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Effect of Disulfiram on the Reproductive Capacity of Female Mice
Mingming Teng1, Yuan Luo1, Chan Wang1
1Shaanxi Stem Cell Engineering and Technology Research Center, College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China.
Abstract:
In the process of assisted reproduction, the high-oxygen in vitro environment can easily cause oxidative damage to oocytes. Disulfiram (DSF) can play an anti-oxidant or pro-oxidant role in different cells, and the effect of DSF on oocytes remains unclear. Moreover, it remains unclear whether the use of DSF in the early stages of pregnancy has a negative impact on the fetus. In this study, we found that DSF increased serum FSH levels and increased the ovulation rate in mice. Moreover, DSF enhanced the antioxidant capacity of oocytes and contributed to the success rate of in vitro fertilization. Moreover, the use of DSF in early pregnancy in mice increased the uterine horn volume and the degree of vascularization, which contributed to a successful pregnancy. In addition, it was found that DSF regulated the mRNA expression of angiogenesis-related genes (VEGF), follicular development-related genes (C1QTNF3, mTOR and PI3K), ovulation-related genes (MAPK1, MAPK3 and p38 MAPK) and antioxidant-related genes (GPX4 and CAT). These results indicate that DSF is helpful for increasing the antioxidant capacity of oocytes and the ovulation rate. In early pregnancy in mice, DSF promotes pregnancy by increasing the degree and volume of uterine vascularization.
Insights
Disulfiram (DSF) boosts ovulation rates and oocyte antioxidant capacity, improving in vitro fertilization success. In early pregnancy, DSF enhances uterine vascularization, promoting successful gestation in mice.
Area of Science:
- Reproductive Biology
- Pharmacology
- Oxidative Stress Research
Background:
- Assisted reproduction faces challenges from high-oxygen environments causing oocyte oxidative damage.
- Disulfiram's (DSF) dual antioxidant/pro-oxidant role is cell-dependent, with its effect on oocytes and early pregnancy impact being previously unclear.
Purpose of the Study:
- To investigate the effect of Disulfiram (DSF) on oocyte quality, ovulation rates, and pregnancy outcomes in a mouse model.
- To determine if DSF influences key genes related to angiogenesis, follicular development, ovulation, and antioxidant defense.
Main Methods:
- Administration of DSF to mice to assess effects on serum FSH, ovulation rates, and oocyte antioxidant capacity.
- Evaluation of in vitro fertilization success rates and pregnancy outcomes, including uterine vascularization.
- Analysis of mRNA expression for genes involved in angiogenesis (VEGF), follicular development (C1QTNF3, mTOR, PI3K), ovulation (MAPK1, MAPK3, p38 MAPK), and antioxidant defense (GPX4, CAT).
Main Results:
- DSF significantly increased serum FSH levels and ovulation rates in mice.
- DSF enhanced oocyte antioxidant capacity and improved in vitro fertilization success rates.
- DSF administration during early pregnancy increased uterine horn volume and vascularization, correlating with successful pregnancies.
- DSF modulated the expression of key genes involved in angiogenesis, follicular development, ovulation, and antioxidant pathways.
Conclusions:
- Disulfiram (DSF) demonstrates a beneficial role in improving oocyte quality and ovulation rates, potentially aiding assisted reproduction.
- DSF promotes successful pregnancy in mice by enhancing uterine vascularization during early gestation.
- DSF's regulation of specific gene pathways highlights its potential as a therapeutic agent in reproductive contexts.
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