Hypobaric hypoxia is of interest due to an increase of human populations working at high altitude. Testicular damage is related to the physiological response (neoangiogenesis) to increased intrascrotal blood fl ow as temperature rises. Hypoxia is a stress factor with overproduction of reactive oxygen species (ROS). The effect of hypoxia in mice reproductive parameters is analyzed. Animals were exposed to simulated hypoxia of 4,200 meters above sea level (m.a.s.l.) in a chamber for 33.2 days, both to continuous (HH) or intermittent hypoxia (HI) with an intermittency period of 4 days hypoxia /4 days normoxia (500 m.a.s.l.). The anti-infl ammatory drug Ibuprofen was administered to a group of mice to control vasodilation and increased blood fl ow. Melatonin was administered to another group of mice as a potent ROS scavenger. Animals in both HH and HI exposure were compared to normoxic nontreated controls. There was a hematological response in hypoxia, with an increase in hematocrit and reticulocytosis. There was also increased teratozoospermia. This damage was more pronounced in HH than HI, suggesting that alternating normoxic periods permits compensation for the effects of hypoxia. In both hypoxia systems, the level of lipoperoxidation and the instability of DNA increased. In HH, there was a reduction of teratozoospermia in melatonin-treated mice. Ibuprofen presented a protective effect on the same parameters as melatonin with both HI and HH. The quality of sperm DNA, fragmentation, unpacking and DNA stability diminished. In conclusion, reproductive damage elicited by HH or HI was partially ameliorated by simultaneous treatment with antifl ogistic and/or antioxidant agents.

Inositol 1,4,5-trisphosphate (IP(3)) receptors (IP(3)Rs) drive calcium signals involved in skeletal muscle excitation-transcription coupling and plasticity; IP(3)R subtype distribution and downstream events evoked by their activation have not been studied in human muscle nor has their possible alteration in Duchenne muscular dystrophy (DMD). We studied the expression and localization of IP(3)R subtypes in normal and DMD human muscle and in normal (RCMH) and dystrophic (RCDMD) human muscle cell lines. In normal muscle, both type 1 IP(3)Rs (IP(3)R1) and type 2 IP(3)Rs (IP(3)R2) show a higher expression in type II fibers, whereas type 3 IP(3)Rs (IP(3)R3) show uniform distribution. In DMD biopsies, all fibers display a homogeneous IP(3)R2 label, whereas 24 +/- 7% of type II fibers have lost the IP(3)R1 label. RCDMD cells show 5-fold overexpression of IP(3)R2 and down-regulation of IP(3)R3 compared with RCMH cells. A tetanic stimulus induces IP(3)-dependent slow Ca(2+) transients significantly larger and faster in RCDMD cells than in RCMH cells as well as significant ERK1/2 phosphorylation in normal but not in dystrophic cells. Excitation-driven gene expression was different among cell lines; 44 common genes were repressed in RCMH cells and expressed in RCDMD cells or vice versa. IP(3)-dependent Ca(2+) release may play a significant role in DMD pathophysiology.

At present it is not clear if male fertility is affected by intermittent hypobaric hypoxia (IHH). This is an important issue since a large human population works over 3000 masl. This study analyzes epididymal sperm, in adult Sprague Dawley rats after five cycles of IHH (7 days exposure to 4200 masl in a hypobaric chamber / 7 days at 500 masl). The animals were separated into groups of 8, one group was exposed to hypoxia (7 days), and the others to IHH for one to five cycles. Controls (500 masl) were examined at the beginning and at the end of the 70 experimental days. A duplicate set of rats treated with melatonin (supposedly protecting from hypoxia) was also examined, as were their controls, injected with 0,03% ethanol (melatonin solvent). Epididymal sperm parameters, were evaluated. Damage caused by IHH increases with time. Sperm counts drop, while sperm chromatin swelling, DNA instability (metachromasia with acridine orange epifluorescence) and comet (+) tests increase. Melatonin counteracts all this damage, possibly due to its high efficiency as a reactive oxygen species scavenger. In conclusion, IHH exposure damages sperm quality and therefore male reproductive function.

This review briefly considers the testicular damage elicited by environmental chemical pollution. It includes a short comment on environmental toxicology as an introduction to environmental chemical pollution, highlighting the importance of this current field of study and its impact on male reproductive health. Furthermore an experimental animal model addressing the effect of organophosphorated agropesticides as a testicular toxicant is presented. Moreover two relevant chemical contaminants and their effect on the testis, such as the classical case of lead and the rarely reported case of Boron on spermatogenesis, are considered. Additionally, the subject of biosentinel species and their relevance for the monitoring of pollution in aquatic and/or terrestrial ecosystems is considered. In conclusion, it should be stressed that environmental health is closely related to the reproductive health of all living beings.