Relationship of interstitial edema with L-cysteine-induced sperm granulomas in the pubertal rat epididymis.
Although the pathogenesis of sperm granulomas is complicated, the leakage of spermatozoa into extraluminal tissues is regarded as a crucial event. It has been previously shown that pubertal rats injected with L-cysteine develop interstitial edema followed by sperm granulomas in the epididymis. In this study we investigated the relationships between these two lesions in 6-week old rats given daily intraperitoneal injections of L-cysteine (1,000 mg/kg body weight) for 4 weeks. Rats were examined during weeks 0, 1, 2, 3 and 4 after the first injection. Interstitial edema (moderate or severe) and sperm granulomas were seen in the corpus and cauda epididymis of L-cysteine-treated rats in study weeks 2, 3, and 4. There was no marked alteration of basement membrane of the epididymal ducts in the edematous tissues as shown by immunohistochemistry with an antilaminin antibody. However, the extravasation of Evans blue dye given I hour before necropsy suggested that the severe interstitial edema was due to increased vascular permeability. In addition, a small number of neutrophils were seen in the edematous tissues, suggesting that they might play a role in the increased vascular permeability and leakage of epididymal fluid. Interestingly, slight interstitial edema was observed in the caput epididymis in both control and L-cysteine-treated rats in early study weeks 0, 1, and 2. It is speculated that this change was related to the leakage of epididymal fluid due to increased intraluminal pressure depending on rat epididymal maturation. Taken together, these findings suggest that the severe interstitial edema results from increased vascular permeability. This, along with increased intraluminal pressure, might be the trigger for duct rupture, the prerequisite for sperm granuloma formation associated with excessive doses of L-cysteine.
Sawamoto
Osamu
O
Division of Pharmacology, Drug Safety and Metabolism, Otsuka Pharmaceutical Factory, Inc., Tokushima, Japan. sawamoos@otsukakj.co.jp
Kurisu
Kazunobu
K
Kuwamura
Mitsuru
M
Kotani
Takao
T
Yamate
Jyoji
J
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D004396:Coloring Agents / Q000493:pharmacokinetics; D003545:Cysteine / Q000008:administration & dosage / Q000633:toxicity*; D004195:Disease Models, Animal; D004487:Edema / Q000378:metabolism / Q000473:pathology*; D004822:Epididymis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005070:Evans Blue / Q000493:pharmacokinetics; D005119:Extravasation of Diagnostic and Therapeutic Materials; D006099:Granuloma / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D007274:Injections, Intraperitoneal; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013094:Spermatozoa / Q000187:drug effects / Q000473:pathology*; D013733:Testicular Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology*
D004396:Coloring Agents; D005070:Evans Blue; D003545:Cysteine