A mixture of pyrethroids induces reduced fecundity and increased testicular genotoxicity in rats.

To achieve crop protection and higher agricultural yield, pesticides are used; and among them pyrethroid based ones are the most preferred choice because of their specificity on the pests. Uncontrolled use of pesticides resulted in contamination of food products. Presence of residual amounts of pyrethroids was reported in agricultural products sold in Indian market, indicating that humans are constantly exposed to these chemicals through food on a routine basis. Studies that determine the toxic effects of pyrethroids at doses equivalent to human exposure are rare. We orally administered a mixture of pyrethroids (detected in the rice and vegetables of Indian market) to male rats for 15 months to mimic the long-term exposure in humans. We observed reduced fecundity, sperm count and 13ß-hydroxysteroid dehydrogenase enzyme activity. The serum concentrations of hormones involved in male reproductive function were altered. Further, testicular genotoxicity as reflected by perturbations in the expression pattern of genes involved in the molecular processes of gametogenesis was evident. Such toxic effects may also be occurring in humans who consume agricultural products that contain residual amounts of pyrethroids on a regular basis throughout their lifetime.

Transgenerational effects on the fecundity and sperm proteome in rats exposed to a mixture of pyrethroids at doses similar to human consumption.

Pyrethroid based pesticide usage for crop protection resulted in percolation of these compounds into the food chain. Toxicological studies that reflect exposure to pyrethroids through food in the human settings are rare. We conducted animal experimentations using a mixture of pyrethroids that is equivalent to the amount consumed by average individual through rice and vegetables in the Indian context. Male rats treated with a mixture of pyrethroids for 1-12 months displayed decreased transgenerational fecundity, sperm count, activities of 3ß- and 17ß-HSD and perturbed hormonal profile. At the transcriptome level, the expression of genes involved in spermatogenesis, steroidogenesis, germ cell epigenetic modulators and germ cell apoptosis were altered in the testis. In the sperm lysates of control rats, 506 proteins identified by mass spectrometry. The differential expression of these proteins (treated/control ratio) in the pyrethroid exposed rats was analyzed. Among the 506 proteins, 153 had a ratio of 0; 41 had a ratio ranging from >0 to <0.5; and 10 had a ratio >2.0. Interestingly, the differential expression was transgenerational. 26 proteins that were differentially expressed in the sperm of F0 treated rats continued to remain the same in the F1, F2 and F3 generations, while the differential expression was maintained up to F2 and F1 generations for 46 and 2 proteins respectively. Some of the proteins that continued to be differentially expressed in the later generations are reported to have critical roles in male reproduction. These results indicate that the reduced fecundity observed in the later generations could be due to the continued differential expression that was initiated by pyrethroid treatment in the F0 rats. Results of our study, for the first time, provide evidence that long-term exposure to pyrethroids affects transgenerational fecundity manifested by changes in sperm proteome.

Pyrethroid based pesticides - chemical and biological aspects.

Human and animal welfare primarily depends on the availability of food and surrounding environment. Over a century and half, the quest to identify agents that can enhance food production and protection from vector borne diseases resulted in the identification and use of a variety of pesticides, of which the pyrethroid based ones emerged as the best choice. Pesticides while improved the quality of life, on the other hand caused enormous health risks. Because of their percolation into drinking water and food chain and usage in domestic settings, humans unintentionally get exposed to the pesticides on a daily basis. The health hazards of almost all known pesticides at a variety of doses and exposure times are reported. This review provides a comprehensive summation on the historical, epidemiological, chemical and biological (physiological, biochemical and molecular) aspects of pyrethroid based insecticides. An overview of the available knowledge suggests that the synthetic pyrethroids vary in their chemical and toxic nature and pose health hazards that range from simple nausea to cancers. Despite large number of reports, studies that focused on identifying the health hazards using doses that are equivalent or relevant to human exposure are lacking. It is high time such studies are conducted to provide concrete evidence on the hazards of consuming pesticide contaminated food. Policy decisions to decrease the residual levels of pesticides in agricultural products and also to encourage organic farming is suggested.

Effect of oral administration of a mixture of pyrethroids at doses relevant to human exposure on the general and male reproductive physiology in the rat.

Studies on the effects of unintentional intake of pyrethroid pesticides that are akin to actual human exposure settings are very rare. Such an exposure is primarily by consuming the food products as routine diet that contain residual levels of pyrethroids. In this study, rats were orally administered for 15 months with a mixture of pyrethroids at a dose that is one-fifth (high dose; HD) or one-twenty fifth (low dose; LD) of the residual levels commonly present in the average amount of rice and vegetables consumed by Indian population. Lipid profile, kidney and liver function were assessed. Lipid peroxidation, nitric oxide, antioxidant enzyme activities and histopathological changes were analyzed in the liver, lung, kidney, pancreas, testes, caput, cauda and prostate. The effect on the male reproductive system as a function of sperm count, enzyme activity of 3ß-HSD and 17ß-HSD and the expression profile of genes involved in spermatogenesis, steroidogenesis, genetic reprogramming and apoptosis of male gametes were evaluated. Significant increase in the relative organ weight, perturbations in the activities of antioxidant enzymes, lipid profile and liver function were observed in both LD and HD groups. Damage to the anatomical architecture was evident in all the tissues due to pyrethroid toxicity. Exposure to LD and HD of pyrethroid mixture resulted in decreased sperm count, activities of 3ß-HSD and 17ß-HSD, impaired capacitation and acrosome reaction and perturbations in the expression of genes that govern male gamete production. Results of our study indicate that exposure to pyrethroids for longer durations even at doses that are far below the residual levels present in the food consumed will result in severe damage to general physiological processes as well as reproductive function.

Long term oral administration of a mixture of pyrethroids affects reproductive function in rats.

Pyrethroid toxicity using dosages that are relevant to the human settings are not reported. Male Wistar rats were treated for 9 or 12 months daily with a mixture of pyrethroids equivalent to a fifth or a twenty-fifth of that is present in cereals and vegetables consumed by an average Indian adult. Altered oxidant and antioxidant status, severe anatomical damage in the testis, caput, cauda, prostate, liver, lung and kidney and increased serum SGPT, SGOT and ALP activity was evident in all the treatment groups. Decreased levels of 3ß- and 17ß-HSD activity, litter size and impaired acrosome reaction was observed in all the treatment groups. To the best of our knowledge, for the first time, we demonstrate that exposure to even very low levels of pyrethroids (relevant to human consumption) for longer durations could cause damage to tissues that are important in general and male reproductive physiology.

Evaluation of the reproductive toxicity of antiretroviral drug loaded lactoferrin nanoparticles.

Multiple prevention therapy has gained importance for the prevention and treatment of sexually transmitted diseases, especially HIV/AIDS. Antiretroviral drugs encapsulated in nanoparticles have been developed for efficient delivery of the drugs to the vaginal surface. Lactoferrin nanoparticles (LFNPs) encapsulating anticancer or antiretroviral drugs are found to be promising agents to specifically deliver drugs at the target sites. Recent studies indicate that the bioavailability is higher for antiretroviral drugs delivered by LFNPs than when the drugs are administered alone. Although LFNP-mediated drug delivery via the oral or vaginal route for the treatment of HIV/AIDS is promising, the effect of such administrations is not well studied. Drug-loaded LFNPs when administered to rats by the vaginal route did not show any effect on the reproductive performance, fertility, and postnatal development. Oral administration of drug-loaded LFNPs caused a significant decrease in litter size, whereas the reproductive performance and postnatal development remained normal. In our model system, the results indicate that vaginal administration of drug-loaded LFNPs appears safer and can be projected for the delivery of antiretroviral agents via the vaginal route. Abbreviations: LFNPs: lactoferrin nanoparticles; STIs: sexually transmitted diseases infections; NPs: nanoparticles; LF: lactoferrin; DL-LFNPs: drug loaded lactoferrin nanoparticles; MPT: multiple prevention techniques.