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

Abstract

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.

Metabolic Network Models of the Gardnerella Pangenome Identify Key Interactions with the Vaginal Environment

“…These findings suggest that some strains of Gardnerella may sequester mannose-6-phosphate as a mechanism of evading host lysosomal clearance. This phenotype would result in disordered vaginal epithelial cell function due to the lack of waste removal and would likely be concordant with increased inflammation and oxidative stress ( 43 , 44 ).…”

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

“…In other lysosomal storage diseases, a region-specific effect was noted for hexosaminidase Hexa -/- (Hex A-deficient) mice, whereas in Hexb -/- (Hex B-deficient) mice, principal cells of all regions were grossly affected as were clear and narrow cells. Details on adverse effects on the male reproductive system in the case of lysosomal storage diseases can be found in Vuolo et al [ 103 ].…”

Metabolic network models ofGardnerellapangenome identify interactions in the vaginal environment

“…These findings suggest that some strains of Gardnerella may sequester mannose-6-phosphate as a mechanism of evading host lysosomal clearance. This phenotype would result in disordered vaginal epithelial cell function, due to lack of waste removal and would likely be concordant with increased inflammation and oxidative stress (Ferreira and Gahl, 2022; Vuolo et al, 2021).…”