PMID- 30768127
OWN - NLM
STAT- MEDLINE
DCOM- 20200504
LR  - 20200601
IS  - 1096-0929 (Electronic)
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 169
IP  - 2
DP  - 2019 Jun 1
TI  - Small RNAs in Rat Sperm Are a Predictive and Sensitive Biomarker of Exposure to 
      the Testicular Toxicant Ethylene Glycol Monomethyl Ether.
PG  - 399-408
LID - 10.1093/toxsci/kfz041 [doi]
AB  - Testicular histology and semen parameters are considered the gold standards when 
      determining male reproductive toxicity. Ethylene glycol monomethyl ether (EGME) 
      is a testicular toxicant with well-described effects on histopathology and sperm 
      parameters. To compare the predictivity and sensitivity of molecular biomarkers 
      of testicular toxicity to the traditional endpoints, small RNAs in the sperm were 
      analyzed by next generation RNA-sequencing (RNA-seq). Adult rats were exposed to 
      0, 50, 60, or 75 mg/kg EGME by oral gavage for 5 consecutive days. Testis 
      histology, epididymal sperm motility, and sperm small RNAs, including microRNAs 
      (miRNAs), mRNA fragments, piwi-interacting RNAs (piRNAs), and tRNA fragments 
      (tRFs), were analyzed 5 weeks after cessation of exposure. Testicular histology 
      showed a significant dose-dependent increase in retained spermatid heads (RSH), 
      while sperm motility declined with increasing dose. RNA-sequencing of sperm small 
      RNAs was used to identify significant dose-dependent changes in percent mRNA 
      fragments (of total reads), percent miRNAs (of total reads), average tRF length, 
      average piRNA length, and piRNA and tRF length-distributions. Discriminant 
      analysis showed relatively low predictivity of exposure based on RSH or motility 
      compared to the average read length of all assigned RNAs. Benchmark dose (BMD) 
      modeling resulted in a BMD of 62 mg/kg using RSH, whereas average read length of 
      all assigned RNAs resulted in a BMD of 47 mg/kg. These results showed that sperm 
      small RNAs are sensitive and predictive biomarkers of EGME-induced male 
      reproductive toxicity.
CI  - (c) The Author(s) 2019. Published by Oxford University Press on behalf of the 
      Society of Toxicology. All rights reserved. For permissions, please e-mail: 
      journals.permissions@oup.com.
FAU - Stermer, Angela R
AU  - Stermer AR
AD  - Department of pathology and laboratory medicine, Brown University, Providence, 
      Rhode Island 02912.
FAU - Reyes, Gerardo
AU  - Reyes G
AD  - Department of pathology and laboratory medicine, Brown University, Providence, 
      Rhode Island 02912.
FAU - Hall, Susan J
AU  - Hall SJ
AD  - Department of pathology and laboratory medicine, Brown University, Providence, 
      Rhode Island 02912.
FAU - Boekelheide, Kim
AU  - Boekelheide K
AD  - Department of pathology and laboratory medicine, Brown University, Providence, 
      Rhode Island 02912.
LA  - eng
GR  - P42 ES013660/ES/NIEHS NIH HHS/United States
GR  - T32 ES007272/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Biomarkers)
RN  - 0 (Ethylene Glycols)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - 9014-25-9 (RNA, Transfer)
RN  - EK1L6XWI56 (methyl cellosolve)
SB  - IM
MH  - Animals
MH  - Biomarkers/blood
MH  - Ethylene Glycols/*toxicity
MH  - Male
MH  - MicroRNAs/*analysis
MH  - No-Observed-Adverse-Effect Level
MH  - RNA, Messenger/analysis
MH  - RNA, Small Interfering/*analysis
MH  - RNA, Transfer/analysis
MH  - Rats
MH  - Rats, Inbred F344
MH  - Sequence Analysis, RNA
MH  - Spermatozoa/chemistry/*drug effects
MH  - Testis/*drug effects/pathology
PMC - PMC6934889
OTO - NOTNLM
OT  - biomarkers
OT  - preconception exposures
OT  - small RNA
OT  - sperm epigenetics
OT  - testicular toxicity
EDAT- 2019/02/16 06:00
MHDA- 2020/05/06 06:00
PMCR- 2020/06/01
CRDT- 2019/02/16 06:00
PHST- 2019/02/16 06:00 [pubmed]
PHST- 2020/05/06 06:00 [medline]
PHST- 2019/02/16 06:00 [entrez]
PHST- 2020/06/01 00:00 [pmc-release]
AID - 5320425 [pii]
AID - kfz041 [pii]
AID - 10.1093/toxsci/kfz041 [doi]
PST - ppublish
SO  - Toxicol Sci. 2019 Jun 1;169(2):399-408. doi: 10.1093/toxsci/kfz041.