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

Creasy, Dianne M.

doi:10.1177/019262339702500201

Cited by 184 publications

(109 citation statements)

References 53 publications

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“…The relationships among germ cells as they mature coordinately have been recognized and described in terms of stages (represented by Roman numerals I to XIV in the rat; I to XII in the mouse), which constitute a useful tool for testicular microscopic examination (Creasy 1997). Knowledge of the cellular relationships occurring during the spermatogenic cycle (stage-aware evaluation) aids in recognition of absent cells and detection of subtle changes restricted to specific points in spermatogenesis.…”

Section: Cellular Relationships and Stage-aware Examinationmentioning

confidence: 99%

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

Creasy

Bube

Rijk³

et al. 2012

Toxicol Pathol

206

198

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The INHAND Project (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) is a joint initiative of the Societies of Toxicologic Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP), and North America (STP) to develop an internationally accepted nomenclature for proliferative and nonproliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature and differential diagnosis for classifying microscopic lesions observed in the male reproductive system of laboratory rats and mice, with color microphotographs illustrating examples of some lesions. The standardized nomenclature presented in this document is also available for society members electronically on the Internet (http://goreni.org). Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous and aging lesions as well as lesions induced by exposure to test materials. A widely accepted and utilized international harmonization of nomenclature for lesions of the male reproductive system in laboratory animals will decrease confusion among regulatory and scientific research organizations in different countries and provide a common language to increase and enrich international exchanges of information among toxicologists and pathologists.

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Section: Cellular Relationships and Stage-aware Examinationmentioning

confidence: 99%

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

Creasy

Bube

Rijk³

et al. 2012

Toxicol Pathol

206

198

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“…In these studies, the male reproductive tract is a potential target system and one of the important systems to be evaluated for pharmacological activity and toxicity. Histopathology is acknowledged as a sensitive endpoint for detecting testicular toxicity (Creasy, 1997). For this purpose it is essential to distinguish drug-induced histological changes from the normal variation.…”

Section: Introductionmentioning

confidence: 99%

Spermatogenesis in the Cynomolgus Monkey (Macaca fascicularis): A Practical Guide for Routine Morphological Staging

Dreef¹,

Esch²,

Rijk³

2007

Toxicol Pathol

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The cynomolgus monkey (Macaca fascicularis) is widely used in regulatory toxicity studies. Especially in studies on male contraception, the male reproductive tract can be an important target system. The aim of the present paper is to describe a practical approach for morphological staging of spermatogenesis in routinely prepared paraffin sections. Results obtained using this approach could help to determine possible drug-related effects on spermatogenesis. As a guide to the investigators, photomicrographs of Bouin-fixed, paraffin-embedded and H&E or PAS stained sections from testis tissue are presented to illustrate the twelve successive morphological stages (cell associations) of normal spermatogenesis. Sexually immature or peripubertal monkeys sometimes are included in toxicity studies. Since the morphological features of the testes of such monkeys can be mistaken for treatment-related abnormalities, the morphologic characteristics of these testes are described and discussed briefly.

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“…This analysis allowed a comparative study between the interstitial tissue and seminiferous tubules, interacting in the remodeling and adaptation to different factors involved in spermatogenesis (MEISTRICH, 1986;CREASY, 1997). However, few studies in bulls have correlated these characteristics with the degeneration of seminiferous epithelium.…”

Section: Resultsmentioning

confidence: 99%

Histopathological and histomorphometric testicular characteristics associated to reproductive condition in Bos indicus (Nellore) bulls

et al. 2015

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The aim of this study was to evaluate morphological, morphometric and functional aspects of spermatogenesis based on reproductive conditions of Nellore bulls. The study used 25 bulls Bos indicus (Nellore), which were classified as satisfactory (n=10) and unsatisfactory (n=15) for reproduction. After orchiectomy, fragments of the right testis of each animal were processed routinely and stained with hematoxylin and eosin (HE) and periodic acid-Schiff (PAS). The slides were analyzed in bright field microscopy at different magnifications. The tubular segments were classified into four levels (normal, mild and moderate degeneration, severe degeneration, and tubular hypoplasia) based on the organization and architecture of the tubular tissue. The average height of the seminiferous epithelium, the average thickness of propria tunic and the average tubular diameter were obtained and the proportion of seminiferous tubules, interstitial tissue, lymphatic vessel and blood vessel of each bull testicle were recorded. Furthermore, the frequency of the three classifications of the spermatogenic cycle A, B and C (A = group of stages I, II, and III which comprise the initial phases of the cycle and mitotic proliferation, B = group of stages IV and V, which comprise intermediate phases and intensive mitosis, C = group stages VI, VII and VIII which comprise the final phases and post-meiosis) was compared. The results showed that the degenerative changes in germ cells are associated with histomorphometric variations, including those in the density of the structures that comprise the testicular parenchyma, and are more representative in bulls with poor semen quality. In addition, the unsatisfactory bulls for reproduction showed reduced meiotic potential compared to that of satisfactory reproductive bulls. Key words: Bovine, histopathology, testicular morphometry ResumoO objetivo neste estudo foi de avaliar aspectos morfológicos, morfométricos e funcionais da espermatogênese com base na condição reprodutiva seminal em touros Nelore. Foram utilizados 25 touros Bos indicus (Nelore), os quais foram classificados em aptos (n=10) e inaptos (n=15) à reprodução. Após orquiectomia, fragmentos do testículo direito de cada animal foram processados segundo técnicas de rotina e corados com Hematoxilina e Eosina (HE) e Ácido Periódico de Shiff (PAS). As lâminas foram analisadas em microscopia de campo claro em diferentes aumentos. Os segmentos tubulares foram classificados em quatro níveis (normal, degeneração leve e moderada, degeneração acentuada, e hipoplasia tubular) baseados na organização e arquitetura do tecido tubular. Foi obtida a média da altura do epitélio seminífero, da espessura da túnica própria e do diâmetro tubular dos segmentos e foi registrada a proporção de túbulo seminífero, tecido intersticial, vaso linfático e vaso sanguíneo dos testículos de cada touro. Além disso, quantificou-se a frequência das três classificações do ciclo espermatogênico A, B e C (A=agrupamento dos estágios I,II, e III que compreendem as fases in...

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

Cited by 184 publications

References 53 publications

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

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

Spermatogenesis in the Cynomolgus Monkey (Macaca fascicularis): A Practical Guide for Routine Morphological Staging

Histopathological and histomorphometric testicular characteristics associated to reproductive condition in Bos indicus (Nellore) bulls

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