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Regulation of the Activin-Inhibin-Follistatin System by Bone Morphogenetic Proteins in the Zebrafish Ovary
Li, Cheuk Wun1; Ge, Wei1,2

In the zebrafish, the dynamic expression of the activin-inhibin-follistatin system during folliculogenesis and its exclusive localization (except follistatin) in follicle cells suggests that the system plays important roles in follicle development and that its expression is subject to tight controls, probably by external factors including those derived from the oocyte. We have previously identified zebrafish bone morphogenetic proteins (BMPs) as oocyte factors that may act on follicle cells; however, the targets of BMPs in the follicle cells remain unknown. Considering their spatiotemporal expression in the follicle, we hypothesized that members of the activin-inhibin-follistatin system in follicle cells could be potential target genes of BMPs. In the present study, we developed a novel coculture system to co-incubate zebrafish bone morphogenetic protein 2b or 4 (zfBMP2b/4)-producing Chinese hamster ovary (CHO) cells with zebrafish follicle cells. During incubation, the zfBMPs secreted from the CHO cells would act directly on the follicle cells in a paracrine manner. Our results showed that all activin beta subunits (inhbaa, inhbab, and inhbb) were down-regulated by both zfBMP2b and zfBMP4, while follistatin (fst, an activin-binding protein) and inhibin alpha (inha, an activin antagonist) were significantly up-regulated. The specificity of bone morphogenetic protein (BMP) actions was confirmed by short interfering RNA knockdown of zfBMP4 expression in the CHO cells. The robust response of inha to zfBMPs, together with our previous observation that inha expression surged at the full-grown stage prior to oocyte maturation, led us to hypothesize that the full-grown oocyte may signal upper levels of the hypothalamic-pituitary-gonadal axis its readiness to mature by releasing BMPs, which in turn stimulate inhibin production. As an ovarian hormone and activin antagonist, inhibin may suppress the action of activin in the pituitary to reduce follicle-stimulating hormone but increase luteinizing hormone (LH) biosynthesis. Meanwhile, by increasing the local follistatin level and reducing the activin production, BMPs could help prevent precocious maturation before preovulatory LH surge.

KeywordActivin Bone Morphogenetic Proteins Follistatin Inhibin Ovary Zebrafish
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Indexed BySCIE
WOS Research AreaReproductive Biology
WOS SubjectReproductive Biology
WOS IDWOS:000325007200006
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Cited Times [WOS]:8   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Corresponding AuthorGe, Wei
Affiliation1.School of Life Sciences and Centre for Cell and Developmental Biology, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China
2.Faculty of Health Sciences, University of Macau, Taipa, Macau, China
Corresponding Author AffilicationFaculty of Health Sciences
Recommended Citation
GB/T 7714
Li, Cheuk Wun,Ge, Wei. Regulation of the Activin-Inhibin-Follistatin System by Bone Morphogenetic Proteins in the Zebrafish Ovary[J]. BIOLOGY OF REPRODUCTION,2013,89(3):1-10.
APA Li, Cheuk Wun,&Ge, Wei.(2013).Regulation of the Activin-Inhibin-Follistatin System by Bone Morphogenetic Proteins in the Zebrafish Ovary.BIOLOGY OF REPRODUCTION,89(3),1-10.
MLA Li, Cheuk Wun,et al."Regulation of the Activin-Inhibin-Follistatin System by Bone Morphogenetic Proteins in the Zebrafish Ovary".BIOLOGY OF REPRODUCTION 89.3(2013):1-10.
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