A Retrospective Analysis of Background Lesions and Tissue Accountability for Male Accessory Sex Organs in Fischer-344 Rats

Abstract

Because the paired lobes (ventral, dorsal, lateral, and anterior) of the rat prostate have not been consistently sampled in many carcinogenicity and toxicity studies, comparison among different investigations has been compromised. The lack of specific site identification for prostatic lesions further lessens the value of incidences reported. We present here the lobe-specific incidences and degree of severity of background prostatic, seminal vesicular, and ampullary glandular lesions in 1768 control Fischer-344 rats from 35 recent National Toxicology Program 2-year carcinogenicity and toxicity studies conducted in 4 laboratories. The dorsal and lateral lobes were combined and considered the dorsolateral lobe where inflammation, epithelial degeneration, mucinous cysts, and edema were observed. Inflammation in the dorsolateral lobes was significantly associated with pituitary gland adenoma whose prolactin was suggested to play an important role in pathogenesis of prostatic inflammation. Epithelial degeneration, epithelial hyperplasia, inflammation, edema, and adenoma were conspicuous in the ventral lobes. Inflammation and edema occurred in the anterior lobes (coagulating glands). Inflammation, dilatation, epithelial hyperplasia, edema, and adenoma were observed in the seminal vesicles. Inflammation was also present in the ampullary glands. We suggest an optimal embedment and trimming method in rat prostate and seminal vesicle to ensure adequate, consistent sampling.

Proliferative and Nonproliferative Lesions of the Rat and Mouse Male Reproductive System

“…The change is also sometimes associated with chronic inflammation of the vesicle wall and may be secondary to ascending urinary tract infections, which are relatively common in male mice. Mucinous cystic acini (cysts) have also been described in the prostate of aging rats and mice (Suwa et al 2001(Suwa et al , 2002. Similarly, dilation of the bulbourethral glandular acini or ducts, progressing to cystic atrophy may be observed in aging rats and mice where enlarged bulbourethral glands are often sampled as gross abnormalities (Kiupel, Brown, and Sundberg 2000;Wardrip et al 1998).…”

“…The mucosa has a honeycombed structure formed by complex folding to produce irregular anastomosing channels that communicate with the central cavity; thin primary folds of the mucosa also extend out into the vesicle lumen. The epithelium is composed of pseudostratified columnar cells in the mouse and simple columnar epithelium in the rat (Suwa et al 2001(Suwa et al , 2002. The secretory material from this gland is intensely eosinophilic and constitutes 50 to 80% of the ejaculate (Creasy and Foster 2002).…”

“…Hypoplasia of the ventral and dorsolateral prostate, and seminal vesicles have been reported in male Sprague-Dawley rats exposed in utero to Di(n-butyl) phthalate (Barlow and Foster 2003). (Faccini, Abbott, and Paulus 1990;Frith and Ward 1988;Radovsky, Mitsumori, and Chapin 1999;Suwa et al 2001Suwa et al , 2002Yamate et al 1990), and it has been suggested that the accumulation of secretory product may be due to sexual inactivity and declining testosterone levels (Suwa et al 2001(Suwa et al , 2002. The change is also sometimes associated with chronic inflammation of the vesicle wall and may be secondary to ascending urinary tract infections, which are relatively common in male mice.…”

“…Depending on the secretory activity, all lobes are filled with secretory material that may appear flocculent. In the ventral lobes, the secretion is palely eosinophilic, while in the lateral lobes it stains intensely eosinophilic and in the dorsal lobes it stains intermediate between the other two lobes (Boorman, Elwell, and Mitsumori 1990;Lee and Holland 1987, Suwa et al 2001.…”

Experimental rodent models of prostatitis: limitations and potential

“…Recently, it has been found that there is a significant association between spontaneous inflammation in the dorsolateral lobes of prostate and prolactin positive pituitary gland adenomas in Fisher-344 rats; this finding supports the hypothesis that prolactin plays an important role in the pathogenesis of prostatic inflammation. 141 It has been also shown that prepubertal (postnatal days 22-32) exposure to various compounds that increase prolactin secretion, including pimozide (a dopamine antagonist), bisphenol A (a monomer of polycarbonate plastic reported to have weak estrogenic activity), and 17b-estradiol, albeit through different mechanisms, can increase the incidence of inflammation in the lateral prostate the Wistar rats. 142,143 Shyr et al 144 used daily injections of bromocryptine to depress maternal plasma and milk PRL levels in lactating rats.…”