卵子與卵丘細胞間牽涉複雜paracrine

卵子與卵丘細胞之間牽涉到複雜之交互作用與paracrine
進一步影響到卵子與胚胎之品質

http://humupd.oxfordjournals.org/content/14/2/159.full

Figure 3:

Molecular basis of oocyte–CC paracrine signaling

Details of the molecules mediating oocyte paracrine signaling to CCs are still emerging; however, TGFβ superfamily signaling is central to this communication axis. Key OSFs include GDF9, BMP15 and possibly BMP6. GCs and CCs express a large compliment of TGFβ superfamily receptors, co-receptors and intracellular signal transducer molecules (SMAD). BMPRII is the critical type-II receptor utilized by all three OSF ligands, although BMP6 also binds ActRIIA. GDF9 binding BMPRII/ALK5 leads to activation of ALK5 which in turn phosphorylates SMAD two-three. SMAD two-three associates with the common SMAD4 and then this complex translocates to the nucleus to interact with specific DNA motifs and transcriptional regulators, leading to expression of target genes. BMP15 and BMP6 also bind BMPRII; however, recruitment and activation of ALK6 leads to signaling through the BMP pathway mediated by activated SMAD1/5/8. OSFs also appear to activate the MAPK pathway in CCs, although the signaling cascade is currently unclear. GDF9, growth-differentiation factor 9; BMP15, bone morphogenetic protein 15; BMPRII, bone morphogenetic protein receptor type-II; ALK, activin receptor-like kinase; TGFβ, transforming growth factor β; MAPK, mitogen-activated protein kinase; OSF, oocyte-secreted factor; CC, cumulus cell

Figure 7:

OSF regulation of CC function and oocyte quality

Model depicting oocyte–CC interactions and their impact on subsequent oocyte developmental potential. An oocyte–somatic cell regulatory loop exists, whereby oocytes and CCs regulate each others functions by paracrine and gap-junctional communication. Oocytes secrete soluble growth factors, notably GDF9 and BMP15 and probably others, that lead to the activation of SMAD two-three and MAPK signaling in CCs, which in turn regulate a multitude of CC gene expression and key CC functions. Appropriate CC function and maintenance of the COC microenvironment is dependent on OSFs. In conjunction with maternal signals such as FSH and EGF, CCs pass regulatory growth factors and small metabolites back to the oocyte via paracrine and gap-junctional signaling. This bidirectional CC–oocyte communication loop appears to regulate unknown processes in the oocyte that improves its quality, as assessed by improved developmental potential. CC, cumulus cell; COC, cumulus–oocyte complex; OSF, oocyte-secreted factor; GDF9, growth-differentiation factor 9; BMP15, bone morphogenetic protein 15; EGF, epidermal growth factor. MAPK, mitogen-activated protein kinase