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Published on: July 30, 2020
DMBA acts on cumulus cells to desynchronize nuclear and cytoplasmic maturation of pig oocytes
Zhi-Qiang Song1, Xuan Li1, Yan-Kui Wang1
1College of Animal Science and Technology, Northeast Agricultural University, Harbin, 150030, China.
Abstract:
As an environmental pollutant and carcinogen, 7,12-dimethylbenz[a]anthracene (DMBA) can destroy ovarian follicles at all developmental stages in rodents. However, the underlying molecular mechanism remains obscure. In the present study, we aim to address how DMBA affects the in vitro maturation and development of porcine oocytes. We discovered that for 20 μM DMBA-treated cumulus-oocyte complexes (COCs), the rate of oocyte germinal vesicle breakdown (GVBD) was significantly altered, and the extrusion rate of first polar body was increased. Moreover, oocytes from 20 μM DMBA-treated COCs had significant down-regulation of H3K9me3 and H3K27me3, up-regulation of H3K36me3, higher incidence of DNA double strand breaks (DSBs) and early apoptosis. In striking contrast, none of these changes happened to 20 μM DMBA-treated cumulus-denuded oocytes (CDOs). Furthermore, 20 μM DMBA treatment increased the reactive oxygen species (ROS) level, decreased mitochondrial membrane potential (Δ Ψm), and inhibited developmental competence for oocytes from both COC and CDO groups. Collectively, our data indicate DMBA could act on cumulus cells via the gap junction to disturb the synchronization of nuclear and ooplasmic maturation, and reduce the developmental competence of oocytes.
Insights
7,12-dimethylbenz[a]anthracene (DMBA) disrupts porcine oocyte maturation by affecting cumulus cells, leading to altered epigenetic marks, DNA damage, and reduced developmental competence. The mechanism involves gap junction communication disruption.
Area of Science:
- Reproductive Biology
- Environmental Toxicology
- Epigenetics
Background:
- 7,12-dimethylbenz[a]anthracene (DMBA) is an environmental pollutant and carcinogen known to damage ovarian follicles.
- The precise molecular mechanisms by which DMBA affects oocyte development remain largely unknown.
Purpose of the Study:
- To investigate the effects of DMBA on the in vitro maturation and developmental competence of porcine oocytes.
- To elucidate the molecular mechanisms underlying DMBA-induced oocyte damage, focusing on the role of cumulus cells.
Main Methods:
- Porcine cumulus-oocyte complexes (COCs) and cumulus-denuded oocytes (CDOs) were treated with 20 μM DMBA in vitro.
- Evaluated oocyte maturation parameters including germinal vesicle breakdown (GVBD) and first polar body extrusion.
- Assessed epigenetic modifications (H3K9me3, H3K27me3, H3K36me3), DNA double-strand breaks (DSBs), apoptosis, reactive oxygen species (ROS) levels, and mitochondrial membrane potential (ΔΨm).
Main Results:
- DMBA treatment in COCs significantly altered GVBD rates, increased first polar body extrusion, and induced down-regulation of H3K9me3/H3K27me3 and up-regulation of H3K36me3.
- DMBA exposure led to increased DSBs, apoptosis, ROS, and decreased ΔΨm in oocytes from COCs.
- Cumulus-denuded oocytes showed no epigenetic or DNA damage changes, but both COC and CDO groups exhibited reduced developmental competence and increased ROS/decreased ΔΨm.
- DMBA's effects were primarily mediated through cumulus cells via gap junction communication.
Conclusions:
- DMBA impairs porcine oocyte maturation and developmental competence by disrupting the communication between oocytes and cumulus cells.
- The mechanism involves epigenetic alterations, increased oxidative stress, and mitochondrial dysfunction, likely mediated through gap junctions.
- DMBA poses a significant threat to reproductive health by compromising oocyte quality and developmental potential.
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