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

Am J Perinatol. 2018 Nov;35(13):1251-1259. doi: 10.1055/s-0038-1642027. Epub 2018 May 1.


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 Ki-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 Ki-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 Ki-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.

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Animals
  • Animals, Newborn
  • Diethylhexyl Phthalate / pharmacology*
  • Disaccharidases / metabolism
  • Female
  • Fetal Organ Maturity / drug effects
  • Gestational Age
  • Intestine, Small* / growth & development
  • Intestine, Small* / pathology
  • Lactation
  • Phthalic Acids / pharmacology*
  • Pregnancy
  • Prenatal Exposure Delayed Effects* / chemically induced
  • Prenatal Exposure Delayed Effects* / metabolism
  • Prenatal Exposure Delayed Effects* / pathology
  • Rats
  • Rats, Wistar


  • Phthalic Acids
  • diisononyl phthalate
  • Diethylhexyl Phthalate
  • Alkaline Phosphatase
  • Disaccharidases
  • diethyl phthalate