~3 month-old male Fischer 344 rat

SIGNALMENT: (age, breed, sex, species, and scientific name) 

~3 month-old male Fischer 344 rat.

TREATMENT PROTOCOL (including test  compound):

Animals were treated once daily with 50 mg acrylamide/kg body weight by i.p. injection. All rats lost body weight within the first few days and developed varying severity of hind-limb paresis and ataxia. The acrylamide dose was reduced to 30 mg/kg after day 4, and injections were discontinued after day 8. Animals were killed on day 11 by an i.p. injection of pentobarbital and whole-body perfusion with buffered 4% paraformaldehyde via a cannula in the ascending aorta. Tissues were routinely processed, sectioned, and stained with hematoxylin and eosin (images are all from the same animal).  


GROSS PATHOLOGY:

Testes were small and pale. Epididymides were reddened.


LABORATORY RESULTS: (clinical pathology, microbiology, etc…)

None

MORPHOLOGIC DIAGNOSES: 

1. Testicular degeneration,
2. Multifocal cerebellar Purkinje and granular layer cell necrosis due to acrylamide toxicity.


CONTRIBUTOR'S COMMENTS:  

Acrylamide was used to induce lesions for positive-control neuropathology in accordance with the EPA’s Tier 2 regulations on toxicology of engine emissions from testing fuels and fuel additives (40 CFR, Part 79.66(e)(3)). Cerebellar lesions consisting of granular layer cell degeneration and Purkinje cell necrosis have been described previously in acrylamide-treated rats (Abou-Donia et al., 1993).

Short-term administration of acrylamide has been shown to selectively affect round spermatids in stages I-III in the mouse testis (Sakamoto et al., 1988), but published histopathology of testicular lesions in rats that have been induced by acrylamide or acrylamide derivatives is lacking. Analysis of specific lesions of reproductive toxicity in the rat was not the purpose of the current study. Aside from the generalized degeneration of seminiferous tubules depicted here, other acrylamide-intoxicated rats displayed testicular changes ranging from mild multifocal tubular degeneration to marked locally extensive necrosis and hemorrhage. A time-course and dose-response study would be necessary for a better understanding of the pathogenesis of these lesions.


REFERENCES:
Abou-Donia, M.B., Ibrahim, S.M., Corcoran, J.J., Lack, L., Friedman, M.A., Lapadula, D.M. (1993) Neurotoxicity of glycidamide, an acrylamide metabolite, following intraperitoneal injections in rats. J. Toxicol. Environ. Health 39:447-464.

Sakamoto, J., Kurosaka, Y., Hashimoto, K. (1988) Histological changes of acrylamide-induced testicular lesions in mice. Exp. Mol. Pathol.; 48(3): 324-334.

 

N001 brain 10x.jpg

10X H&E. Cerebellum from a rat treated with acrylamide. Note Purkinje cell hypereosinophilia and nuclear pyknosis. Vacuolar change, nuclear condensation, and pyknosis are present in cells of the granular layer.  

N001 brain 40x.jpg

40X H&E. Cerebellum from a rat treated with acrylamide. The higher magnification shows nuclear fragments scattered in the granular cell layer.

N001 testis 10x.jpg

10X H&E. Testis from a rat treated with acrylamide. Degeneration is characterized by the formation of luminal multinucleated cells.

N001 testis 40x.jpg

40X H&E. Testis from a rat treated with acrylamide. Higher magnification showing detail of tubular degeneration. 

1 Comment

multinucleated agreegates in seminiferous tubules

August 19, 2019 03:12 PM by Hibret A Adissu, DVM, DVSc, MSc, PhD, DACVP

Thank you for sharing this interesting case. The degree of multinucleate syncytium (symplast, multinucleate giant cell) is striking. I have noticed such level of multinucleated agree gates in a mouse line null for one of the Peroxisome  Biogenesis factors (PEX). Interestingly, similar morphology was documented in Pex-mutant Drosophila (Haiyang Chen et al. Hum. Mol. Genet. 2010;19:494-505). Not that this morphological feature is specific to any specific causation, I wonder if the underlying molecular mechanism involves perturbation of expression and/or function of the PEXs.

 

Some notes on multinucleated aggregates from Lanning et al., 2002, TOX. PATHOLOGY,  507–520): This morphology may signify a slow degenerative process leading to adjacent germ cells belonging to the same cohort forming a multinucleate syncytium (aka: symplast, multinucleate giant cell), probably due to the breakdown of the cytoskeletal fibers supporting the interconnecting cytoplasmic bridges. Multinucleate aggregates are less readily phagocytized by Sertoli cells and are present for longer periods and therefore more frequently seen. These structures are most frequently composed of round spermatids, but can also be formed by fusion of neighboring spermatocytes or elongating spermatids

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