Abstract
At present, one of the main threats to humanity is undoubtedly endocrine disruptors (ED), since they directly disrupt the processes of ensuring homeostasis, which are identical to the very essence of the concept of health, considered in valeology as the ability to maintain age-appropriate stability in conditions of sharp changes in quantitative and qualitative parameters of the triune flow of sensory, verbal and structural information. Pesticides can disrupt the physiological functioning of many endocrine chains, including the endocrine mechanisms that ensure reproductive health. The study aimed to compare the results of our studies of alpha-cypermethrin reproductive toxicity in the test system for studying gonadotoxic activity with data obtained in the test system "Three Generation Reproduction Study". The studies were performed on male and female Wistar Han rats with two generic samples of alpha-cypermethrin from different manufacturers at doses of 0.2, 1.0 and 3.0 mg/kg body weight. The exposure lasted 11 (males) and 10 (females) weeks. During the last two weeks of exposure the state of the estrous cycle, duration and frequency of each stage in females was studied. After the end of treatment functional parameters of the state of the gonads in males and the ability of animals to reproduce were examined. In males, the total sperm count, the absolute and relative number of motile germ cells, and the number of pathologically altered forms were evaluated. The results of the study showed that exposure of male and female Wistar Han rats to alpha-cypermethrin at doses of 0.2–3.0 mg/kg during gametogenesis had a toxic effect on the reproductive system characterized by impaired gonadal and reproductive functions. In our studies, alpha-cypermethrin was found to have reproductive toxicity (reduced number of corpora luteum and live fetuses, increased absolute and relative postimplantation death, reduced average weight of fetuses and litters) and endocrine-disruptive effect, having a pronounced antiandrogenic effect on males. Obvious signs of endocrine reproductive disorders (changes in testis and epididymis weight, deterioration in semen parameters, altered length of separate stages of the estrous cycle) were observed in both females and males. However, studies in a test system of three-generations did not reveal a reproductive and endocrine-disruptive effect of cypermethrin, the toxicity of which was recognized as equivalent to the toxicity of alpha-cypermethrin. The obtained results showed higher sensitivity, informative and diagnostic significance of the methods for studying gonadotoxicity than the methodology of reproductive toxicity studies in the test system “Three Generation Reproduction Study”.
Highlights
At present, one of the main threats to humanity is undoubtedly endocrine disruptors (ED), since they directly disrupt the processes of ensuring homeostasis, which are identical to the very essence of the concept of health, considered in valeology as “the ability to maintain age-appropriate stability in conditions of sharp changes in quantitative and qualitative parameters of the triune flow of sensory, verbal and structural information” (Brekhman, 1990)
For a comparative evaluation of diagnostic value and sensitivity of the approaches under consideration, we have presented the results of our study of the gonadotoxic activity of two samples of alphacypermethrin (AC1 and AC2) and the results of study of reproductive toxicity of this xenobiotic in “Three Generation Reproduction Study”
The registration of body weight in treated and control male and female animals during the experimental period demonstrated that AC1 and AC2 did not affect the dynamics of body weight among treated animals
Summary
One of the main threats to humanity is undoubtedly endocrine disruptors (ED), since they directly disrupt the processes of ensuring homeostasis, which are identical to the very essence of the concept of health, considered in valeology as “the ability to maintain age-appropriate stability in conditions of sharp changes in quantitative and qualitative parameters of the triune flow of sensory, verbal and structural information” (Brekhman, 1990). Pesticides can disrupt the physiological functioning of many endocrine chains, including the endocrine mechanisms that ensure reproductive health. An understanding of the need to develop methodological approaches to examine possible violations of reproductive function under the influence of xenobiotics entering the human body through food, water, air throughout life, developed in the 1950s. As a result of long discussions (Barnes & Denz, 1954; Lehman, 1958) and debates, the methodological test “Three Generation Reproduction Study” was proposed (Lenz, 1958; Fitzhugh, 1968; Fishbein, 1970). According to the proposed experimental scheme, testing of chemical compounds provided for the study of reproductive function of at least three generations and 9 litters (3 litters in each generation). Despite the fact that for a long time this methodological approach was used by all the leading scientific centers of the world, the problem of optimizing the experimental design remained the subject of extensive scientific discussion (Delahunt & Lassen, 1964; Раlmer, 1978; Раlmer, 1981), which eventually led to a significant revision of the original experimental design
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