SOT Symposium Highlight: Translatable Indicators of Testicular Toxicity: Inhibin B, MicroRNAs, and Sperm Signatures

Overview

Journal Toxicol Sci

Publisher Oxford University Press

Specialty Toxicology

Date 2013 Sep 21

PMID 24052563

Citations 6

Authors

Edward Dere

Linnea M Anderson

Michelle Coulson

Barry S McIntyre

Kim Boekelheide

Robert E Chapin

Affiliations

Soon will be listed here.

Abstract

Testicular toxicity is an important safety endpoint in drug development and risk assessment, but reliable and translatable biomarkers for predicting injury have eluded researchers. However, this area shows great potential for improvement, with several avenues currently being pursued. This was the topic of a symposium session during the 2013 Society of Toxicology Annual Meeting in San Antonio, TX, entitled "Translatable Indicators of Testicular Toxicity: Inhibin B, MicroRNAs, and Sperm Signatures." This symposium brought together stakeholders from academia, government, and industry to present the limitations and drawbacks of currently used indicators of injury and discussed the ongoing efforts in developing more predictive biomarkers of injury. The presentations highlighted the early challenges of using circulating inhibin B and microRNA levels, and sperm messenger RNA transcript abundance and DNA methylation profiles, as novel biomarkers of testicular toxicity.

Citing Articles

Circulating microRNAs as promising testicular translatable safety biomarkers: current state and future perspectives.

Zhang J, Campion S, Catlin N, Reagan W, Palyada K, Ramaiah S Arch Toxicol. 2023; 97(4):947-961.

PMID: 36795116 PMC: 9933818. DOI: 10.1007/s00204-023-03460-0.

The Abscopal Effects of Cranial Irradiation Induce Testicular Damage in Mice.

Guo L, Qin T, Liu L, Lai P, Xue Y, Jing Y Front Physiol. 2021; 12:717571.

PMID: 34867437 PMC: 8637864. DOI: 10.3389/fphys.2021.717571.

Small RNAs in Rat Sperm Are a Predictive and Sensitive Biomarker of Exposure to the Testicular Toxicant Ethylene Glycol Monomethyl Ether.

Stermer A, Reyes G, Hall S, Boekelheide K Toxicol Sci. 2019; 169(2):399-408.

PMID: 30768127 PMC: 6934889. DOI: 10.1093/toxsci/kfz041.

From the Cover: Sperm Molecular Biomarkers Are Sensitive Indicators of Testicular Injury following Subchronic Model Toxicant Exposure.

Dere E, Wilson S, Anderson L, Boekelheide K Toxicol Sci. 2016; 153(2):327-40.

PMID: 27466211 PMC: 5036622. DOI: 10.1093/toxsci/kfw137.

MicroRNA profiles in a monkey testicular injury model induced by testicular hyperthermia.

Sakurai K, Mikamoto K, Shirai M, Iguchi T, Ito K, Takasaki W J Appl Toxicol. 2016; 36(12):1614-1621.

PMID: 27071960 PMC: 5108483. DOI: 10.1002/jat.3326.

References

Miller D, Ostermeier G . Towards a better understanding of RNA carriage by ejaculate spermatozoa. Hum Reprod Update. 2006; 12(6):757-67. DOI: 10.1093/humupd/dml037. View

Lee R, Feinbaum R, Ambros V . The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993; 75(5):843-54. DOI: 10.1016/0092-8674(93)90529-y. View

Zernecke A, Bidzhekov K, Noels H, Shagdarsuren E, Gan L, Denecke B . Delivery of microRNA-126 by apoptotic bodies induces CXCL12-dependent vascular protection. Sci Signal. 2009; 2(100):ra81. DOI: 10.1126/scisignal.2000610. View

Maatouk D, Loveland K, McManus M, Moore K, Harfe B . Dicer1 is required for differentiation of the mouse male germline. Biol Reprod. 2008; 79(4):696-703. DOI: 10.1095/biolreprod.108.067827. View

Coulson M, Mitchard T, Bickerton S, Harris J, Betts C, Stewart J . The inhibin B response in male rats treated with a GnRH agonist and an endothelin receptor antagonist. Birth Defects Res B Dev Reprod Toxicol. 2013; 98(1):82-90. DOI: 10.1002/bdrb.21044. View

Amann R, Chapman P . Total sperm per ejaculate of men: obtaining a meaningful value or a mean value with appropriate precision. J Androl. 2009; 30(6):642-9. DOI: 10.2164/jandrol.108.006825. View

ZINKHAM W, Blanco A, CLOWRY Jr L . AN UNUSUAL ISOZYME OF LACTATE DEHYDROGENASE IN MATURE TESTES: LOCALIZATION, ONTOGENY, AND KINETIC PROPERTIES. Ann N Y Acad Sci. 1964; 121:571-88. DOI: 10.1111/j.1749-6632.1964.tb14227.x. View

Orlando C, Casano R, Caldini A, Forti G, Barni T, Bonfanti L . Measurement of seminal LDH-X and transferrin in normal and infertile men. J Androl. 1988; 9(3):220-3. DOI: 10.1002/j.1939-4640.1988.tb01040.x. View

Howard R, Aist J . Cytoplasmic microtubules and fungal morphogenesis: ultrastructural effects of methyl benzimidazole-2-ylcarbamate determined by freeze-substitution of hyphal tip cells. J Cell Biol. 1980; 87(1):55-64. PMC: 2110702. DOI: 10.1083/jcb.87.1.55. View

10.

Chapin R, Morrissey R, Gulati D, Hope E, Barnes L, Russell S . Are mouse strains differentially susceptible to the reproductive toxicity of ethylene glycol monomethyl ether? A study of three strains. Fundam Appl Toxicol. 1993; 21(1):8-14. DOI: 10.1006/faat.1993.1065. View

11.

Quinlan R, Pogson C, Gull K . The influence of the microtubule inhibitor, methyl benzimidazol-2-yl-carbamate (MBC) on nuclear division and the cell cycle in Saccharomyces cerevisiae. J Cell Sci. 1980; 46:341-52. DOI: 10.1242/jcs.46.1.341. View

12.

Pfaff T, Rhodes J, Bergmann M, Weinbauer G . Inhibin B as a marker of sertoli cell damage and spermatogenic disturbance in the rat. Birth Defects Res B Dev Reprod Toxicol. 2013; 98(1):91-103. DOI: 10.1002/bdrb.21046. View

13.

Linder R, Hess R, Strader L . Testicular toxicity and infertility in male rats treated with 1,3-dinitrobenzene. J Toxicol Environ Health. 1986; 19(4):477-89. DOI: 10.1080/15287398609530946. View

14.

Odet F, Duan C, Willis W, Goulding E, Kung A, Eddy E . Expression of the gene for mouse lactate dehydrogenase C (Ldhc) is required for male fertility. Biol Reprod. 2008; 79(1):26-34. PMC: 2574787. DOI: 10.1095/biolreprod.108.068353. View

15.

Draper R, Waterfield C, York M, Timbrell J . Studies on the muscle toxicant 2,3,5,6-tetramethyl p-phenylenediamine: effects on various biomarkers including urinary creatine and taurine. Arch Toxicol. 1994; 69(2):111-7. DOI: 10.1007/s002040050145. View

16.

Lee I, Ajay S, In Yook J, Kim H, Hong S, Kim N . New class of microRNA targets containing simultaneous 5'-UTR and 3'-UTR interaction sites. Genome Res. 2009; 19(7):1175-83. PMC: 2704433. DOI: 10.1101/gr.089367.108. View

17.

Wijchman J, de Wolf B, Graafe R, Arts E . Variation in semen parameters derived from computer-aided semen analysis, within donors and between donors. J Androl. 2001; 22(5):773-80. View

18.

Andersson A, Muller J, Skakkebaek N . Different roles of prepubertal and postpubertal germ cells and Sertoli cells in the regulation of serum inhibin B levels. J Clin Endocrinol Metab. 1998; 83(12):4451-8. DOI: 10.1210/jcem.83.12.5360. View

19.

Sasaki J, Chapin R, Hall D, Breslin W, Moffit J, Saldutti L . Incidence and nature of testicular toxicity findings in pharmaceutical development. Birth Defects Res B Dev Reprod Toxicol. 2011; 92(6):511-25. DOI: 10.1002/bdrb.20338. View

20.

Chan D, Delbes G, Landry M, Robaire B, Trasler J . Epigenetic alterations in sperm DNA associated with testicular cancer treatment. Toxicol Sci. 2011; 125(2):532-43. DOI: 10.1093/toxsci/kfr307. View