| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-153 |
Sentence |
denotes |
Cumulin, an Oocyte-secreted Heterodimer of the Transforming Growth Factor-β Family, Is a Potent Activator of Granulosa Cells and Improves Oocyte Quality. |
| T2 |
154-423 |
Sentence |
denotes |
Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are oocyte-specific growth factors with central roles in mammalian reproduction, regulating species-specific fecundity, ovarian follicular somatic cell differentiation, and oocyte quality. |
| T3 |
424-524 |
Sentence |
denotes |
In the human, GDF9 is produced in a latent form, the mechanism of activation being an open question. |
| T4 |
525-704 |
Sentence |
denotes |
Here, we produced a range of recombinant GDF9 and BMP15 variants, examined their in silico and physical interactions and their effects on ovarian granulosa cells (GC) and oocytes. |
| T5 |
705-856 |
Sentence |
denotes |
We found that the potent synergistic actions of GDF9 and BMP15 on GC can be attributed to the formation of a heterodimer, which we have termed cumulin. |
| T6 |
857-1011 |
Sentence |
denotes |
Structural modeling of cumulin revealed a dimerization interface identical to homodimeric GDF9 and BMP15, indicating likely formation of a stable complex. |
| T7 |
1012-1158 |
Sentence |
denotes |
This was confirmed by generation of recombinant heterodimeric complexes of pro/mature domains (pro-cumulin) and covalent mature domains (cumulin). |
| T8 |
1159-1401 |
Sentence |
denotes |
Both pro-cumulin and cumulin exhibited highly potent bioactivity on GC, activating both SMAD2/3 and SMAD1/5/8 signaling pathways and promoting proliferation and expression of a set of genes associated with oocyte-regulated GC differentiation. |
| T9 |
1402-1491 |
Sentence |
denotes |
Cumulin was more potent than pro-cumulin, pro-GDF9, pro-BMP15, or the two combined on GC. |
| T10 |
1492-1678 |
Sentence |
denotes |
However, on cumulus-oocyte complexes, pro-cumulin was more effective than all other growth factors at notably improving oocyte quality as assessed by subsequent day 7 embryo development. |
| T11 |
1679-1805 |
Sentence |
denotes |
Our results support a model of activation for human GDF9 dependent on cumulin formation through heterodimerization with BMP15. |
| T12 |
1806-1902 |
Sentence |
denotes |
Oocyte-secreted cumulin is likely to be a central regulator of fertility in mono-ovular mammals. |
