Morphological damage in Sertoli, myoid and interstitial cells in a mouse model of mucopolysaccharidosis type I (MPS I)

Nascimento, Cinthia Castro do; Aguiar, Odair; Viana, Gustavo Monteiro; D’Almeida, Vânia

doi:10.1007/s11033-020-06055-5

Cited by 2 publications

(2 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The phenotype observed in MPS IIIC cells can be compared with mucopolysaccharidosis type I (MPS I), a lysosomal storage disease caused by a mutation in the Idua gene, which codes α-L-iduronidase (IDUA). In Idua -/- mouse model, Nascimento et al [ 94 ] detected abnormalities in Sertoli cells suggestive of incomplete digestion of substrates since vesicles similar to autophagosomes, autolysosomes and lysosomes were detected in a different proportion as seen in wild type mice [ 95 ]. In arylsulfatase A KO mice, sulfogalactosylglycerolipid, a major sulfoglycolipid of male germ cells, accumulated in Sertoli cells at 8 months with buildup seen as lysosomal swelling and other cellular abnormalities typical of a lysosomal storage disorder [ 91 ].…”

Section: Discussionmentioning

confidence: 99%

“…abnormalities in Sertoli cells suggestive of incomplete digestion of substrates since vesicles similar to autophagosomes, autolysosomes and lysosomes were detected in a different proportion as seen in wild type mice [95]. In arylsulfatase A KO mice, sulfogalactosylglycerolipid, a major sulfoglycolipid of male germ cells, accumulated in Sertoli cells at 8 months with buildup seen as lysosomal swelling and other cellular abnormalities typical of a lysosomal storage disorder [91].…”

Section: Plos Onementioning

confidence: 91%

See 1 more Smart Citation

Effects of Heparan sulfate acetyl-CoA: Alpha-glucosaminide N-acetyltransferase (HGSNAT) inactivation on the structure and function of epithelial and immune cells of the testis and epididymis and sperm parameters in adult mice

Carvelli,

Hermo,

O’Flaherty

et al. 2023

PLoS ONE

View full text Add to dashboard Cite

Heparan sulfate (HS), an abundant component of the apical cell surface and basement membrane, belongs to the glycosaminoglycan family of carbohydrates covalently linked to proteins called heparan sulfate proteoglycans. After endocytosis, HS is degraded in the lysosome by several enzymes, including heparan-alpha-glucosaminide N-acetyltransferase (HGSNAT), and in its absence causes Mucopolysaccharidosis III type C (Sanfilippo type C). Since endocytosis occurs in epithelial cells of the testis and epididymis, we examined the morphological effects of Hgsnat inactivation in these organs. In the testis, Hgsnat knockout (Hgsnat-Geo) mice revealed statistically significant decrease in tubule and epithelial profile area of seminiferous tubules. Electron microscopy (EM) analysis revealed cross-sectional tubule profiles with normal and moderately to severely altered appearances. Abnormalities in Sertoli cells and blood-testis barrier and the absence of germ cells in some tubules were noted along with altered morphology of sperm, sperm motility parameters and a reduction in fertilization rates in vitro. Along with quantitatively increased epithelial and tubular profile areas in the epididymis, EM demonstrated significant accumulations of electrolucent lysosomes in the caput-cauda regions that were reactive for cathepsin D and prosaposin antibodies. Lysosomes with similar storage materials were also found in basal, clear and myoid cells. In the mid/basal region of the epithelium of caput-cauda regions of KO mice, large vacuolated cells, unreactive for cytokeratin 5, a basal cell marker, were identified morphologically as epididymal mononuclear phagocytes (eMPs). The cytoplasm of the eMPs was occupied by a gigantic lysosome suggesting an active role of these cells in removing debris from the epithelium. Some eMPs were found in proximity to T-lymphocytes, a feature of dendritic cells. Taken together, our results reveal that upon Hgsnat inactivation, morphological alterations occur to the testis affecting sperm morphology and motility parameters and abnormal lysosomes in epididymal epithelial cells, indicative of a lysosomal storage disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Plos Onementioning

confidence: 91%

Effects of Heparan sulfate acetyl-CoA: Alpha-glucosaminide N-acetyltransferase (HGSNAT) inactivation on the structure and function of epithelial and immune cells of the testis and epididymis and sperm parameters in adult mice

Carvelli,

Hermo,

O’Flaherty

et al. 2023

PLoS ONE

View full text Add to dashboard Cite

show abstract

Reproduction in Animal Models of Lysosomal Storage Diseases: A Scoping Review

Vuolo

Nascimento

D’Almeida

2021

Front. Mol. Biosci.

Self Cite

View full text Add to dashboard Cite

Background: Lysosomal storage diseases (LSDs) are caused by a mutation in a specific gene. Enzymatic dysfunction results in a progressive storage of substrates that gradually affects lysosomal, cellular and tissue physiology. Their pathophysiological consequences vary according to the nature of the stored substrate, making LSDs complex and multisystemic diseases. Some LSDs result in near normal life expectancies, and advances in treatments mean that more people reach the age to have children, so considering the effects of LSDs on fertility and the risks associated with having children is of growing importance.Objectives: As there is a lack of clinical studies describing the effect of LSDs on the physiology of reproductivity, we undertook a scoping review of studies using animal models of LSDs focusing on reproductive parameters.Methods: We searched six databases: MEDLINE, LILACS, Scopus, Web of Science, Embase and SciELO, and identified 49 articles that met our inclusion criteria.Results: The majority of the studies used male animal models, and a number reported severe morphological and physiological damage in gametes and gonads in models of sphingolipidoses. Models of other LSDs, such as mucopolysaccharidoses, presented important morphological damage.Conclusion: Many of the models found alterations in reproductive systems. Any signs of subfertility or morphological damage in animal models are important, particularly in rodents which are extremely fertile, and may have implications for individuals with LSDs. We suggest the use of more female animal models to better understand the physiopathology of the diseases, and the use of clinical case studies to further explore the risks of individuals with LSDs having children.

show abstract

Morphological damage in Sertoli, myoid and interstitial cells in a mouse model of mucopolysaccharidosis type I (MPS I)

Cited by 2 publications

References 38 publications

Effects of Heparan sulfate acetyl-CoA: Alpha-glucosaminide N-acetyltransferase (HGSNAT) inactivation on the structure and function of epithelial and immune cells of the testis and epididymis and sperm parameters in adult mice

Effects of Heparan sulfate acetyl-CoA: Alpha-glucosaminide N-acetyltransferase (HGSNAT) inactivation on the structure and function of epithelial and immune cells of the testis and epididymis and sperm parameters in adult mice

Reproduction in Animal Models of Lysosomal Storage Diseases: A Scoping Review

Contact Info

Product

Resources

About