Abstract
Abstract
Diabetes-induced hyperglycemia has previously been shown to impact on male sub-/infertility, however, still little is known about the underlying mechanisms. In the present study we have addressed three major biochemical pathways implicated in the pathogenesis of hyperglycemia induced organ damage (the advanced glycation end product (AGE) formation pathway, the diacylglycerol-protein kinase C pathway (PKC), and the polyol pathway) in both testis and epididymis of the Ins2Akita mouse model of Type 1 diabetes (T1DM). Hyperglycemia activated both the PKC and the polyol pathway in a significant and progressive manner within the testis, but not within the epididymis. While the AGE receptor was ubiquitiously expressed in the testis, concentrations of precursor methylglyoxal and AGE carboxymethyllysine were increased in both epididymis and testis in diabetic mice. However, AGEs did not activate intracellular pathways of ERK1, ERK2, Rela, Nrf-2, IkBkB, NFkB except CDC42, Akt1. In conclusion, two of the major pathways of hyperglycemia-induced organ damage were clearly activated within the testis of T1DM mice. This provides therapeutical opportunities in the treatment of diabetic male reproductive dysfunction.
Funder
Deutsche Forschungsgemeinschaft
Publisher
Springer Science and Business Media LLC
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