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 language | English (US) |
|---|---|
| Article number | e12577 |
| Journal | Journal of pineal research |
| DOIs | |
| State | Published - Jan 1 2019 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - 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
AU - Liu, Jing Cai
AU - Li, Lan
AU - Yan, Hong Chen
AU - Zhang, Teng
AU - Zhang, Pan
AU - Sun, Zhong Yi
AU - De Felici, Massimo
AU - Reiter, Russel J
AU - Shen, Wei
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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.
AB - 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.
KW - apoptosis
KW - DEHP
KW - melatonin
KW - primordial follicle assembly
KW - Xdh
UR - http://www.scopus.com/inward/record.url?scp=85064680302&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85064680302&partnerID=8YFLogxK
U2 - 10.1111/jpi.12577
DO - 10.1111/jpi.12577
M3 - Article
C2 - 30938853
AN - SCOPUS:85064680302
JO - Journal of Pineal Research
JF - Journal of Pineal Research
SN - 0742-3098
M1 - e12577
ER -