A quantitative study of stage-specific spermatocyte damage following administration of ethylene glycol monomethyl ether in the rat

Creasy, Dianne M.; Flynn, John C.; Gray, Tim J.B.; Butler, W. H.

doi:10.1016/0014-4800(85)90069-3

Cited by 82 publications

(26 citation statements)

References 22 publications

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“…Although this may appear a relatively minor change, some studies have shown that this can be the only morphological abnormality associated with infertility (39,56). In the case of boric acid (39), the dose level producing spermatid retention (3,000/4,500 ppm) and the dose level producing germ cell depletion (6, Sertoli cell toxicant (9), are very similar to those described for 2-methoxyethanol, a spermatocyte toxicant (16). This is due to the fact that, in the case of dinitrobenzene, the initial Sertoli cell vacuolation is rapidly followed by a cell-specific germ cell degeneration, affecting the pachytene spermatocytes.…”

Section: Spermatogenesismentioning

confidence: 66%

“…In the early stages of damage, many chemicals have been shown to have cellspecific effects that are restricted to specific stages of the spermatogenic cycle, but this specificity is very dependent on dose and duration of dosing (Table II). Studies using different dose levels of 2-methoxyethanol (up to 500 mg/kg/day) for different durations of dosing demonstrate a range of sensitivity for pachytene spermatocytes : dividing spermatocytes > early pachytene spermatocytes > late pachytene spermatocytes > midpachytene spermatocytes (16,19) (Table II and Fig. 5).…”

Section: Spermatogenesismentioning

confidence: 99%

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Review Article: Evaluation of Testicular Toxicity in Safety Evaluation Studies: The Appropriate Use of Spermatogenic Staging

1997

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Section: Spermatogenesismentioning

confidence: 66%

Section: Spermatogenesismentioning

confidence: 99%

Review Article: Evaluation of Testicular Toxicity in Safety Evaluation Studies: The Appropriate Use of Spermatogenic Staging

1997

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“…Previous studies have demonstrated that administration of MAA to rats results in a cell-and stage-specific loss of pachytene spermatocytes (4,6,7,9,29,30). However, the mechanisms by which MAA exerts this apparently selective effect are unknown.…”

Section: Discussionmentioning

confidence: 99%

Rat Pachytene Spermatocytes Down-Regulate a Polo-Like Kinase and Up-Regulate a Thiol-Specific Antioxidant Protein, Whereas Sertoli Cells Down-Regulate a Phosphodiesterase and Up-Regulate an Oxidative Stress Protein after Exposure to Methoxyethanol and Methoxyacetic Acid

Syed¹

1998

Endocrinology

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ABSTRACT2-Methoxyethanol (ME) and its metabolite, methoxyacetic acid (MAA), produce testicular lesions characterized by pachytene spermatocyte degeneration. To understand the molecular basis of this action on meiotic prophase cells, mRNA differential display was used to identify gene expression changes in control and treated cells. When pachytene spermatocytes were cultured with 5 mM ME or 5 mM MAA for 24 h, two complementary DNAs (cDNAs), of 557 nucleotides (clone 5) and 388 nucleotides (clone 6), were up-regulated; and a cDNA of 648 nucleotides (clone 1) was down-regulated. The altered expression pattern shown by differential display was confirmed by Northern blotting. Sequence analyses indicate that clones 1 and 6 have 83% and 79% homology at the nucleotide level to a polo-like kinase and a thiol-specific antioxidant, respectively. Clone 5 shows no homology to any known gene in the database. Messenger RNAs (mRNAs) encoding the thiol-specific antioxidant and clone 5 are up-regulated within 30 min of the addition of MAA, whereas the polo-like kinase mRNA decreased to undetectable levels after 6 h. Changes in Sertoli cell gene expression were also detected when Sertoli cells were cultured with 5 mM ME or MAA for 24 h. Two cDNAs, of 367 nucleotides (clone 2) and 676 nucleotides (clone 3), were up-regulated; and a cDNA of 538 nucleotides (clone 4) was down-regulated. Homology searches revealed that clones 3 and 4 have 90 and 91% homology at the nucleotide level to an oxidative stress protein and a phosphodiesterase (PDE), respectively. Northern blotting confirmed the differential display expression pattern for the PDE and oxidative stress protein. mRNAs for the latter were induced within 30 min, and PDE mRNAs were downregulated within one h, after the addition of MAA. To determine whether the changes in gene expression seen with cells in culture also occur in vivo, rats were given a single oral dose of 250 mg/kg ME or MAA. After 24 h, total testis RNAs from control and treated rats were purified and hybridized. The expression patterns seen in vivo for the differentially expressed cDNAs were identical to those seen in vitro. We conclude that, although pachytene spermatocytes seem to be selectively affected by ME and MAA, changes in gene expression are also detected in Sertoli cells, suggesting that the action(s) of ME or MAA on pachytene spermatocytes could be mediated through Sertoli cells. (Endocrinology 139: 3503-3511, 1998)

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“…Many toxicants have been reported to inhibit spermiation in rodents by disrupting the hypothalamic-pituitary axis (Beardsley and O'Donnell, 2003;Saito et al, 2000). These include phthalate esters (Creasy et al, 1985;Creasy, 2001;Moffit et al, 2007;Richburg and Boekelheide, 1996), 1,3-dinitrobenzene (Hess, 1990) and methyl 2-benzimidazole carbamate (Correa and Miller, 2001;Nakai and Hess, 1997;Winder et al, 2001), all indicating the suppression of androgen production. Similar effects produced by boric acid (Ku et al, 1993;Kudo et al, 2000), halogenated acid (Linder et al, 1990(Linder et al, , 1994, methyl methanesulfonate (Kuriyama et al, 2005;Ozawa et al, 2000;Richburg and Boekelheide, 1996) and tributylin chloride (Omura et al, 2001) indicate estrogenlike effects.…”

Section: Discussionmentioning

confidence: 99%

Testicular spermiation failure in rats exposed prenatally to 3,3',4,4',5-pentachlorobiphenyl

et al. 2010

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-Testicular spermatogenesis was studied in 7-, 10-, 13-and 17-week-old Sprague-Dawley rats whose dams had been administered intragastrically with 2.5, 25, or 250 ng of 3,3′,4,4′,5-pentachlorobiphenyl (PCB126) or vehicle on days 13-19 of gestation. The 250 ng groups among the 7-, 10-and 13-week-old offspring showed significant inhibition of mature spermatid release (spermiation), but 17-weekold offspring did not show this. These alterations were not observed in other PCB126 and vehicle groups, and no germ cell or Sertoli cell degeneration were observed in any group. Spermiation failure at puberty appeared in those rats born to dams exposed 250 ng/kg PCB126 on days 13-19 of gestation was reversible change that recovered at adulthood. Because the serum testosterone, luteinizing hormone and folliclestimulating hormone concentrations were similar in the PCB126 and vehicle groups, a direct endocrine cause for the observed effects was unlikely.

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A quantitative study of stage-specific spermatocyte damage following administration of ethylene glycol monomethyl ether in the rat

Cited by 82 publications

References 22 publications

Review Article: Evaluation of Testicular Toxicity in Safety Evaluation Studies: The Appropriate Use of Spermatogenic Staging

Review Article: Evaluation of Testicular Toxicity in Safety Evaluation Studies: The Appropriate Use of Spermatogenic Staging

Rat Pachytene Spermatocytes Down-Regulate a Polo-Like Kinase and Up-Regulate a Thiol-Specific Antioxidant Protein, Whereas Sertoli Cells Down-Regulate a Phosphodiesterase and Up-Regulate an Oxidative Stress Protein after Exposure to Methoxyethanol and Methoxyacetic Acid

Testicular spermiation failure in rats exposed prenatally to 3,3',4,4',5-pentachlorobiphenyl

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