Neoplastic diseases in prosimians have been sporadically reported in the literature. To provide a comprehensive review of prosimian neoplasia, a retrospective evaluation of neoplasia in a large captive prosimian colony and an extensive literature review were performed. Primates that belong to the Order Primata, Suborder Prosimii with histologic evidence of neoplasia were included. One hundred twenty-three cases of spontaneous neoplasia were identified in 101 prosimians from the Duke Lemur Center, and 124 cases were reported in 116 prosimians in the literature. Overall, this review compiled a total of 247 neoplasms in 217 prosimians. Of the 217 affected animals, 88 of 217 were males (41%), 100 of 217 were females (46%), and sex was not reported in 29 of 217 (13%). Ages ranged from 2 days to 36 years. Prosimian families represented were Lemuridae (80/217 [37%]), Cheirogaleidae (61/217 [28%]), Galagidae (44/217 [20%]), Lorisidae (28/217 [13%]), and Indriidae (4/217 [2%]). The most commonly affected species were the gray mouse lemur (Microcebus murinus) (28/217 [13%]), thick-tailed greater bush baby (Otolemur crassicaudatus) (23/217 [11%]), and black lemur (Eulemur macaco) (19/217 [9%]). Organ systems affected, in order of descending occurrence, were digestive (75/247 [30%]), reproductive (40/247 [16%]), hematopoietic (34/247 [14%]), integumentary (28/247 [11%]), endocrine (26/247 [11%]), and urinary (17/247 [7%]). The respiratory, nervous, musculoskeletal, and cardiovascular systems were infrequently affected. The most common neoplasms were hepatocellular (32/247 [13%]), lymphoma and/or leukemia (29/247 [12%]), biliary (15/247 [6%]), and mammary neoplasms (12/247 [5%]). This article should serve as a valuable reference for the types and relative frequencies of neoplasms that occur in prosimian species.
Histopathologic examination of the testis from juvenile rats is often necessary to characterize the safety of new drugs for pediatric use and is a required end point in male pubertal development and thyroid function assays. To aid in evaluation and interpretation of the immature testis, the characteristic histologic features of the developing rat testis throughout postnatal development are described and correlated with published neuroendocrine parameter changes. During the neonatal period (postnatal day [PND] 3-7), seminiferous tubules contained gonocytes and mitotically active immature Sertoli cells. Profound proliferation of spermatogonia and continued Sertoli cell proliferation occurred in the early infantile period . The spermatogonia reached maximum density forming double-layered rosettes with Sertoli cells in the late infantile period . Leptotene/zygotene spermatocytes appeared centrally as tubular lumina developed, and individual tubules segregated into stages. The juvenile period (PND 21-32) featured a dramatic increase in number and size of pachytene spermatocytes with the formation of round spermatids and loss of ''infantile'' rosette architecture. In the peri-pubertal period (PND 32-55), stage VII tubules containing step 19 spermatids were visible by PND 46. The presented baseline morphologic and endocrinologic information will help pathologists distinguish delayed development from xenobiotic effects, determine pathogenesis when confronted with nonspecific findings, and identify sensitive time points for targeted study design.
Age, and in particular young age, can significantly impact the response to toxicants in animals and can greatly influence the interpretation of tissue changes by the toxicologic pathologist. Although this applies to multiple organ systems, the current review focuses on the male reproductive system. When performing microscopic evaluation of male reproductive organs, the toxicologic pathologist must be aware of the dynamic changes in histomorphology, predominantly driven by timed hormonal alterations, at various life stages. Specific challenges pathologists face are understanding the appearance of male reproductive tissues throughout the neonatal, infantile, and juvenile developmental periods, recognizing when normal looks abnormal during tissue development, defining sexual maturity, and working with high interanimal variability in maturation rate and histologic appearance in developing large laboratory animals, such as nonhuman primates, dogs, and pigs. This review describes postnatal development of the male reproductive system in the rat, demonstrates how assessing toxicity during a defined window of postnatal development in the rat may improve definition of toxicant timing and targets, and discusses challenges associated with the interpretation of toxicity in immature large animal species. The emphasis is on key age-related characteristics that influence the interpretation of tissue changes by the toxicologic pathologist.
In response to growing concerns that environmental chemicals may have adverse effects on human health by altering the endocrine system, the Endocrine Disruptor Screening Program (EDSP), under the auspices of the United States Environmental Protection Agency (U.S. EPA), recently instituted a Tier I battery of tests including a female pubertal assay. This assay requires dosing of female rats from postnatal day (PND) 22 through PND 42 (or 43), the period of pubertal development in the rat, to identify test articles that may have estrogenic or antiestrogenic effects, or may alter hormones or neurotransmitters. While certain landmarks in female rat reproductive development are published, little is published on the microscopic appearance of the female reproductive tract during prepubertal and pubertal development. In this study, reproductive tissues from three female Sprague-Dawley rats were collected each day from PND 20 through PND 50, such that tissues from a total of 93 rats were collected throughout the prepubertal and pubertal period. Tissues were formalin-fixed, trimmed, paraffin-embedded, sectioned at 5-mm thickness, and examined microscopically. The major histologic features of the female reproductive tract throughout this critical period were described in detail. This information will help pathologists interpret findings observed in female pubertal assays.
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