Podophyllotoxin affects porcine oocyte maturation by inducing oxidative stress-mediated early apoptosis

Jiang, Wen-Jie; Hu, Linlin; Ren, Yanping; Xiang, Lei; Luo, X.J.; Li, Yinghua; Xu, Yong‐Nan

doi:10.1016/j.toxicon.2020.01.006

Cited by 22 publications

(15 citation statements)

References 20 publications

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“…Our results showed that the disturbation on the embryo development increased with the higher PPT concentration. Studies have shown that PPT can affect oocyte maturation by destroying the structure of the spindle (Jiang et al, 2020). Combined with our preliminary results, it suggested that PPT was toxic to both oocyte and embryo development.…”

Section: Discussionsupporting

confidence: 70%

“…When cells suffer from stress, low levels of ROS are beneficial, which promote adaptation to stress through signaling; however, high levels of ROS are harmful and promote oxidative stress in cells (Scialo et al, 2017). PPT has been shown to cause oxidative stress and apoptosis in porcine oocytes (Jiang et al, 2020). Mycotoxins, such as AFB1, deoxynivalenol, and HT-2 toxins, could also cause oxidative stress in oocytes and other cell types (Yang et al, 2014;Zhang et al, 2016;Lu et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…The PPT was dissolved in DMSO (concentrated at 10 mM) and diluted in M16 medium to produce a final concentration of 0.5, 1, and 2 nM, respectively. The concentration was due to the previous studies on the PPT (Jiang et al, 2020). And, the zygotes were continuously exposed to PPT until we collected for analysis.…”

Section: Embryo Culture and Ppt Treatmentmentioning

confidence: 99%

“…PPT also has reproductive toxicity: it is shown to inhibit rat sperm maturation and fertility by promoting the apoptosis of epididymal epithelial cells (Xie et al, 2017). For female animals, PPT can affect oocyte maturation by causing porcine oocytes to undergo oxidative stress and apoptosis (Jiang et al, 2020). However, until now, the toxic effects of PPT on early embryo quality have not been reported.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Podophyllotoxin Exposure Causes Spindle Defects and DNA Damage-Induced Apoptosis in Mouse Fertilized Oocytes and Early Embryos

Liao

Wei

et al. 2020

Front. Cell Dev. Biol.

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Podophyllotoxin (PPT) is a kind of lignans extracted from the roots and stems of the genus Podophyllum from the tiller family, and it has been widely used in the treatment of condyloma acuminatum, multiple superficial epithelioma in the clinics. However, PPT has been reported to be toxic and can cause liver defects and other organ poisoning. In addition, emerging evidences also indicate that PPT has reproductive toxicity and causes female reproduction disorders. In this study, we used fertilized oocytes and tried to explore the effects of PPT on the early embryonic development with the mouse model. The results showed that exposure to PPT had negative effects on the cleavage of zygotes. Further analysis indicated that PPT could disrupt the organization of spindle and chromosome arrangement at the metaphase of first cleavage. We also found that PPT exposure to the zygotes induced excessive reactive oxygen species (ROS), suggesting the occurrence of oxidative stress. Moreover, in the PPT-exposed embryos, there was positive γH2A.X and Annexin-V signals, indicating that PPT induced embryonic DNA damage and early apoptosis. In conclusion, our results suggested that PPT could affect spindle formation and chromosome alignment during the first cleavage of mouse embryos, and its exposure induced DNA damage-mediated oxidative stress which eventually led to embryonic apoptosis, indicating the toxic effects of PPT on the early embryo development.

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Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Section: Embryo Culture and Ppt Treatmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Podophyllotoxin Exposure Causes Spindle Defects and DNA Damage-Induced Apoptosis in Mouse Fertilized Oocytes and Early Embryos

Liao

Wei

et al. 2020

Front. Cell Dev. Biol.

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“…Since oxidative stress and apoptosis in oocytes can subsequently influence embryonic development, fetal growth, and the health status of offspring [23,39,40], we sought to study the effect of NAM on the developmental competence of bovine embryos. Checking day-4 total cleavage and 8-16 cell stage embryos, as well as day-7 and day-8 blastocyst development rates, showed the detrimental effects of high NAM concentrations.…”

Section: Discussionmentioning

confidence: 99%

Nicotinamide Supplementation during the In Vitro Maturation of Oocytes Improves the Developmental Competence of Preimplantation Embryos: Potential Link to SIRT1/AKT Signaling

Sheikh

Mesalam

Idrees

et al. 2020

Cells

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Nicotinamide (NAM), the amide form of vitamin B3, plays pivotal roles in regulating various cellular processes including energy production and maintenance of genomic stability. The current study aimed at deciphering the effect of NAM, when administered during in vitro maturation (IVM), on the developmental competence of bovine preimplantation embryos. Our results showed that low NAM concentrations reduced the oxidative stress and improved mitochondrial profile, total cleavage and 8–16 cell stage embryo development whereas the opposite profile was observed upon exposure to high NAM concentrations (10 mM onward). Remarkably, the hatching rates of day-7 and day-8 blastocysts were significantly improved under 0.1 mM NAM treatment. Using RT-qPCR and immunofluorescence, the autophagy-related (Beclin-1 (BECN1), LC3B, and ATG5) and the apoptotic (Caspases; CASP3 and 9) markers were upregulated in oocytes exposed to high NAM concentration (40 mM), whereas only CASP3 was affected, downregulated, following 0.1 mM treatment. Additionally, the number of cells per blastocyst and the levels of SIRT1, PI3K, AKT, and mTOR were higher, while the inner cell mass-specific transcription factors GATA6, SOX2, and OCT4 were more abundant, in day-8 embryos of NAM-treated group. Taken together, to our knowledge, this is the first study reporting that administration of low NAM concentrations during IVM can ameliorate the developmental competence of embryos through the potential regulation of oxidative stress, apoptosis, and SIRT1/AKT signaling.

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Oxidative stress in oocyte aging and female reproduction

Wang

Tang

Wang

et al. 2021

Journal Cellular Physiology

204

112

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In a healthy body, reactive oxygen species (ROS) and antioxidants remain balanced. When the balance is broken toward an overabundance of ROS, oxidative stress appears and may lead to oocyte aging. Oocyte aging is mainly reflected as the gradual decrease of oocyte quantity and quality. Here, we aim to review the relationship between oxidative stress and oocyte aging. First, we introduced that the defective mitochondria, the age‐related ovarian aging, the repeated ovulation, and the high‐oxygen environment were the ovarian sources of ROS in vivo and in vitro. And we also introduced other sources of ROS accumulation in ovaries, such as overweight and unhealthy lifestyles. Then, we figured that oxidative stress may act as the “initiator” for oocyte aging and reproductive pathology, which specifically causes follicular abnormally atresia, abnormal meiosis, lower fertilization rate, delayed embryonic development, and reproductive disease, including polycystic ovary syndrome and ovary endometriosis cyst. Finally, we discussed current strategies for delaying oocyte aging. We introduced three autophagy antioxidant pathways like Beclin‐VPS34‐Atg14, adenosine 5‘‐monophosphate (AMP)‐activated protein kinase/mammalian target of rapamycin (AMPK/mTOR), and p62‐Keap1‐Nrf2. And we also describe the different antioxidants used to combat oocyte aging. In addition, the hypoxic (5% O2) culture environment for oocytes avoiding oxidative stress in vitro. So, this review not only contribute to our general understanding of oxidative stress and oocyte aging but also lay the foundations for the therapies to treat premature ovarian failure and oocyte aging in women.

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Podophyllotoxin affects porcine oocyte maturation by inducing oxidative stress-mediated early apoptosis

Cited by 22 publications

References 20 publications

Podophyllotoxin Exposure Causes Spindle Defects and DNA Damage-Induced Apoptosis in Mouse Fertilized Oocytes and Early Embryos

Podophyllotoxin Exposure Causes Spindle Defects and DNA Damage-Induced Apoptosis in Mouse Fertilized Oocytes and Early Embryos

Nicotinamide Supplementation during the In Vitro Maturation of Oocytes Improves the Developmental Competence of Preimplantation Embryos: Potential Link to SIRT1/AKT Signaling

Oxidative stress in oocyte aging and female reproduction

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