Identification of oxidative stress–related Xdh gene as a di(2-ethylhexyl)phthalate (DEHP) target and the use of melatonin to alleviate the DEHP-induced impairments in newborn mouse ovaries

Jing Cai Liu, Lan Li, Hong Chen Yan, Teng Zhang, Pan Zhang, Zhong Yi Sun, Massimo De Felici, Russel J Reiter, Wei Shen

Research output: Contribution to journalArticle

Abstract

This study, using an in vitro ovary culture model, investigates the mechanisms through which di(2-ethylhexyl)phthalate (DEHP) impairs germ cell cyst breakdown and primordial follicle assembly. The results indicate the latter effects exerted by 10 or 100 µmol/L DEHP in cultured newborn ovaries were associated with increased levels of reactive oxygen species (ROS) and apoptosis. Based on a transcriptome analysis, we found the expression of the oxidative stress–related gene Xdh (xanthine dehydrogenase) was significantly upregulated in DEHP-cultured ovaries. Two treatments, namely Xdh RNAi or the addition of melatonin to the ovary culture, inhibited the increase in Xdh expression and ROS levels caused by DEHP and, at the same time, reduced apoptosis and the impairment of primordial follicle assembly in the treated ovaries. Together, the results identify Xdh gene as one of the major targets of DEHP in newborn ovaries and that the consequent increased level of ROS is possibly responsible for the increment of apoptosis and primordial follicle assembly impairment. At the same time, they highlight that melatonin alleviates the effects of DEHP as with other endocrine-disrupting compounds on the ovary.

Original languageEnglish (US)
Article numbere12577
JournalJournal of pineal research
DOIs
StatePublished - Jan 1 2019
Externally publishedYes

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Xanthine Dehydrogenase
Melatonin
Ovary
Genes
Reactive Oxygen Species
Apoptosis
Gene Expression Profiling
RNA Interference
phthalic acid
Germ Cells
Cysts

Keywords

  • apoptosis
  • DEHP
  • melatonin
  • primordial follicle assembly
  • Xdh

ASJC Scopus subject areas

  • Endocrinology

Cite this

Identification of oxidative stress–related Xdh gene as a di(2-ethylhexyl)phthalate (DEHP) target and the use of melatonin to alleviate the DEHP-induced impairments in newborn mouse ovaries. / Liu, Jing Cai; Li, Lan; Yan, Hong Chen; Zhang, Teng; Zhang, Pan; Sun, Zhong Yi; De Felici, Massimo; Reiter, Russel J; Shen, Wei.

In: Journal of pineal research, 01.01.2019.

Research output: Contribution to journalArticle

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