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Dichlorodiphenyltrichloroethane (DDT) is the most widespread, persistent pollutant and endocrine disruptor on the planet. Although DDT has been found to block androgen receptors, the effects of its low-dose exposure in different periods of ontogeny on the male reproductive system remain unclear. We evaluate sex steroid hormone production in the pubertal period and after maturation in male Wistar rats exposed to low doses of o,p’-DDT, either during prenatal and postnatal development or postnatal development alone. Prenatally and postnatally exposed rats exhibit lower testosterone production and increased estradiol and estriol serum levels after maturation, associated with the delayed growth of gonads. Postnatally exposed rats demonstrate accelerated growth of gonads and higher testosterone production in the pubertal period. In contrast to the previous group, they do not present raised estradiol production. All of the exposed animals exhibit a reduced conversion of progesterone to 17OH-progesterone after sexual maturation, which indicates putative attenuation of sex steroid production. Thus, the study reveals age-dependent outcomes of low-dose exposure to DDT. Prenatal onset of exposure results in the later onset of androgen production and the enhanced conversion of androgens to estrogens after puberty, while postnatal exposure induces the earlier onset of androgen secretion.

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Objective ― impact of different time regimens of deuterium depletion on progression of syngeneic grafted tumor in mice was investigated. Material and Methods ― Experiment was performed on 64 C57Bl/6 mice divided into two groups with substitution of regular water for deuterium depleted water: 30 days prior to tumor cell inoculation and sinse the 1st day of inoculation. Mice taking destilled mineralized water were considered as a control group. Half of the mice were injected melanoma B16 cells subcutaneously for assessment of survival rate and tumor growth inhibition index. The other mice were intravenously injected melanoma cells for estimation of lung hematogenous metastasis. Results ― Deuterium depletion began at the day of tumor inoculation did not change the parameters of survival rate (38.83±7.69 days vs. 41.33±6.22days in the control). Tumor growth inhibition was found only at initial stage of tumor progression. Number of melanoma lung metastasis did not differ from the control values (32.30±6.12 and 28.33±5.38. consequently). The group of mice with preliminary consumption of deuterium depleted water demonstrated significantly higher survival rate (70.10±16.20 days), tumor inhibition index, and attenuation of lung metastasis (6.0±1.20). Conclusion ― Our findings demonstrate that deuterium depletion exerts antitumor effect by both inhibition of tumor growth and metastasis, but development of the effect is time-dependent.

Objective -The study is focused on the secretion of adrenal zona glomerulosa cells in rats exposed to low doses of dichlorodiphenyltrichloroethane (DDT) during prenatal and postnatal development. Material and Methods -Experiment was carried out on male Wistar rats exposed to low dose of DDT during prenatal and postnatal development. Aldosterone serum levels, zona glomerulosa histology and fine structure of glomerulosa cells were examined in pubertal and adult rats. Results -Rats exposed to low doses of DDT during prenatal and postnatal development showed lower aldosterone serum levels in puberty and restoration of aldosterone secretion after puberty. Histological examination revealed retardation of zona glomerulosa development and circulatory disorders in pubertal rats. Electron microscopy revealed typical signs of decreased steroidogenic activity of glomerulosa cells. After puberty DDT-exposed rats exhibited hyperplasia of zona glomerulosa and less pronounced changes in number and structure of mitochondria. Conclusion -Developmental exposure to low doses of DDT resulted in dysmorphogenesis of zona glomerulosa and, therefore, in impaired aldosterone secretion in puberty. Restoration of normal secretion of aldosterone after puberty was achieved by hyperplasia of zona glomerulosa.

Sex differences in the expression of iodide transporter SLC5A5 and thyroid peroxidase in thyroid follicular epithelium and thyroid serum profile were assessed in pubertal rats exposed to endocrine disruptor DDT starting from the first postnatal day. It was found that exposure to DDT reduced expression of SLC5A5 in peripheral regions of thyroid lobes in males and in central regions in females. The most pronounced sex differences were observed in thyroid peroxidase expression that remained sensitive to thyroid stimulating hormone regulation in males and lost sensitivity to pituitary stimulation in females after exposure to disruptor, which determines more pronounced hypothyroidism in females.

Transcription factor PRH/Hhex suppresses cell proliferation and contributes to regulation of prenatal and postnatal ontogeny. Neurons of the peripheral nervous system and chromaffin cells were previously considered as non-expressing PRH/Hhex in postnatal development. In our study, the expression of PRH/Hhex in chromaffin cells of rat adrenal glands and association between the decrease of proliferation and activation of PRH/Hhex expression were demonstrated.