Sex-specific differences of hepatic metabolism in Schistosoma mansoni infection

Questions Schistosomiasis is one of the most common parasitic infections of humans worldwide with at least 290 million people that required preventive treatment in 2018. During chronic infection, half to two thirds of the parasite´s eggs deposited in mesenteric venules of the mammalian host are swept into the liver. The aim of the study was to investigate gender-specific differences in the dysregulation of hepatic metabolism during Schistosoma mansoni infection.

Methods Key enzymes of hepatic metabolism were investigated in liver tissue samples of a hamster S. mansoni infection model. Male and female hamsters were either S. mansoni bisex-, single sex-, or non-infected. Liver samples were analyzed by western blotting and malondialdehyde assay (MDA).

Results While rate limiting enzymes of glycolysis were upregulated, gluconeogenesis, glycogenesis, pentose phosphate pathway, and fatty acid synthesis were reduced in S. mansoni-bisex-infected hamster livers of both gender without differences. Further, we observed increased oxidative stress in the livers of bisex-infected female hamsters compared to single-sex or non-infected hamsters whereas in male hamsters no group differences occurred. Markers of late hepatic autophagy were generally upregulated in bisex-infected female hamsters and downregulated in bisex-infected males compared to single-sex- or non-infected control groups.

Conclusion We demonstrated that S. mansoni-infection leads to a dysregulation of the carbohydrate and lipid metabolism in the liver of hamsters without gender-specific regulatory differences. However, S. mansoni induced oxidative stress in the liver of female hamsters but not in males. In line with these findings, we detected an upregulation of autophagy in females. It remains unclear, however, whether autophagy can excert a protective effect or instead contribute to the pathogenesis of schistosomiasis. For the development of novel therapeutic approaches and diagnosis of liver disease, it should be taken into consideration that autophagy could represent a key and critical factor in hepatic injury.

Publication History

Article published online:
04 January 2021