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Mouse Oocyte Microinjection, Maturation and Ploidy Assessment
Published on: July 23, 2011
PKCδ and θ possibly mediate FSH-induced mouse oocyte maturation via NOX-ROS-TACE cascade signaling pathway
Qian Chen1, Wenqiang Zhang1, Hao Ran1
1State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People's Republic of China.
Abstract:
In mammals, gonadotropins stimulate oocyte maturation via the epidermal growth factor (EGF) network, and the protein kinase C (PKC) signaling pathway mediates this process. Tumor necrosis factor-α converting enzyme (TACE) is an important protein responding to PKC activation. However, the detailed signaling cascade between PKC and TACE in follicle-stimulating hormone (FSH)-induced oocyte maturation in vitro remains unclear. In this study, we found that rottlerin (mallotoxin, MTX), the inhibitor of PKC δ and θ, blocked FSH-induced maturation of mouse cumulus-oocyte complexes (COCs) in vitro. We further clarified the relationship between two molecules downstream of PKC δ and θ and TACE in COCs: nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) and its products, reactive oxygen species (ROS). We proved that the respective inhibitors of NOX, ROS and TACE could block FSH-stimulated oocyte maturation dose-dependently, but these inhibitory effects could be reversed partially by amphiregulin (Areg), an EGF family member. Notably, inhibition of PKC δ and θ prevented FSH-induced translocation of two cytosolic components of NOX, p47phox and p67phox, to the plasma membrane in cumulus cells. Moreover, FSH-induced TACE activity in cumulus cells was decreased markedly by inhibition of NOX and ROS. In conclusion, PKC δ and θ possibly mediate FSH-induced meiotic resumption in mouse COCs via NOX-ROS-TACE signaling pathway.
Insights
Protein kinase C delta and theta (PKCδ/θ) mediate FSH-induced mouse oocyte maturation. This occurs through the nicotinamide adenine dinucleotide phosphate oxidase (NOX)-reactive oxygen species (ROS)-tumor necrosis factor-α converting enzyme (TACE) pathway.
Area of Science:
- Reproductive Biology
- Cell Signaling
- Mammalian Oogenesis
Background:
- Gonadotropins, like follicle-stimulating hormone (FSH), trigger oocyte maturation in mammals.
- The epidermal growth factor (EGF) network and protein kinase C (PKC) signaling pathway are crucial mediators.
- The precise signaling cascade linking PKC to tumor necrosis factor-α converting enzyme (TACE) in FSH-induced oocyte maturation is not fully understood.
Purpose of the Study:
- To elucidate the signaling pathway between PKC and TACE in FSH-induced mouse oocyte maturation.
- To investigate the role of PKCδ and PKCθ in this process.
- To identify downstream effectors of PKC involved in mediating oocyte maturation.
Main Methods:
- Used rottlerin (MTX), a PKCδ/θ inhibitor, to assess its effect on FSH-induced maturation of mouse cumulus-oocyte complexes (COCs).
- Investigated the involvement of nicotinamide adenine dinucleotide phosphate oxidase (NOX) and reactive oxygen species (ROS) using specific inhibitors.
- Examined the activity and translocation of NOX components (p47phox, p67phox) and TACE in response to FSH and PKC inhibition.
- Assessed the partial rescue effect of amphiregulin (Areg) on inhibitory treatments.
Main Results:
- Rottlerin (MTX) inhibited FSH-induced maturation of mouse COCs.
- Inhibitors of NOX, ROS, and TACE dose-dependently blocked FSH-stimulated oocyte maturation, with partial reversal by Areg.
- PKCδ/θ inhibition prevented FSH-induced translocation of p47phox and p67phox to the plasma membrane in cumulus cells.
- NOX and ROS inhibition significantly decreased FSH-induced TACE activity.
Conclusions:
- PKCδ and PKCθ are essential for FSH-induced meiotic resumption in mouse COCs.
- The NOX-ROS-TACE signaling pathway is a likely downstream mediator of PKCδ/θ action.
- This pathway plays a critical role in regulating oocyte maturation in response to FSH stimulation.
