Modulating role of pheromonal cues from oestrus-specific urine on 3-methylcholanthrene-induced male reproductive toxicity.

Polyaromatic hydrocarbons (PAHs) are persistent organic pollutants that contribute to endocrine/gonadal disruption. This study was designed to investigate the endocrine modulating role of pheromones in alleviating the reproductive toxic effects of 3-MC (3-methylcholanthrene), one of the common PAHs, in rat model. The rats were injected intraperitoneally with 3-MC at a dose of 25 mg kg(-1) BW. The serum levels of testosterone and other biochemical parameters were altered to significant levels in 3-MC-treated rats and oestrus-specific urine exposure restored all these effects to near normal. Although testis weight did not indicate any significant change, sperm and spermatid counts were significantly reduced in 3-MC-treated rats, which became normal in oestrus-urine-exposed rats. Hence, this study suggests that oestrus-specific urinary pheromones have the potential to modulate the endocrine system and alleviate the male reproductive toxic effects produced by 3-MC.

Spermidine may decrease ER stress in pancreatic beta cells and may reduce apoptosis via activating AMPK dependent autophagy pathway.

The risk for diabetes increases with increasing BMI<25. Insulin resistance is the key factor for type 2 diabetes; studies revealed that endoplasmic reticulum stress is the main factor behind this disease. With increase in ER stress, pancreatic beta cells start to undergo apoptosis, leading to a decline in the pancreatic beta cell population. The ER stress arises due to unfolded protein response. Recently, spermidine get importance for increasing the longevity in most of the eukaryotes including yeast, Caenorhabditis elegans, Drosophila and human peripheral blood mononuclear cells via induction of autophagy pathway. Autophagy is also involved in regulation of scavenging of proteins. One of the major cellular pathways for scavenging the aggregated intracellular protein is autophagy. Hence spermidine can be a candidate for the treatment type 2 diabetes. Autophagy genes are regulated by mTOR (mammalian Target Of Rapamycin) dependent or independent pathway via AMPK. Hence either inhibition of mTOR or activation of AMPK by spermidine will play two crucial roles, first being the activation of autophagy and secondly the reduction of endoplasmic reticulum stress which will reduce beta cell death by apoptosis and thus can be a novel therapeutic candidate in the treatment of insulin resistance in type 2 diabetes and preserving pancreatic beta cell mass.