Effect of Gestational and Lactational Exposure to DEHP, DINP, and DEP on Intestinal Morphology, Disaccharidases, and Alkaline Phosphatase in Rats during Postnatal Development

K. Setti Ahmed; O. Kharoubi; A. E. K. Aoues; M. Bouchekara; B. Khaladi; M. Taleb

doi:10.1055/s-0038-1642027

American Journal of Perinatology, Inhaltsverzeichnis

Am J Perinatol 2018; 35(13): 1251-1259
DOI: 10.1055/s-0038-1642027

Original Article

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Effect of Gestational and Lactational Exposure to DEHP, DINP, and DEP on Intestinal Morphology, Disaccharidases, and Alkaline Phosphatase in Rats during Postnatal Development

K. Setti Ahmed

¹Department of Biology, Faculty of NLS, University of Mascara, Mascara, Algeria

²Department of Biology, Laboratory of BTE-BD-PR Oran, Faculty of LNS, University of Oran 1 Ahmed Ben Bella, Oran, Algeria

,

O. Kharoubi

²Department of Biology, Laboratory of BTE-BD-PR Oran, Faculty of LNS, University of Oran 1 Ahmed Ben Bella, Oran, Algeria

,

A. E. K. Aoues

²Department of Biology, Laboratory of BTE-BD-PR Oran, Faculty of LNS, University of Oran 1 Ahmed Ben Bella, Oran, Algeria

,

M. Bouchekara

¹Department of Biology, Faculty of NLS, University of Mascara, Mascara, Algeria

,

B. Khaladi

³Department of Anathomopatology, MeslemTayeb Hospital, Mascara, Algeria

,

M. Taleb

¹Department of Biology, Faculty of NLS, University of Mascara, Mascara, Algeria

› Institutsangaben

Abstract

Introduction The diesters of 1,2-benzenedicarboxylic acid (phthalic acid), commonly known as phthalates, are used primarily as plasticizers of polyvinyl chloride and as additives in consumer and personal care products.

Objective This study was designed to evaluate the impact of in utero and postnatal exposure to diisononyl phthalate (DINP), diethylhexyl phthalate (DEHP), and diethyl phthalate (DEP) on gut maturation in a Wistar rat model.

Materials and Methods Pregnant females were gavaged from day 8 of gestation through postnatal day (pd) 30 with 0 (vehicle control), DEHP (380 mg/kg/d), DINP (380 mg/kg/d), or DEP (800 mg/kg/d) dissolved in corn oil. Intestinal samples have been collected at 0, 7, 14, 21, and 30 pd for histological and biochemical analysis. The mitotic index has been evaluated based on the expression of K_i-67 antigen.

Results All tested phthalate treatments have significantly decreased the body as well as the organ's weight (p < 0.001). DINP exposure resulted in severe villous atrophy, while DEHP treated group was characterized by lymphoepithelial lesions. In addition, a significant decrease of the K_i-67 proliferation index was observed in the youngest rats (0 and 7 days) upon the various treatments (p < 0.0001), whereas at day 30, an increased numbers of K_i-67 positive cells were observed in DEHP and DEP but bot DINP group. Lactase and sucrase activities were inhibited by DEP in contrast to DINP and DEHP which increased enzymes activity (p < 0.05).

Conclusion Our results suggest that exposure to phthalates during gestational and lactational phases negatively impacts the development of the small intestine.

Keywords

gut maturation - phthalates - in utero - postnatal - disaccharidases - K_i-67 - ALK

Volltext

Referenzen

References
1 Xu H, Ghishan FK. Molecular Physiology of Gastrointestinal Function During Development. In: Physiology of the Gastrointestinal Tract. 6th ed. Elsevier Inc.; 2018: 235-269
2 Wild GE, Searles LE, Koski KG, Drozdowski LA, Begum-Hasan J, Thomson ABR. Oral polyamine administration modifies the ontogeny of hexose transporter gene expression in the postnatal rat intestine. Am J Physiol Gastrointest Liver Physiol 2007; 293 (02) G453-G460
3 Hauser R, Calafat AM. Phthalates and human health. Occup Environ Med 2005; 62 (11) 806-818
4 Becker K, Seiwert M, Angerer J. , et al. DEHP metabolites in urine of children and DEHP in house dust. Int J Hyg Environ Health 2004; 207 (05) 409-417
5 Chou YY, Huang PC, Lee CC, Wu MH, Lin SJ. Phthalate exposure in girls during early puberty. J Pediatr Endocrinol Metab 2009; 22 (01) 69-77
6 Huang PC, Tien CJ, Sun YM, Hsieh CY, Lee CC. Occurrence of phthalates in sediment and biota: relationship to aquatic factors and the biota-sediment accumulation factor. Chemosphere 2008; 73 (04) 539-544
7 Adibi JJ, Perera FP, Jedrychowski W. , et al. Prenatal exposures to phthalates among women in New York City and Krakow, Poland. Environ Health Perspect 2003; 111 (14) 1719-1722
8 Rudel RA, Camann DE, Spengler JD, Korn LR, Brody JG. Phthalates, alkylphenols, pesticides, polybrominated diphenyl ethers, and other endocrine-disrupting compounds in indoor air and dust. Environ Sci Technol 2003; 37 (20) 4543-4553
9 Li X, Fang EF, Scheibye-Knudsen M. , et al. Di-(2-ethylhexyl) phthalate inhibits DNA replication leading to hyperPARylation, SIRT1 attenuation, and mitochondrial dysfunction in the testis. Sci Rep 2014; 4: 6434
10 Mahood IK, Hallmark N, McKinnell C, Walker M, Fisher JS, Sharpe RM. Abnormal Leydig cell aggregation in the fetal testis of rats exposed to di (n-butyl) phthalate and its possible role in testicular dysgenesis. Endocrinology 2005; 146 (02) 613-623
11 Hu X, Shi W, Zhang F. , et al. In vitro assessment of thyroid hormone disrupting activities in drinking water sources along the Yangtze River. Environ Pollut 2013; 173: 210-215
12 Upson K, Sathyanarayana S, De Roos AJ. , et al. Phthalates and risk of endometriosis. Environ Res 2013; 126: 91-97
13 Swan SH. Environmental phthalate exposure in relation to reproductive outcomes and other health endpoints in humans. Environ Res 2008; 108 (02) 177-184
14 Main KM, Mortensen GK, Kaleva MM. , et al. Human breast milk contamination with phthalates and alterations of endogenous reproductive hormones in infants three months of age. Environ Health Perspect 2006; 114 (02) 270-276
15 Bornehag CG, Sundell J, Weschler CJ. , et al. The association between asthma and allergic symptoms in children and phthalates in house dust: a nested case-control study. Environ Health Perspect 2004; 112 (14) 1393-1397
16 Dahlqvist A. Method for assay of intestinal disaccharidase. Anal Biochem 1964; 7: 18-25
17 Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193 (01) 265-275
18 Bessy OA, Lowry OH, Brock MJ. A method of rapid determination of alkaline phosphatase with five cubic millimeters of serum. J Biol Chem 1946; 146: 321-329
19 Borch J, Metzdorff SB, Vinggaard AM, Brokken L, Dalgaard M. Mechanisms underlying the anti-androgenic effects of diethylhexyl phthalate in fetal rat testis. Toxicology 2006; 223 (1-2): 144-155
20 Kim HS, Kim TS, Shin JH. , et al. Neonatal exposure to di(n-butyl) phthalate (DBP) alters male reproductive-tract development. J Toxicol Environ Health A 2004; 67 (23-24): 2045-2060
21 Marsee K, Woodruff TJ, Axelrad DA, Calafat AM, Swan SH. Estimated daily phthalate exposures in a population of mothers of male infants exhibiting reduced anogenital distance. Environ Health Perspect 2006; 114 (06) 805-809
22 Sharpe RM, Fisher JS, Millar MM, Jobling S, Sumpter JP. Gestational and lactational exposure of rats to xenoestrogens results in reduced testicular size and sperm production. Environ Health Perspect 1995; 103 (12) 1136-1143
23 Tanaka T. Reproductive and neurobehavioural toxicity study of bis(2-ethylhexyl) phthalate (DEHP) administered to mice in the diet. Food Chem Toxicol 2002; 40 (10) 1499-1506
24 Tanaka T. Effects of bis(2-ethylhexyl) phthalate (DEHP) on secondary sex ratio of mice in a cross-mating study. Food Chem Toxicol 2003; 41 (10) 1429-1432
25 Tanaka T. Reproductive and neurobehavioural effects of bis(2-ethylhexyl) phthalate (DEHP) in a cross-mating toxicity study of mice. Food Chem Toxicol 2005; 43 (04) 581-589
26 National Toxicology Program. Di(2-ethylhexyl)phthalate: reproduction and fertility assessment inCD-1micewhenadministered by gavage. Final Report NTP-84–079. Research Triangle Park, NC: National Toxicology Program; 1984
27 Marsman D. NTP technical report on the toxicity studies of dibutyl phthalate (CAS No. 84–74–2) administered in feed to F344/N Rats and B6C3F1 Mice. Toxic Rep Ser 1995; 30: 1-G5
28 Zhang Y, Lin L, Cao Y, Chen B, Zheng L, Ge RS. Phthalate levels and low birth weight: a nested case-control study of Chinese newborns. J Pediatr 2009; 155 (04) 500-504
29 Desvergne B, Feige JN, Casals-Casas C. PPAR-mediated activity of phthalates: a link to the obesity epidemic?. Mol Cell Endocrinol 2009; 304 (1-2): 43-48
30 Grün F, Blumberg B. Environmental obesogens: organotins and endocrine disruption via nuclear receptor signaling. Endocrinology 2006; 147 (6, Suppl): S50-S55
31 Dostal LA, Weaver RP, Schwetz BA. Transfer of di(2-ethylhexyl) phthalate through rat milk and effects on milk composition and the mammary gland. Toxicol Appl Pharmacol 1987; 91 (03) 315-325
32 Latini G, De Felice C, Presta G. , et al. Exposure to di(2-ethylhexyl)phthalate in humans during pregnancy. A preliminary report. Biol Neonate 2003; 83 (01) 22-24
33 McKee RH, Butala JH, David RM, Gans G. NTP center for the evaluation of risks to human reproduction reports on phthalates: addressing the data gaps. Reprod Toxicol 2004; 18 (01) 1-22
34 Loff S, Kabs F, Witt K. , et al. Polyvinylchloride infusion lines expose infants to large amounts of toxic plasticizers. J Pediatr Surg 2000; 35 (12) 1775-1781
35 Xu Y, Cook TJ, Knipp GT. Effects of di-(2-ethylhexyl)-phthalate (DEHP) and its metabolites on fatty acid homeostasis regulating proteins in rat placental HRP-1 trophoblast cells. Toxicol Sci 2005; 84 (02) 287-300
36 Rusyn I, Peters JM, Cunningham ML. Modes of action and species-specific effects of di-(2-ethylhexyl)phthalate in the liver. Crit Rev Toxicol 2006; 36 (05) 459-479
37 Wang L, Li J, Li Q, Zhang J, Duan X-L. Morphological changes of cell proliferation and apoptosis in rat jejunal mucosa at different ages. World J Gastroenterol 2003; 9 (09) 2060-2064
38 Baintner K. Transmission of antibodies from mother to young: evolutionary strategies in a proteolytic environment. Vet Immunol Immunopathol 2007; 117 (3-4): 153-161
39 Walthall K, Cappon GD, Hurtt ME, Zoetis T. Postnatal development of the gastrointestinal system: a species comparison. Birth Defects Res B Dev Reprod Toxicol 2005; 74 (02) 132-156
40 Thompson CM, Proctor DM, Suh M, Haws LC, Kirman CR, Harris MA. Assessment of the mode of action underlying development of rodent small intestinal tumors following oral exposure to hexavalent chromium and relevance to humans. Crit Rev Toxicol 2013; 43 (03) 244-274
41 Murphy CJ, Stermer AR, Richburg JH. Age- and species-dependent infiltration of macrophages into the testis of rats and mice exposed to mono-(2-Ethylhexyl) phthalate (MEHP). Biol Reprod 2014; 91 (01) 18
42 Campioli E, Martinez-Arguelles DB, Papadopoulos V. In utero exposure to the endocrine disruptor di-(2-ethylhexyl) phthalate promotes local adipose and systemic inflammation in adult male offspring. Nutr Diabetes 2014; 4: e115
43 Ferguson KK, Cantonwine DE, Rivera-González LO. , et al. Urinary phthalate metabolite associations with biomarkers of inflammation and oxidative stress across pregnancy in Puerto Rico. Environ Sci Technol 2014; 48 (12) 7018-7025
44 Proulx P. Biochim Biophys Acta 1991; 1071: 255-271
45 Lebenthal E, Sunshine P, Kretchmer N. Effect of prolonged nursing on the activity of intestinal lactase in rats. Gastroenterology 1973; 64 (06) 1136-1141
46 Hu J, Raikhel V, Gopalakrishnan K. , et al. Effect of postnatal low-dose exposure to environmental chemicals on the gut microbiome in a rodent model. Microbiome 2016; 4 (01) 26