Morphological and Cytophysiological Changes in the Adult Rat Adrenal Medulla after Prenatal and Postnatal Exposure to Endocrine-Disrupting DDT

The aim of the investigation was to study morphological and cytophysiological changes in the adult rat adrenal medulla after prenatal and postnatal exposure to endocrine-disrupting chemical dichlorodiphenyltrichloroethane (DDT).

Materials and Methods. The experiment was carried out on male Wistar rats (n=30). The rats were exposed to low doses of DDT during prenatal and postnatal development (n=10) and during postnatal development (n=10) only. The average daily intake of DDT by rats was 3.30±0.14 μg/kg. The control (n=10) and experimental animals were sacrificed at the age of 10 weeks (post-puberty), when rat adrenal glands reached their maximum development. Histological samples of the equatorial sections of the adrenal glands were prepared. The adrenal medulla was studied using light microscopy and computer morphometry. Immunohistochemistry was performed to evaluate tyrosine hydroxylase expression in chromaffin cells. Plasma epinephrine content was measured using enzyme-linked immunosorbent assay.

Results. Postnatal exposure of rats to low doses of the endocrine disruptor was found to interfere with adrenal medulla development and cytophysiology of chromaffin cells. Prenatal and postnatal exposure resulted in more profound delay in adrenal medulla development of adult rats as compared to the values of rats exposed postnatally, which was manifested by reduced area of the adrenal medulla and reduced total area of chromaffin cells in its section. Postnatal exposure is manifested by more significant functional disorders including decreased synthesis of tyrosine hydroxylase enzyme in the cytoplasm of chromaffin cells and elevated number of tyrosine-hydroxylase-negative cells in the medulla section, leading to a decrease in plasma epinephrine concentration.

Conclusion. Exposure to low doses of DDT in the early stages of development leads to morphological and cytophysiological changes in the adult rat adrenal medulla and, therefore, reduced functional activity of chromaffin cells, which allows considering the endocrine disruptor DDT a potential risk factor disrupting the function of the neuroendocrine system.

1. Yaglova N.V., Yaglov V.V. Endocrine disruptors are a novel direction of endocrinologic scientific investigation. Vestnik Rossijskoj akademii medicinskih nauk 2012; 67(3): 56–61, https://doi.org/10.15690/vramn.v67i3.186.
2. Zoeller R.T., Brown T.R., Doan L.L., Gore A.C., Skakkebaek N.E., Soto A.M., Woodruff T.J., Vom Saal F.S. Endocrine-disrupting chemicals and public health protection: a statement of principles from the Endocrine Society. Endocrinology 2012; 153(9): 4097–4110, https://doi.org/10.1210/en.2012-1422.
3. Bachman M.J., Keller J.M., West K.L., Jensen B.A. Persistent organic pollutant concentrations in blubber of 16 species of cetaceans stranded in the Pacific Islands from 1997 through 2011. Sci Total Environ 2014; 488–489: 115–123, https://doi.org/10.1016/j.scitotenv.2014.04.073.
4. World Health Organization. Pesticide residues in food — 2016 evaluations. Part II — toxicological. Geneva: 2017.
5. Zala S.M., Penn D.J. Abnormal behaviours induced by chemical pollution: a review of the evidence and new challenges. Anim Behav 2004; 68(4): 649–664, https://doi.org/10.1016/j.anbehav.2004.01.005.
6. Hatcher J.M., Delea K.C., Richardson J.R., Pennell K.D., Miller G.W. Disruption of dopamine transport by DDT and its metabolites. Neurotoxicology 2008; 29(4): 682–690, https://doi.org/10.1016/j.neuro.2008.04.010.
7. Yaglova N.V., Tsomartova D.A., Yaglov V.V. Effect of prenatal and postnatal exposure to low doses of DDT on catecholamine secretion in rats in different period of ontogeny. Bull Exp Biol Med 2017; 163: 422–424. https://doi.org/10.1007/s10517-017-3819-6.
8. Yaglova N.V., Tsomartova D.A., Yaglov V.V., Obernikhin S.S., Nazimova S.V. Altered secretion of adrenomedullary a-cells in rats after developmental exposure to low doses of dichlorodiphenyltrichloroethane. Klinicheskaya i eksperimental’naya morfologiya 2018; 3(27): 30–34, https://doi.org/10.31088/2226-5988-2018-27-3-30-34.
9. Tekhnicheskiy reglament Tamozhennogo soyuza TR TS 021/2011 “O bezopasnosti pishchevoy produktsii” [Technical regulations of the Customs Union TR CU 021/2011 “On the safety of food products”]. Saint Petersburg: GIORD; 2015. 176 p.
10. Pignatelli D., Xiao F., Gouveia A.M., Ferreira J.G., Vinson G.P. Adrenarche in the rat. J Endocrinol 2006; 191(1): 301–308, https://doi.org/10.1677/joe.1.06972.
11. Chumasov E.I., Atagimov M.Z., Sokolov V.I., Seliverstova V.G. The development of chromaffin adrenal gland tissue. Morfologiya 2003; 123(3): 68–73.
12. Grigoriev I.P., Vasilenko M.S., Sukhorukova E.G., Korzhevskii D.E. Use of different antibodies to tyrosine hydroxylase to study catecholaminergic systems in the mammalian brain. Neurosci Behav Physi 2012; 42(2): 210–213, https://doi.org/10.1007/s11055-011-9555-x.
13. Chumasov E., Alekseenko A., Petrova E., Korzhevsky D. Study of the nervous apparatus of the heart of rats of different age by immunohistochemical markers. Mezhdunarodnyy vestnik veterinarii 2017; 1: 41–46.
14. Yaglova N.V., Yaglov V.V. Cytophysiological changes in the follicular epithelium of the thyroid gland after long-term exposure to low doses of dichlorodiphenyltrichloroethane (DDT). Bull Exp Biol Med 2017; 162: 699–702, https://doi.org/10.1007/s10517-017-3691-4.
15. Ruuskanen S., Espín S., Sánchez-Virosta P., Sarraude T., Hsu B.Y., Pajunen P., Costa R.A., Eens M., Hargitai R., Török J., Eeva T. Transgenerational endocrine disruption: does elemental pollution affect egg or nestling thyroid hormone levels in a wild songbird? Environ Pollut 2019; 247: 725–735, https://doi.org/10.1016/j.envpol.2019.01.088.
16. Bornman M., Delport R., Farías P., Aneck-Hahn N., Patrick S., Millar R.P., de Jager C. Alterations in male reproductive hormones in relation to environmental DDT exposure. Environ Int 2018; 113: 281–289, https://doi.org/10.1016/j.envint.2017.12.039.
17. Mhaouty-Kodja S., Naulé L., Capela D. Sexual behavior: from hormonal regulation to endocrine disruption. Neuroendocrinology 2019; 107(4): 400–416, https://doi.org/10.1159/000494558.

Timokhina E.P., Nazimova S.V., Tsomartova D.A., Yaglova N.V., Obernikhin S.S., Yaglov V.V. Morphological and Cytophysiological Changes in the Adult Rat Adrenal Medulla after Prenatal and Postnatal Exposure to Endocrine-Disrupting DDT. Sovremennye tehnologii v medicine 2020; 12(2): 50, https://doi.org/10.17691/stm2020.12.2.06