Effects of differing oocyte-secreted factors during mouse in vitro maturation on subsequent embryo and fetal development

Sudiman, Jaqueline; Ritter, Lesley J.; Feil, D.; Wang, X.; Chan, Karen; Mottershead, David G.; Robertson, David; Thompson, Jeremy G.; Gilchrist, Robert B.

doi:10.1007/s10815-013-0152-5

Cited by 52 publications

(59 citation statements)

References 63 publications

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“…3). These results are entirely consistent with our recent observation that pro-BMP15, but not mature domain BMP15 nor mature domain mouse GDF9, enhances oocyte developmental competence (54,55). It is well established that prodomains of TGF-␤ superfamily growth factors have important roles in protein folding and regulation of bioactivity (56,57).…”

Section: Discussionsupporting

confidence: 92%

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Cumulin, an Oocyte-secreted Heterodimer of the Transforming Growth Factor-β Family, Is a Potent Activator of Granulosa Cells and Improves Oocyte Quality

Mottershead

Sugimura

Al-Musawi

et al. 2015

Journal of Biological Chemistry

151

188

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Background: Cumulin is a newly identified heterodimeric member of the TGF-␤ family. Results: Mature cumulin potently stimulates granulosa cell signaling and function, whereas pro-cumulin promotes oocyte quality. Conclusion: Formation of cumulin and its potent actions are likely to be central to oocyte paracrine signaling and mammalian fecundity. Significance: The discovery of cumulin provides unique opportunities to improve female fertility in mammals.

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Section: Discussionsupporting

confidence: 92%

“…We and others have shown that addition of "native" oocyte-secreted factors (e.g. pro-BMP15 or pro-GDF9) to IVM enhances oocyte quality, having profound effects on embryo development and fetal survival (13,54,55,(61)(62)(63)(64). This study is the first report on the effects of cumulin on oocyte quality.…”

Section: Discussionmentioning

confidence: 63%

Cumulin, an Oocyte-secreted Heterodimer of the Transforming Growth Factor-β Family, Is a Potent Activator of Granulosa Cells and Improves Oocyte Quality

Mottershead

Sugimura

Al-Musawi

et al. 2015

Journal of Biological Chemistry

151

188

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“…Moreover, addition of a purified BMP15 pro-mature complex to IVM medium increases bovine embryo development [14], [38]. By contrast, we have recently shown that addition of the isolated mature homodomains of GDF9 and/or BMP15 (from R&D Systems) has no effect on mouse IVM [39]. No studies to date have directly compared the effect of the form of GDF9 or BMP15 added during IVM on embryo development.…”

Section: Introductionmentioning

confidence: 96%

Bone Morphogenetic Protein 15 in the Pro-Mature Complex Form Enhances Bovine Oocyte Developmental Competence

et al. 2014

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Developmental competence of in vitro matured (IVM) oocytes needs to be improved and this can potentially be achieved by adding recombinant bone morphogenetic protein 15 (BMP15) or growth differentiation factor (GDF9) to IVM. The aim of this study was to determine the effect of a purified pro-mature complex form of recombinant human BMP15 versus the commercially available bioactive forms of BMP15 and GDF9 (both isolated mature regions) during IVM on bovine embryo development and metabolic activity. Bovine cumulus oocyte complexes (COCs) were matured in vitro in control medium or treated with 100 ng/ml pro-mature BMP15, mature BMP15 or mature GDF9 +/− FSH. Metabolic measures of glucose uptake and lactate production from COCs and autofluorescence of NAD(P)H, FAD and GSH were measured in oocytes after IVM. Following in vitro fertilisation and embryo culture, day 8 blastocysts were stained for cell numbers. COCs matured in medium +/− FSH containing pro-mature BMP15 displayed significantly improved blastocyst development (57.7±3.9%, 43.5±4.2%) compared to controls (43.3±2.4%, 28.9±3.7%) and to mature GDF9+FSH (36.1±3.0%). The mature form of BMP15 produced intermediate levels of blastocyst development; not significantly different to control or pro-mature BMP15 levels. Pro-mature BMP15 increased intra-oocyte NAD(P)H, and reduced glutathione (GSH) levels were increased by both forms of BMP15 in the absence of FSH. Exogenous BMP15 in its pro-mature form during IVM provides a functional source of oocyte-secreted factors to improve bovine blastocyst development. This form of BMP15 may prove useful for improving cattle and human artificial reproductive technologies.

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“…Further, being bacterially expressed, this hGDF9 lacks the posttranslational modifications that may be relevant for GDF9 (66,72). Finally, the protein used for the above-mentioned granulosa cell studies consists of only the mature region of the protein, and we have recently shown that the purified mGDF9 mature region is not active in stimulating oocyte developmental competence (40). We have also shown for human BMP15 that the protein needs to be present as the purified pro-mature complex form to stimulate oocyte developmental competence (73).…”

Section: Discussionmentioning

confidence: 99%

Modifications of Human Growth Differentiation Factor 9 to Improve the Generation of Embryos From Low Competence Oocytes

Sugimura

Mueller

et al. 2015

Molecular Endocrinology

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Growth differentiation factor 9 (GDF9) is an oocyte-derived growth factor that plays a critical role in ovarian folliculogenesis and oocyte developmental competence and belongs to the TGF-β family of proteins. Recombinant human GDF9 (hGDF9) is secreted in a latent form, which in the case of the fully processed protein, has the proregion noncovalently associated with the mature region. In this study, we investigated a number of amino acid residues in the mature region of hGDF9 that are different from the corresponding residues in the mouse protein, which is not latent. We designed, expressed, and purified 4 forms of chimeric hGDF9 (M1-M4) that we found to be active in a granulosa cell bioassay. Using a porcine in vitro maturation model with inherent low developmental competence (yielding 10%-20% blastocysts), we tested the ability of the chimeric hGDF9 proteins to improve oocyte maturation and developmental competence. Interestingly, one of the chimeric proteins, M3, was able to significantly increase the level of embryo production using such low competence oocytes. Our molecular modeling studies suggest that in the case of hGDF9 the Gly(391)Arg mutation probably increases receptor binding affinity, thereby creating an active protein for granulosa cells in vitro. However, for an improvement in oocyte developmental competence, a second mutation (Ser(412)Pro), which potentially decreases the affinity of the mature region for the proregion, is also required.

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Effects of differing oocyte-secreted factors during mouse in vitro maturation on subsequent embryo and fetal development

Abstract: This study provides new knowledge on means to improve oocyte quality in vitro which has the potential to significantly aid human infertility treatment and animal embryo production technologies.

Cited by 52 publications

References 63 publications

Cumulin, an Oocyte-secreted Heterodimer of the Transforming Growth Factor-β Family, Is a Potent Activator of Granulosa Cells and Improves Oocyte Quality

Cumulin, an Oocyte-secreted Heterodimer of the Transforming Growth Factor-β Family, Is a Potent Activator of Granulosa Cells and Improves Oocyte Quality

Bone Morphogenetic Protein 15 in the Pro-Mature Complex Form Enhances Bovine Oocyte Developmental Competence

Modifications of Human Growth Differentiation Factor 9 to Improve the Generation of Embryos From Low Competence Oocytes

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