Sperm Toolbox-A selection of small molecules to study human spermatozoa.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Sperm Motility* ; Semen*; Humans ; Male ; Spermatozoa/metabolism ; Acrosome Reaction ; Fertility

Male contraceptive options and infertility treatments are limited, and almost all innovation has been limited to updates to medically assisted reproduction protocols and methods. To accelerate the development of drugs that can either improve or inhibit fertility, we established a small molecule library as a toolbox for assay development and screening campaigns using human spermatozoa. We have profiled all compounds in the Sperm Toolbox in several automated high-throughput assays that measure stimulation or inhibition of sperm motility or the acrosome reaction. We have assayed motility under non-capacitating and capacitating conditions to distinguish between pathways operating under these different physiological states. We also assayed cell viability to ensure any effects on sperm function are specific. A key advantage of our studies is that all compounds are assayed together in the same experimental conditions, which allows quantitative comparisons of their effects in complementary functional assays. We have combined the resulting datasets to generate fingerprints of the Sperm Toolbox compounds on sperm function. The data are included in an on-line R-based app for convenient querying.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Gruber et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Biochem Pharmacol. 2020 Dec;182:114212. (PMID: 32866455)
Proc Natl Acad Sci U S A. 2004 Nov 23;101(47):16501-6. (PMID: 15546993)
ChemMedChem. 2022 Aug 3;17(15):e202000499. (PMID: 35644882)
Endocrinology. 2011 Jun;152(6):2492-502. (PMID: 21505053)
Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):17173-8. (PMID: 12477936)
ChemMedChem. 2017 Nov 22;12(22):1857-1865. (PMID: 28952188)
Contraception. 2002 Apr;65(4):259-63. (PMID: 12020773)
Hum Reprod. 1994 Apr;9(4):664-8. (PMID: 8046020)
Biol Reprod. 2020 Aug 21;103(3):630-642. (PMID: 32412043)
Mol Hum Reprod. 2016 Jun;22(6):410-26. (PMID: 26921398)
Nat Protoc. 2016 Sep;11(9):1757-74. (PMID: 27560178)
ACS Chem Biol. 2019 Dec 20;14(12):2943. (PMID: 31697462)
J Histochem Cytochem. 1974 Oct;22(10):981-5. (PMID: 4139184)
ACS Infect Dis. 2022 Apr 8;8(4):713-720. (PMID: 35286809)
J Pharmacol Exp Ther. 2022 Sep;382(3):299-312. (PMID: 35779861)
PLoS Biol. 2019 Aug 13;17(8):e3000398. (PMID: 31408454)
Hum Reprod. 2010 Feb;25(2):317-27. (PMID: 19923167)
Mutat Res. 1988 Feb;204(2):269-76. (PMID: 3278217)
Elife. 2020 Jan 28;9:. (PMID: 31987071)
Theriogenology. 2019 Sep 15;136:118-130. (PMID: 31254725)
Proc Natl Acad Sci U S A. 2023 Jan 24;120(4):e2212338120. (PMID: 36649421)
Future Med Chem. 2015;7(14):1901-17. (PMID: 26397018)
Nature. 2015 Jun 18;522(7556):315-20. (PMID: 26085270)
J Med Chem. 2018 Mar 8;61(5):1800-1820. (PMID: 29291372)
Proc Natl Acad Sci U S A. 2017 May 30;114(22):5743-5748. (PMID: 28507119)
Ther Adv Reprod Health. 2023 Mar 8;17:26334941221138323. (PMID: 36909934)
Andrology. 2016 Nov;4(6):1073-1083. (PMID: 27696749)
ChemMedChem. 2014 Apr;9(4):823-32. (PMID: 24616449)
J Physiol. 2012 Jun 1;590(11):2659-75. (PMID: 22473777)
J Med Chem. 2023 Feb 9;66(3):1928-1940. (PMID: 36701569)
ACS Pharmacol Transl Sci. 2022 Dec 02;6(1):115-127. (PMID: 36654752)
J Androl. 2009 Jul-Aug;30(4):469-74. (PMID: 19201696)
Nat Chem Biol. 2011 Apr;7(4):203-5. (PMID: 21378983)
J Biol Chem. 2020 Sep 18;295(38):13181-13193. (PMID: 32703901)
Biol Reprod. 2020 Aug 4;103(2):176-182. (PMID: 32307523)
J Androl. 1993 Mar-Apr;14(2):132-41. (PMID: 8514619)
Br J Pharmacol. 2019 Dec;176(23):4521-4536. (PMID: 31368510)
PLoS Biol. 2018 Jul 3;16(7):e2005970. (PMID: 29969450)
Mol Hum Reprod. 2017 Feb 10;23(2):106-115. (PMID: 28025393)
Eur J Pharm Sci. 2018 May 30;117:313-320. (PMID: 29496533)
Nat Methods. 2012 Feb 28;9(3):245-53. (PMID: 22373911)
Nat Med. 2017 Apr 7;23(4):405-408. (PMID: 28388612)
Pharmacol Ther. 2016 Jan;157:105-11. (PMID: 26593445)
Eur J Med Chem. 2016 Jun 10;115:275-90. (PMID: 27084496)
Contracept X. 2019 Apr 25;1:100007. (PMID: 32550526)
J Androl. 1995 Jan-Feb;16(1):36-46. (PMID: 7768751)
Nat Protoc. 2023 Jul;18(7):1981-2013. (PMID: 37344608)
Biochemistry. 1997 Apr 1;36(13):3811-9. (PMID: 9092810)
Cell. 2012 Aug 17;150(4):673-84. (PMID: 22901802)
Hum Reprod. 2014 Oct 10;29(10):2123-35. (PMID: 25124668)
Science. 2004 Nov 12;306(5699):1194-8. (PMID: 15539606)
Hum Reprod. 2022 Mar 01;37(3):466-475. (PMID: 35048946)
Biol Reprod. 2018 Jun 1;98(6):784-794. (PMID: 29546268)
Proc Natl Acad Sci U S A. 2018 Jan 16;115(3):E344-E346. (PMID: 29305558)
Biol Reprod. 2020 Aug 4;103(2):411-426. (PMID: 32529252)
ACS Chem Biol. 2011 Oct 21;6(10):1021-8. (PMID: 21812418)
Eur J Med Chem. 2022 Dec 5;243:114709. (PMID: 36087385)
Science. 2023 Apr 14;380(6641):154-158. (PMID: 37053322)
Nat Chem Biol. 2016 Oct;12(10):838-44. (PMID: 27547922)
Sci Rep. 2015 Sep 14;5:14077. (PMID: 26365828)
Nat Commun. 2023 Feb 14;14(1):637. (PMID: 36788210)
J Med Chem. 2022 Apr 14;65(7):5606-5624. (PMID: 35303411)
J Biol Chem. 2016 Apr 29;291(18):9776-84. (PMID: 26961873)
Mol Cell Proteomics. 2015 Apr;14(4):1104-12. (PMID: 25693802)
Oncotarget. 2017 Sep 5;8(53):91445-91458. (PMID: 29207656)
PLoS One. 2009 Aug 31;4(8):e6844. (PMID: 19718436)
Development. 2016 Jul 1;143(13):2325-33. (PMID: 27226326)
Int J Mol Sci. 2022 Sep 24;23(19):. (PMID: 36232560)

Date Created: 20240220 Date Completed: 20240222 Latest Revision: 20240222

20240222

PMC10878532

10.1371/journal.pone.0297666

38377053