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Sex and strain differences in mouse kidney: Bowman's capsule morphology and susceptibility to chloroform
Abstract:
Chloroform (CHCl3) produces liver damage in male and female mice but renal injury only in male mice. Previous reports demonstrated that the parietal epithelium of Bowman's capsule in female mice is composed of squamous cells, whereas the parietal cells of Bowman's capsule from male mice consist of a mixture of squamous and cuboidal cells or purely cuboidal cells. These data suggested that the factor(s) associated with these histological differences may similarly be associated with factors that determine susceptibility to tubular damage from chloroform. The susceptibility of male mice to chloroform nephrotoxicity varies with animal strain. In the present study, administration of CHCl3 to male C57BL/6J (C57) and male and female DBA/2J (DBA) mice produced dose-dependent kidney tubular damage in male C57 and male DBA mice. However, CHCl3 nephrotoxicity was considerably greater in male DBA mice than in male C57 mice. Female DBA mice failed to develop renal damage following administration of CHCl3. Male DBA mice had a higher percentage of cuboidal parietal epithelial cells in Bowman's capsule whereas male C57 mice had a higher percentage of squamous cells in the parietal epithelium. The parietal epithelium in Bowman's capsule of female DBA mice was predominantly squamous. Since morphological differences between sex and strain of mice occurred in the capsular epithelium, and the differences in susceptibility to CHCl3 appear to be a tubular phenomenon, it is unlikely that there is a causal relationship between the structure of Bowman's capsule and chloroform-induced renal tubular necrosis; rather, these two independent phenomena are regulated by some common factor(s), possibly testosterone.
Insights
Chloroform causes liver damage in all mice, but only male mice develop kidney injury. Differences in kidney susceptibility to chloroform toxicity are linked to common factors, potentially testosterone.
Area of Science:
- Toxicology
- Nephrology
- Histology
Background:
- Chloroform (CHCl3) induces liver damage in both male and female mice.
- Renal injury from chloroform is observed exclusively in male mice.
- Histological differences in Bowman's capsule parietal epithelium exist between male and female mice.
Purpose of the Study:
- To investigate the strain- and sex-dependent susceptibility of mice to chloroform-induced nephrotoxicity.
- To explore the potential relationship between kidney tubule damage and the morphological characteristics of Bowman's capsule epithelium.
- To identify potential regulatory factors, such as testosterone, influencing chloroform nephrotoxicity.
Main Methods:
- Administration of varying doses of chloroform (CHCl3) to male C57BL/6J (C57) and male and female DBA/2J (DBA) mice.
- Assessment of dose-dependent kidney tubular damage.
- Histological examination of Bowman's capsule parietal epithelium in different mouse groups.
Main Results:
- Male C57 and male DBA mice exhibited dose-dependent kidney tubular damage following chloroform administration.
- CHCl3 nephrotoxicity was significantly greater in male DBA mice compared to male C57 mice.
- Female DBA mice did not develop renal damage after chloroform exposure.
- Male DBA mice showed a higher proportion of cuboidal parietal epithelial cells, while male C57 mice had more squamous cells.
- Female DBA mice predominantly displayed squamous parietal epithelial cells.
Conclusions:
- The observed morphological differences in Bowman's capsule epithelium between sexes and strains are unlikely to be causally related to chloroform-induced renal tubular necrosis.
- Susceptibility to chloroform nephrotoxicity appears to be a tubular phenomenon, independent of Bowman's capsule structure.
- Common regulatory factors, possibly testosterone, may influence both the epithelial morphology and the susceptibility to renal tubular damage from chloroform.