Methoxyacetic acid-induced spermatocyte death is associated with histone hyperacetylation in rats

Biology of Reproduction
Michael G WadeCarole Yauk

Abstract

We used high-density microarrays to evaluate the possible mechanisms by which 2-methoxyacetic acid (MAA) disrupts spermatogenesis. Levels of mRNA transcripts were determined in total RNA isolated from testes of MAA-treated (650 mg/kg i.p.) or concurrent control rats killed 4, 8, 12, or 24 h postexposure (PE). Germ cell death was examined in testis sections using in situ staining for DNA fragmentation. MAA treatment caused increased death of pachytene spermatocytes starting 8 h PE and increasing dramatically at 12 and 24 h PE. Microarray results indicated that at 4 h PE the transcript levels of seven different genes were significantly overrepresented in the testes of MAA-exposed animals. One gene (histone H1 zero [H1f0]) was significantly overrepresented in MAA-treated samples at 4, 8, and 12 h PE. Because expression of this gene has been associated with increased acetylation of core histones, we examined MAA-induced changes in the acetylation of histones H4 (HISTH4) and H3 (HISTH3) in testis nuclear protein. Western blots of acid-extracted testis nuclei indicated that the levels of tetraacetyl histone H4 (4acHIST1H4) and of diacetyl histone H3 (2acHIST1H3) were elevated by MAA treatment at 4, 8, and 12 h PE. Using the same anti...Continue Reading

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Citations

Jul 10, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Makoto TakeiLining Guo
Sep 25, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Glenn H Cantor
Jun 23, 2010·Reproductive Biology and Endocrinology : RB&E·Gargi BagchiDavid J Waxman
May 27, 2015·International Journal of Molecular Sciences·Keshab R ParajuliZongbing You
Jan 24, 2016·Reproductive Toxicology·Keith M GoldsteinThomas K Baker
May 7, 2014·Birth Defects Research. Part B, Developmental and Reproductive Toxicology·Caroline Dayan, Barbara F Hales
Oct 20, 2011·The Journal of Toxicological Sciences·Tamio FukushimaTakemi Yoshida
Jan 27, 2017·International Journal of Molecular Sciences·Zhe ZhangHui Jiang
May 16, 2017·Drug and Chemical Toxicology·Takuya MatsuyamaKazuhiko Mori
Nov 13, 2009·Biology of Reproduction·Sarah Kimmins
Feb 16, 2019·Toxicological Sciences : an Official Journal of the Society of Toxicology·Angela R StermerKim Boekelheide
Oct 23, 2017·Occupational and Environmental Medicine·Charline WarembourgRonan Garlantézec
Mar 15, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Rong-Yi ChenZongbing You

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