Prenatal to peripubertal exposure to Di(2-ethylhexyl) phthalate induced endometrial atrophy and fibrosis in female mice

Jisun Lee, Sun Hee Chang, Yoon Hee Cho, Jin Su Kim, Hyeongi Kim, Javeria Zaheer, Gowoon Lee, Kyungho Choi, Yeong Sook Yoon, Young Ah Kim

Research output: Contribution to journalArticlepeer-review

Abstract

Di(2-ethylhexy) phthalate (DEHP) is a widely used plasticizer that is ubiquitously found in the environment. Using a mouse model, we investigated the impact of early life DEHP exposure ranging from the prenatal to peripubertal developmental period of the female reproductive system. Pregnant female mice were allocated to three groups as follows: control, 100 mg/kg/day, and 500 mg/kg/day DEHP treatment. DEHP exposure was introduced through feeding during pregnancy (3 weeks) and lactation (3 weeks). After weaning, the offspring were also exposed to DEHP through feeding for another 2 weeks. Observations were conducted on female offspring at 10 and 24 weeks. The number of live offspring per dam was significantly lower in the high-DEHP-exposed group (500 mg/kg/day) compared to the control group (7.67 ± 1.24 vs. 14.17 ± 0.31; p < 0.05) despite no difference in pregnancy rates across the groups. Low-DEHP exposure (100 mg/kg/day) resulted to a decreased body weight (36.07 ± 3.78 vs. 50.11 ± 2.11 g; p < 0.05) and decreased left uterine length (10.60 ± 1.34 vs. 14.77 ± 0.82 mm; p < 0.05) in 24-week- old female mice. As early as 10 weeks, endometrial atrophy and fibrosis were observed, and endometrial cystic hyperplasia was noted in female mice at 24 weeks. Our study is the first to demonstrate that female mice exposed to DEHP in the early life developed endometrial fibrosis in the female offspring. Further studies on the consequences of these observations in fecundity and other reproductive functions are warranted.

Original languageEnglish
Article number115798
Pages (from-to)115798
JournalEcotoxicology and Environmental Safety
Volume269
DOIs
StatePublished - Jan 1 2024

Keywords

  • Body weight
  • Di(2-ethiylhexy) phthalate
  • Endometrial atrophy
  • Endometrial cystic hyperplasia
  • Fibrosis
  • Prenatal to peripubertal exposure
  • Pregnancy
  • Diethylhexyl Phthalate/toxicity
  • Prenatal Exposure Delayed Effects
  • Phthalic Acids
  • Humans
  • Female

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