Genetic susceptibility against environmental fators on male infertility

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Male reproductive function is impaired by various environmental factors such as smoking, heat stress, endocrine-disrupting chemicals and oxidative stresses. There are inter-individual variability of xenobiotic metabolism, and genetic polymorphisms modulate susceptibility to male infertility associated with environmental factors. Polymorphisms of glutathione S-transferase (GST) M1/T1, key enzymes in the extrahepatic metabolism of xenobiotics, have been shown to influence susceptibility to male infertility associated with xenobiotics including smoking. First, the association between smoking and GSTTI/M1 polymorphisms were investigated in 194 infertile Japanese men. Of the 145 patients with non-obstructive male infertility, 85(58.6%) men had GSTM1 null genotype. Control population and infertile patients with normal spermatogenesis had GSTM1 null genotype in 52.2% and 55.1%. In contrast, the frequencies of GSTT1(+) is not significantly different between non-obstructive male infertility and … More control. Of non-obstructive male infertility, patients with varicocele had higher frequency of GSTM1 null genotype than control. These preliminary results suggest that the GSTM1 null genotype may be associated with individual susceptibility to male infertility associated with varicocele. Secondly, to investigate the effect of oxidative stress and heat stress on male infertility, we examined experimentally induced cryptorchid testes in thioredoxin transgenic mice, which have cytoprotective effects against various types of oxidative stresses. Unilateral cryptorchidism was surgically induced both in TRX transgenic (TRX-tg) and wild type adult mice, and testicular damage was evaluated by measuring testis weight and analyzing tcsticular histology. Weight reduction of cryptorchid testis was significantly decreased in TRX-tg mice, compared with those in wild type mice. Moreover, testicular histology and TUNEL staining demonstrated that apoptotic changes were delayed by 4 days in TRX-tg mice compared with those in WT mice. These results suggest that oxidative stress is associated with male infertility and polymorphisms of oxidative stress-related genes may be associated with individual susceptibility to male infertility induced by environmental factors Less