Repeated Superovulation via PMSG/hCG Administration Induces 2-Cys Peroxiredoxins Expression and Overoxidation in the Reproductive Tracts of Female Mice원문보기
Superovulation induced by exogenous gonadotropin treatment (PMSG/hCG) increases the number of available oocytes in humans and animals. However, Superovulatory PMSG/hCG treatment is known to affect maternal environment, and these effects may result from PMSG/hCG treatment-induced oxidative stress. 2-...
Superovulation induced by exogenous gonadotropin treatment (PMSG/hCG) increases the number of available oocytes in humans and animals. However, Superovulatory PMSG/hCG treatment is known to affect maternal environment, and these effects may result from PMSG/hCG treatment-induced oxidative stress. 2-Cys peroxiredoxins (2-Cys Prxs) act as antioxidant enzymes that protect cells from oxidative stress induced by various exogenous stimuli. Therefore, the objective of this study was to test the hypothesis that repeated PMSG/hCG treatment induces 2-Cys Prx expression and overoxidation in the reproductive tracts of female mice. Immunohistochemistry and western blotting analyses further demonstrated that, after PMSG/hCG treatment, the protein expression levels of 2-Cys Prxs increased most significantly in the ovaries, while that of Prx1 was most affected by PMSG/hCG stimulation in all tissues of the female reproductive tract. Repeated PMSG/hCG treatment eventually leads to 2-Cys Prxs overoxidation in all reproductive organs of female mice, and the abundance of the 2-Cys Prxs-$SO_{2/3}$ proteins reported here supports the hypothesis that repeated superovulation induces strong oxidative stress and damage to the female reproductive tract. Our data suggest that excessive oxidative stress caused by repeated PMSG/hCG stimulation increases 2-Cys Prxs expression and overoxidation in the female reproductive organs. Intracellular 2-Cys Prx therefore plays an important role in maintaining the reproductive organ environment of female mice upon exogenous gonadotropin treatment.
Superovulation induced by exogenous gonadotropin treatment (PMSG/hCG) increases the number of available oocytes in humans and animals. However, Superovulatory PMSG/hCG treatment is known to affect maternal environment, and these effects may result from PMSG/hCG treatment-induced oxidative stress. 2-Cys peroxiredoxins (2-Cys Prxs) act as antioxidant enzymes that protect cells from oxidative stress induced by various exogenous stimuli. Therefore, the objective of this study was to test the hypothesis that repeated PMSG/hCG treatment induces 2-Cys Prx expression and overoxidation in the reproductive tracts of female mice. Immunohistochemistry and western blotting analyses further demonstrated that, after PMSG/hCG treatment, the protein expression levels of 2-Cys Prxs increased most significantly in the ovaries, while that of Prx1 was most affected by PMSG/hCG stimulation in all tissues of the female reproductive tract. Repeated PMSG/hCG treatment eventually leads to 2-Cys Prxs overoxidation in all reproductive organs of female mice, and the abundance of the 2-Cys Prxs-$SO_{2/3}$ proteins reported here supports the hypothesis that repeated superovulation induces strong oxidative stress and damage to the female reproductive tract. Our data suggest that excessive oxidative stress caused by repeated PMSG/hCG stimulation increases 2-Cys Prxs expression and overoxidation in the female reproductive organs. Intracellular 2-Cys Prx therefore plays an important role in maintaining the reproductive organ environment of female mice upon exogenous gonadotropin treatment.
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문제 정의
) in the reproductive tracts of female mice. In this study, it was shown that the histological morphologies of the ovaries and the uteri of mice were affected by repeated PMSG/hCG treatment. A histomorphological assessment by H&E staining showed the increased sizes of PMSG/hCGtreated ovaries, which can be attributed to a dramatic increase in the number of the superovulated follicles stimulated by gonadotropin.
The aim of this study was therefore to assess the effects of exogenous gonadotropin-stimulated superovulation on the reproductive tracts of female mice. We investigated whether repeated PMSG/hCG superovulation treatments induce histomorphological changes in the ovaries, oviducts, and uteri of mice and examined whether intracellular 2-Cys Prx expression and overoxidation (2-Cys Prx-SO2/3) are induced by repeated superovulation.
Gonadotropin is used for ovarian stimulation both in animal experiments on embryogenesis as well as in women for the treatment of infertility (Practice Committee of American Society for Reproductive Medicine, 2008); however, our findings suggest that excess gonadotropin stimulation may cause side effects, specifically damage to reproductive function and the maternal environment. This study provides insight that may improve our understanding of the changes that occur in the female reproductive organs following exogenous gonadotropin use.
제안 방법
To investigate the effects of repetitive superovulation treatments on the histological morphologies of female reproductive tracts in mice, single (1×) or repeated (3×) doses of PMSG/hCG were administered to mice by intraperitoneally (ip) injection.
To investigate whether repeated superovulation affects 2-Cys peroxiredoxins (Prxs) expression and localization in female reproductive organs, the expression of Prx1, 2, and 3 was assessed by immunohistochemistry staining after PMSG/hCG injection. As shown in Fig.
대상 데이터
Female ICR mice (10 weeks of age) were purchased from Hyochang Bio-Science (Korea) and maintained in accordance with the institutional guidelines of the Institutional Animal care and Use Committee of the Korea Research Institute of Bioscience and Biotechnology (KRIBB, Korea). All mice were maintained under a 12-h-dark/light cycle, a temperature at 20-22°C and a humidity of 50-60% with continuous supply of chow and water.
Slides were counterstained with hematoxylin before mounting and then evaluated under Olympus BX51 microscope Olympus). The images were acquired with an Olympus DP 70 camera (Olympus).
데이터처리
Data are presented as the means ± SEM of three or more independent experiments. For group comparisons, one-way ANOVA followed by Newman-Keuls multiple comparison tests were performed using the Prism software package version 4.0 for statistical data analysis (GraphPad Software, Inc.). All experiments were repeated independently at least three times.
성능/효과
Overall, these findings indicate that the expression of the Prx1, Prx2, and Prx3 proteins in ovaries is significantly increased by PMSG/hCG treatment in mice. After PMSG/hCG stimulation, Prx1 expression is further elevated in oviducts and uteri, whereas significant differences in the expression levels of Prx2 and Prx3 in oviducts and uteri between PMSG/hCG-treated and untreated mice were not detected.
In conclusion, our results indicate that repeated PMSG/hCG stimulation induces histomorphological changes in the ovaries and uteri of female mice. Using immunohistochemistry and western blotting, we demonstrated that, among the reproductive tissues assessed, the expression levels of 2-Cys Prxs after PMSG/hCG treatment are most markedly elevated in the ovaries, and that of the 2-Cys Prxs, Prx1 is most affected by PMSG/hCG stimulation in all tissues of the female reproductive tract.
The relative protein expression levels of Prx1, Prx2- SO2/3, and Prx3-SO2/3 were found to be slightly higher in the PMSG/hCG X1 group (p < 0.05 compared with normal) and Prx1-SO2/3 expression was slightly elevated in the PMSG/hCG X3 group (p < 0.05 compared with normal) (Fig. 4B).
This study demonstrates clearly for the first time that repeated PMSG/hCG superovulation treatment causes histomorphological changes, changes in the expression levels of intracellular 2- Cys Prxs (Prx 1-3), as well as overoxidation of 2-Cys Prxs (2- Cys Prxs-SO2/3) in the reproductive tracts of female mice. In this study, it was shown that the histological morphologies of the ovaries and the uteri of mice were affected by repeated PMSG/hCG treatment.
후속연구
Consequently, these results indicate that repeated gonadotropin stimulation adversely affects the histomorphology and environment of the female reproductive tract in mice, with the exception of the oviduct. It is possible that the ovaries and uterine environments of repeatedly superovulated female mice inhibit blastocyst formation, embryo development, and embryo implantation; however, to investigate this possibility, additional studies would need to be conducted to assess the effects of repeated superovulation on embryo formation, development, and implantation.
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