/j.tem.2005.05.011
36. George JW, Dille EA, Heckert LL. Current concepts of follicle-stimulating hormone receptor gene regulation1. Biol Reprod. (2011) 84:7–17. doi: 10.1095/biolreprod.110.085043
37. Simoni M, Gromoll J, Höppner W, Kamischke A, Krafft T, Stähle D, et al. Mutational analysis of the follicle-stimulating hormone (FSH) receptor in normal and infertile men: identification and characterization of two discrete FSH receptor isoforms1. J Clin Endocrinol Metab. (1999) 84:751–5. doi: 10.1210/jcem.84.2.5500
38. Simoni M, Casarini L. Mechanisms in endocrinology: geneticsof FSH action - A 2014-and-beyond view. Eur J Endocrinol. (2014) 170:91–107. doi: 10.1530/EJE-13-0624
39. Wunsch A, Ahda Y, Banaz-Yaşar F, Sonntag B, Nieschlag E, Simoni M, et al. Single-nucleotide polymorphisms in the promoter region influence the expression of the human follicle-stimulating hormone receptor. Fertil Steril. (2005) 84:446–53. doi: 10.1016/j.fertnstert.2005.02.031
40. Strothmann K, Simoni M, Mathur P, Siakhamary S, Nieschlag E, Gromoll J. Gene expression profiling of mouse sertoli cell lines. Cell Tissue Res. (2004) 315:249–57. doi: 10.1007/s00441-003-0834-x
41. Wang H, Wen L, Yuan Q, Sun M, Niu M, He Z. Establishment and applications of male germ cell and Sertoli cell lines. Reproduction. (2016) 152:R31–40. doi: 10.1530/REP-15-0546
42. Griswold MD, Kim J-S. Site-specific methylation of the promoter alters deoxyribonucleic acid-protein interactions and prevents follicle-stimulating hormone receptor gene transcription1. Biol Reprod. (2001) 64:602–10. doi: 10.1095/biolreprod64.2.602
43. ′ -untranslated region associated with female hypertension. Hypertension. (2006) 48:512–8. doi: 10.1161/01.HYP.0000233877.84343.d7
44. Alviggi C, Conforti A, Santi D, Esteves SC, Andersen CY, Humaidan P, et al. Clinical relevance of genetic variants of gonadotrophins and their receptors in controlled ovarian stimulation: a systematic review and meta-analysis. Hum Reprod Update. (2018) 24:599–614. doi: 10.1093/humupd/ dmy019
45. Alviggi C, Conforti A, Caprio F, Gizzo S, Noventa M, Strina I, et al. In estimated good prognosis patients could unexpected “Hyporesponse” to controlled ovarian stimulation be related to genetic polymorphisms of FSH receptor? Reprod Sci. (2016) 23:1103–8. doi: 10.1177/1933719116 630419
46. ∗. J Clin Endocrinol Metab. (2000) 85:3365–9. doi: 10.1210/jcem.85.9.6789
47. Nordhoff V, Sonntag B, von Tils D, Götte M, Schüring AN, Gromoll J, et al. Effects of the FSH receptor gene polymorphism p.N680S on cAMP and steroid production in cultured primary human granulosa cells. Reprod Biomed Online. (2011) 23:196–203. doi: 10.1016/j.rbmo.2011.04.009
48. Gromoll J, Bröcker M, Derwahl M, Höppner W. Detection of mutations in glycoprotein hormone receptors. Methods. (2000) 21:83–97 doi: 10.1006/meth.2000.0977
49. Simoni M, Nieschlag E, Gromoll J. Isoforms and single nucleotide polymorphism of the FSH receptor gene: Implications for human reproduction. Hum Reprod Update. (2002) 8:413–21. doi: 10.1093/humupd/8.5.413
50. Kuechler A, Hauffa BP, Köninger A, Kleinau G, Albrecht B, Horsthemke B, et al. An unbalanced translocation unmasks a recessive mutation in the follicle-stimulating hormone receptor (FSHR) gene and causes FSH resistance. Eur J Hum Genet. (2010) 18:656–61. doi: 10.1038/ejhg. 2009.244
51. Aittomäki K, Dieguez Lucena J, Pakarinen P, Sistonen P, Tapanainen J, Gromoll J, et al. Mutation in the follicle-stimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure. Cell. (1995) 82:959–68 doi: 10.1016/0092-8674(95)90275-9
52. Gromoll J, Simoni M, Nieschlag E. An activating mutation of the follicle-stimulating hormone receptor autonomously sustains spermatogenesis in a hypophysectomized man. J Clin Endocrinol Metab. (1996) 81:1367–70. doi: 10.1210/jcem.81.4.8636335
53. Desai SS, Roy BS, Mahale SD. Mutations and polymorphisms in FSH receptor: functional implications in human reproduction. Reproduction. (2013) 146:R235–48. doi: 10.1530/REP-13-0351
54. Ferlin A, Vinanzi C, Selice R, Garolla A, Frigo AC, Foresta C. Toward a pharmacogenetic approach to male infertility: polymorphism of follicle-stimulating hormone beta-subunit promoter. Fertil Steril. (2011) 96:1344–1349.e2. doi: 10.1016/j.fertnstert.2011.09.034
55. Grigorova M, Punab M, Zilaitiene B, Erenpreiss J, Ausmees K, Matuleviĉius V, et al. Genetically determined dosage of follicle-stimulating hormone (FSH) affects male reproductive parameters. J Clin Endocrinol Metab. (2011) 96:E1534–41. doi: 10.1210/jc.2011-0632
56. Tüttelmann F, Laan M, Grigorova M, Punab M, Sõber S, Gromoll J. Combined effects of the variants FSHB−211G>T and FSHR 2039A>G on male reproductive parameters. J Clin Endocrinol Metab. (2012) 97:3639–47. doi: 10.1210/jc.2012-1761
57. Tamburino L, La Vignera S, Tomaselli V, Condorelli RA, Mongioì LM, Calogero AE. Impact of the FSHB gene−211G/T polymorphism on male gonadal function. J Assist Reprod Genet. (2017) 34:671–6. doi: 10.1007/s10815-017-0896-4
58. Grigorova M, Punab M, Punab AM, Poolamets O, Vihljajev V, Žilaitiene B, et al. Reproductive physiology in young men is cumulatively affected by FSH-action modulating genetic variants: FSHR−29G/A and c.2039 A/G, FSHB−211G/T. PLoS ONE. (2014) 9:e94244. doi: 10.1371/journal.pone.0094244
59. Tamburino L, La Vignera S, Tomaselli V, Condorelli RA, Cannarella R, Mongioì LM, et al. The −29G/A FSH receptor gene polymorphism is associated with higher FSH and LH levels in normozoospermic men. J Assist Reprod Genet. (2017) 34:1289–94. doi: 10.1007/s10815-017-0970-y
60. Wu Q, Zhang J, Zhu P, Jiang W, Liu S, Ni M, et al. The susceptibility of FSHB−211G > T and FSHR G-29A, 919A > G, 2039A > G polymorphisms to men infertility: An association study and meta-analysis. BMC Med Genet. (2017) 18:1–15. doi: 10.1186/s12881-017-0441-4
61. Santi D, Granata AR, Simoni M. Follicle-stimulating hormone treatment of male idiopathic infertility improves pregnancy rate: a meta-analysis. Endocr Connect. (2015) 4: R46–58. doi: 10.1530/EC-15-0050
62. Casamonti E, Vinci S, Serra E, Fino MG, Brilli S, Lotti F, et al. Short-term FSH treatment and sperm maturation: a prospective study in idiopathic infertile men. Andrology. (2017) 5:414–22. doi: 10.1111/andr. 12333
63. Selice R, Garolla A, Pengo M, Caretta N, Ferlin A, Foresta C. The response to fsh treatment in oligozoospermic men depends on fsh receptor gene polymorphisms. Int J Androl. (2011) 34(4 Part 1):306–12. doi: 10.1111/j.1365-2605.2010.01086.x
64. Simoni M, Santi D, Negri L, Hoffmann I, Muratori M, Baldi E, et al. Treatment with human, recombinant FSH improves sperm DNA fragmentation in idiopathic infertile men depending on the FSH receptor polymorphism p.N680S: a pharmacogenetic study. Hum Reprod. (2016) 31:1960–9. doi: 10.1093/humrep/dew167
65. Grigorova M, Punab M, Poolamets O, Sõber S, Vihljajev V, Žilaitiene B, et al. Study in 1790 Baltic men: FSHR Asn680Ser polymorphism affects total testes volume. Andrology. (2013) 1:293–300. doi: 10.1111/j.2047-2927.2012. 00028.x
66. Nieschlag E, Simoni M, Gromoll J, Weinbauer GF. Role of FSH in the regulation of spermatogenesis: Clinical aspects. Clin Endocrinol. (1999) 51:139–46. doi: 10.1046/j.1365-2265.1999.00846.x
67. Ahda Y, Gromoll J, Wunsch A, Asatiani K, Zitzmann M, Nieschlag E, et al. Follicle-stimulating hormone receptor gene haplotype distribution in normozoospermic and azoospermic men. J Androl. (2005) 26:494–9. doi: 10.2164/jandrol.04186
68. Huszar G, Ozenci CC, Cayli S, Zavaczki Z, Hansch E, Vigue L. Hyaluronic acid binding by human sperm indicates cellular maturity, viability, and unreacted acrosomal status. Fertil Steril. (2003) 79 (Suppl. 3):1616–24. doi: 10.1016/S0015-0282(03)00402-3
69. Muratori M, Marchiani S, Tamburrino L, Cambi M, Lotti F, Natali I, et al. DNA fragmentation in brighter sperm predicts male fertility independently from age and semen parameters. Fertil Steril. (2015) 582–90.e4. doi: 10.1016/j.fertnstert.2015.06.005
70. Muratori M, Tamburrino L, Marchiani S, Cambi M, Olivito B, Azzari C, et al. Investigation on the origin of sperm DNA fragmentation: role of apoptosis, immaturity and oxidative stress monica. Mol Med. (2015) 21:109–122. doi: 10.2119/molmed.2014.00158
71. Schüring AN, Busch AS, Bogdanova N, Gromoll J, Tüttelmann F. Effects of the FSH-β-subunit promoter polymorphism −211G→ T on the hypothalamic-pituitary-ovarian axis in normally cycling women indicate a gender-specific regulation of gonadotropin secretion. J Clin Endocrinol Metab. (2013) 98:E82–6. doi: 10.1210/jc.2012-2780
72. Rull K, Grigorova M, Ehrenberg A, Vaas P, Sekavin A, Nõmmemees D, et al. FSHB −211 G>T is a major genetic modulator of reproductive physiology and health in childbearing age women. Hum Reprod. (2018) 33:954–66. doi: 10.1093/humrep/dey057
73. Visscher PM, Wray NR, Zhang Q, Sklar P, McCarthy MI, Brown MA, et al. 10 Years of GWAS discovery: biology, function, and translation. Am J Hum Genet. (2017) 101:5–22. doi: 10.1016/j.ajhg.2017. 06.005
74. Rohayem J, Hauffa BP, Zacharin M, Kliesch S, Zitzmann M. Testicular growth and spermatogenesis: new goals for pubertal hormone replacement in boys with hypogonadotropic hypogonadism?—A multicentre prospective study of hCG / rFSH treatment outcomes during adolescence. Clin Endocrinol. (2017) 49:75–87. doi: 10.1111/cen. 13164
75. Ding Y, Zhang X, Li J, Chen S, Zhang R, Tan W. Treatment of idiopathic oligozoospermia with recombinant human follicle-stimulating hormone: a prospective,randomized, double-blind, placebo-controlled clinical study in Chinese population. Clin Endocrinol. (2015) 83:866–71. doi: 10.1111/cen.12770
76. ICH. ICH Harmonised Tripartite Guideline. Statistical Principles for Clinical Trials. International Conference on Harmonisation E9 Expert Working Group. (1999).