Browse > Article
http://dx.doi.org/10.12717/DR.2021.25.4.257

A Chronic-Low-Dose Exposing of DEHP with OECD TG 443 Altered the Histological Characteristics and Steroidogeic Gene Expression of Adrenal Gland in Female Mice  

Lee, Bo Young (Division of Developmental Biology and Physiology, Center for Development and Program Research, Department of Biotechnology, Institute of Basic Sciences, Sungshin University)
Jo, Jeong Bin (Division of Developmental Biology and Physiology, Center for Development and Program Research, Department of Biotechnology, Institute of Basic Sciences, Sungshin University)
Choi, Donchan (Dept. of Life Science, College of Environmental Sciences, Yong-In University)
Lee, Sung-Ho (Dept. of Biotechnology, Sangmyung University)
Cheon, Yong-Pil (Division of Developmental Biology and Physiology, Center for Development and Program Research, Department of Biotechnology, Institute of Basic Sciences, Sungshin University)
Publication Information
Development and Reproduction / v.25, no.4, 2021 , pp. 257-268 More about this Journal
Abstract
Phthalates and their metabolites are well-known endocrine disrupting chemicals. Di-(2-ethylhexyl) phthalate (DEHP) has been widely used in industry and the exposing possibility to adult is high. In this study, DEHP was treated (133 ㎍/L and 1,330 ㎍/L in drinking water) according to the OECD test guideline 443 to mature female mice and their adrenal gland were examined for histological characteristics and steroidogenic gene expression. The wet weight of the adrenal gland was increased in all administrated groups compared to control. The diameter of zona fasciculata (ZF) was increased by DEHP in both outer ZF and inner ZF but there was no difference in morphology of the cells and arrangements into zona between groups. In addition, the arrangement of extracellular matrix was not different between control and DEHP groups. CYP11B1 was mainly localized at ZF and the intensity was not different between groups. DAX1 was localized in zona glomerulosa (ZG) and ZF, and its expression levels were decreased by DEHP administration. Its level was lower in DEHP133 group than DEHP1330 group. On the other hand, CYP17A1 was localized in ZG of DEHP1330 group. These results suggest that chronic low-dose DEHP exposing may modify the microstructure and function of the adrenal cortical cortex.
Keywords
Di-(2-ethylhexyl) phthalate; Adrenal gland; CYP11B1; CYP17A1; DAX1; Endocrine disrupting chemical;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Kariyazono Y, Taura J, Hattori Y, Ishii Y, Narimatsu S, Fujimura M, Takeda T, Yamada H (2015) Effect of in utero exposure to endocrine disruptors on fetal steroidogenesis governed by the pituitary-gonad axis: A study in rats using different ways of administration. J Toxicol Sci 40:909-916.   DOI
2 Crobeddu B, Ferraris E, Kolasa E, Plante I (2019) Di(2-ethylhexyl) phthalate (DEHP) increases proliferation of epithelial breast cancer cells through progesterone receptor dysregulation. Environ Res 173:165-173.   DOI
3 Ito Y, Kamijima M, Nakajima T (2019) Di(2-ethylhexyl) phthalate-induced toxicity and peroxisome proliferator-activated receptor alpha: A review. Environ Health Prev Med 24:47.   DOI
4 Komar CM, Braissant O, Wahli W, Curry TE Jr (2001) Expression and localization of PPARs in the rat ovary during follicular development and the periovulatory period. Endocrinology 142:4831-4838.   DOI
5 Maloney EK, Waxman DJ (1999) trans-Activation of PPARα and PPARγ by structurally diverse environmental chemicals. Toxicol Appl Pharmacol 161:209-218.   DOI
6 Martinez-Arguelles DB, Papadopoulos V (2015) Mechanisms mediating environmental chemical-induced endocrine disruption in the adrenal gland. Front Endocrinol 6:29.   DOI
7 Niakan KK, McCabe ERB (2005) DAX1 origin, function, and novel role. Mol Genet Metab 86:70-83.   DOI
8 Tyl RW, Price CJ, Marr MC, Kimmel CA (1988) Developmental toxicity evaluation of dietary di(2-ethylhexyl)phthalate in Fischer 344 rats and CD-1 mice. Fundam Appl Toxicol 10:395-412.   DOI
9 Zeiger E, Haworth S, Mortelmans K, Speck W (1985) Mutagenicity testing of di(2-ethylhexyl) phthalate and related chemicals in Salmonella. Environ Mutagen 7:213-232.   DOI
10 Zhang NN, Wang CN, Ni X (2020) Construction of transgenic mice with specific Cre recombinase expression in the zona fasciculata in adrenal cortex. Sheng Li Xue Bao 72:148-156.
11 Martinez-Arguelles DB, Culty M, Zirkin BR, Papadopoulos V (2009) In utero exposure to di-(2-ethylhexyl) phthalate decreases mineralocorticoid receptor expression in the adult testis. Endocrinology 150:5575-5585.   DOI
12 Martinez-Arguelles DB, Guichard T, Culty M, Zirkin BR, Papadopoulos V (2011) In utero exposure to the antiandrogen di-(2-ethylhexyl) phthalate decreases adrenal aldosterone production in the adult rat. Biol Reprod 85:51-61.   DOI
13 Kim CL, Cha SY, Chun MY, Kim B, Choi MY, Cheon YP (2015) Positive effects of diphlorethohydroxycarmalol (DPHC) on the stability of the integument structure in diet-induced obese female mice. Dev Reprod 19:145-152.   DOI
14 Lorz PM, Towae FK, Enke W, Jackh R, Bhargava N, Hillesheim W (2012) Ullmann's Encyclopedia of Industrial Chemistry. John Wiley & Sons, New York, NY.
15 Simon C, Onghena M, Covaci A, Van Hoeck E, Van Loco J, Vandermarken T, Van Langenhove K, Demaegdt H, Mertens B, Vandermeiren K, Scippo ML, Elskens M (2016) Screening of endocrine activity of compounds migrating from plastic baby bottles using a multi-receptor panel of in vitro bioassays. Toxicol In Vitro 37:121-133.   DOI
16 Ragazzon B, Lefrancois-Martinez AM, Val P, Sahut-Barnola I, Tournaire C, Chambon C, Gachancard-Bouya JL, Begue RJ, Veyssiere G, Martinez A (2006) Adrenocorticotropin-dependent changes in SF-1/DAX-1 ratio influence steroidogenic genes expression in a novel model of glucocorticoid-producing adrenocortical cell lines derived from targeted tumorigenesis. Endocrinology 147:1805-1818.   DOI
17 Richardson KA, Hannon PR, Johnson-Walker YJ, Myint MS, Flaws JA, Nowak RA (2018) Di (2-ethylhexyl) phthalate (DEHP) alters proliferation and uterine gland numbers in the uteri of adult exposed mice. Reprod Toxicol 77:70-79.   DOI
18 Lyraki R, Schedl A (2021) Adrenal cortex renewal in health and disease. Nat Rev Endocrinol 17:421-434.   DOI
19 Scheys JO, Heaton JH, Hammer GD (2011) Evidence of adrenal failure in aging Dax1-deficient mice. Endocrinology 152:3430-3439.   DOI
20 McCabe ERB (2001) Adrenal hypoplasias and aplaisas. In: Scriver CR, Beaudet AL, Sly WS, Valle D, Childs B, Kinzler KW, Vogelstein B (eds), The Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill, New York, NY, pp 4263-4274.
21 Turcu AF, Nanba AT, Auchus RJ (2018) The rise, fall, and resurrection of 11-oxygenated androgens in human physiology and disease. Horm Res Paediatr 89:284-291.   DOI
22 United States Environmental Protection Agency (2013) America's Children and the Environment. 3rd ed. United States Environmental Protection Agency, Washington, DC, p 304.
23 Vandenberg LN, Hunt PA, Gore AC (2019) Endocrine disruptors and the future of toxicology testing - lessons from CLARITY - BPA. Nat Rev Endocrinol 15:366-374.   DOI
24 Chen X, Xu S, Tan T, Lee ST, Cheng SH, Lee FW, Xu SJL, Ho KC (2014) Toxicity and estrogenic endocrine disrupting activity of phthalates and their mixtures. Int J Environ Res Public Health 11:3156-3168.   DOI
25 Ahmad S, Sharma S, Afjal MA, Habib H, Akhter J, Goswami P, Parvez S, Akhtar M, Raisuddin S (2022) mRNA expression and protein-protein interaction (PPI) network analysis of adrenal steroidogenesis in response to exposure to phthalates in rats. Environ Toxicol Pharmacol 89:103780.   DOI
26 Bloom MS, Whitcomb BW, Chen Z, Ye A, Kannan K, Louis GMB (2015) Associations between urinary phthalate concentrations and semen quality parameters in a general population. Hum Reprod 30:2645-2657.   DOI
27 Cha S, Baek JW, Ji HJ, Choi JH, Kim C, Lee MY, Hwang YJ, Yang E, Lee SH, Jung HI, Cheon YP (2017) Disturbing effects of chronic low-dose 4-nonylphenol exposing on gonadal weight and reproductive outcome over one-generation. Dev Reprod 21:121-130.   DOI
28 Cheon YP (2020) Di-(2-ethylhexyl) phthalate (DEHP) and uterine histological characteristics. Dev Reprod 24:1-17.   DOI
29 Dumontet T, Martinez A (2021) Adrenal androgens, adrenarche, and zona reticularis: A human affair? Mol Cell Endocrinol 528:111239.   DOI
30 Gummow BM, Scheys JO, Cancelli VR, Hammer GD (2006) Reciprocal regulation of a glucocorticoid receptor-steroidogenic factor-1 transcription complex on the Dax-1 promoter by glucocorticoids and adrenocorticotropic hormone in the adrenal cortex. Mol Endocrinol 20:2711-2723.   DOI
31 Lovekamp-Swan T, Davis BJ (2003) Mechanisms of phthalate ester toxicity in the female reproductive system. Environ Health Perspect 111:139-145.   DOI
32 Kim AC, Reuter AL, Zubair M, Else T, Serecky K, Bingham NC, Lavery GG, Parker KL, Hammer GD (2008) Targeted disruption of β-catenin in Sf1-expressing cells impairs development and maintenance of the adrenal cortex. Development 135:2593-2602.   DOI
33 Koch HM, Bolt HM, Angerer J (2004) Di(2-ethylhexyl)phthalate (DEHP) metabolites in human urine and serum after a single oral dose of deuterium-labelled DEHP. Arch Toxicol 78:123-130.   DOI
34 Martinez-Razo LD, Martinez-Ibarra A, Vazquez-Martinez ER, Cerbon M (2021) The impact of di-(2-ethylhexyl) phthalate and mono(2-ethylhexyl) phthalate in placental development, function, and pathophysiology. Environ Int 146:106228.   DOI
35 Kosir R, Zmrzljak UP, Bele T, Acimovic J, Perse M, Majdic G, Prehn C, Adamski J, Rozman D (2012) Circadian expression of steroidogenic cytochromes P450 in the mouse adrenal gland - involvement of cAMP-responsive element modulator in epigenetic regulation of Cyp17a1. FEBS J 279:1584-1593.   DOI
36 Li X, Fang EF, Scheibye-Knudsen M, Cui H, Qiu L, Li J, He Y, Huang J, Bohr VA, Ng TB, Guo H (2014) Di-(2-ethylhexyl) phthalate inhibits DNA replication leading to hyperPARylation, SIRT1 attenuation and mitochondrial dysfunction in the testis. Sci Rep 4:6434.   DOI