Sprague-Dawley Rats—12 weeks of age

SIGNALMENT: (age, breed, sex, species, and scientific name) 
Sprague-Dawley rats, approximately 12 weeks of age.


TREATMENT PROTOCOL (including test  compound):
Rats were administered Compound X or Compound Y daily by the oral gavage route for 10 days.  Animals were sacrificed on Day 5 and Day 10; testis was fixed in formalin, processed and stained by PAS method. 

Compound X= 1,3-dinitrobenzene
Compound Y= ethylene glycol monomethyl ether

GROSS PATHOLOGY: 
No gross observations were done at necropsy.

LABORATORY RESULTS: (clinical pathology, microbiology, etc…)
None

MORPHOLOGIC DIAGNOSIS AND ETIOLOGY: 
Compound X: Degeneration, seminiferous tubule, testis. 1,3-dintrobenzene
Compound Y: Degeneration, seminiferous tubule, testis. Ethylene glycol monomethyl ether

CONTRIBUTOR'S COMMENTS:  
1,3-dinitrobenzene study (Compound X): Figure 2 shows a Stage I seminiferous tubule with enlarged, degenerative spermatocytes surrounded by clear spaces possibly representing degeneration/vacuolation of adjacent Sertoli cell cytoplasm. The possibility of artifactual vacuolation of Sertoli cell (shrinkage artifact) cannot be excluded. Figure 3 shows an early stage seminiferous tubule (possibly stage I) with extensive vacuolation of Sertoli cells and degeneration/loss of many spermatocytes and most round spermatids. Although the Sertoli cell is considered to be the primary target cell for dinitrobenzene, pachytene spermatocytes are also affected as evident in Figure 3.

Ethylene glycol monomethyl ether (Compound Y): Figure 4 shows a Stage I seminiferous tubule with degeneration of pachytene spermatocytes and presence a multinucleated giant cell (syncytia of round spermatids). Figure 5 shows a Stage V-VI seminiferous tubule with Step 18-19 spermatids adjacent to a single layer of type B spermatagonia and Sertoli cells. There is a complete absence of pachytene spermatocytes and round spermatids in this seminiferous tubule. The pachytene spermatocyte is considered the primary target cell for this glycol ether compound.

REFERENCES:
1. Blackburn, DM, et al. 1988. A Comparison of the Effects of the Three Isomers of Dintrobenzene on the Testis in the Rat. Tox Appl Pharmacol 92: 54-64.
 

2. Chapin, RE, et al. 1985. The Recovery of the Testis over 8 Weeks after Short-Term Dosing with EGME: Histology, Cell-Specific Enzymes, and rete Testis Fluid Protein. Fund. Appl Tox. 5: 515-525.

3. Chapin, RE. 1984. The effects of Ethylene Glycol Monomethyl Ether on Testicular Histology in F344 Rats. J Androl 5:369-380.

4. Creasy, D. 1997. Evaluation of Testicular Toxicity in Safety Evaluation Studies: The Appropriate Use of Spermatogenic Staging. Toxicol Pathol 25(2): 119-131.

5. Reader, SCJ, et al., 1991. Acute Testicular Toxicity of 1,3-Dintrobenze and EGME in the Rat: Evaluation of Biochemical Effect and Hormonal Responses. Fund. Appl Tox. 16: 61-70.

 

Figure 1.jpg

Sprague-Dawley rat, male. PAS staining. 40X magnification. Control animal.

Figure 2.jpg

Sprague-Dawley rat exposed to Compound X, Day 5. PAS staining. 40X magnification.

Figure 3.jpg

Sprague-Dawley rat exposed to Compound X, Day 10. PAS staining. 40X magnification.

Figure 4.jpg

Sprague-Dawley rat exposed to Compound Y, Day 5. PAS staining. 40X magnification.

Figure 5.jpg

Sprague-Dawley rat exposed to Compound Y, Day 10. PAS staining. 40X magnification.


 

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