Dataset Information

Molecular forms of BMP15 and GDF9 in mammalian species that differ in litter size.

ABSTRACT: Bone morphogenetic protein (BMP15) and growth differentiation factor (GDF9) are critical for ovarian follicular development and fertility and are associated with litter size in mammals. These proteins initially exist as pre-pro-mature proteins, that are subsequently cleaved into biologically active forms. Thus, the molecular forms of GDF9 and BMP15 may provide the key to understanding the differences in litter size determination in mammals. Herein, we compared GDF9 and BMP15 forms in mammals with high (pigs) and low to moderate (sheep) and low (red deer) ovulation-rate. In all species, oocyte lysates and secretions contained both promature and mature forms of BMP15 and GDF9. Whilst promature and mature GDF9 levels were similar between species, deer produced more BMP15 and exhibited, together with sheep, a higher promature:mature BMP15 ratio. N-linked glycosylation was prominant in proregion and mature GDF9 and in proregion BMP15 of pigs, and present in proregion GDF9 of sheep. There was no evidence of secreted native homo- or hetero-dimers although a GDF9 dimer in red deer oocyte lysate was detected. In summary, GDF9 appeared to be equally important in all species regardless of litter size, whilst BMP15 levels were highest in strict monovulatory species.

SUBMITTER: Swinerd GW

PROVIDER: S-EPMC10725505 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Molecular forms of BMP15 and GDF9 in mammalian species that differ in litter size.

Swinerd Gene W GW Alhussini Abdulaziz A AA Sczelecki Sarah S Heath Derek D Mueller Thomas D TD McNatty Kenneth P KP Pitman Janet L JL

Scientific reports 20231216 1

Bone morphogenetic protein (BMP15) and growth differentiation factor (GDF9) are critical for ovarian follicular development and fertility and are associated with litter size in mammals. These proteins initially exist as pre-pro-mature proteins, that are subsequently cleaved into biologically active forms. Thus, the molecular forms of GDF9 and BMP15 may provide the key to understanding the differences in litter size determination in mammals. Herein, we compared GDF9 and BMP15 forms in mammals wit ...[more]

PMID: 38104237

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Project description:(1) Background: Litter size is one of the most important economic traits of sheep. The FecB locus has been extensively studied due to its significant impact on litter size in Hu sheep, and BMP15 and GDF9 have also been reported as major genes associated with litter size in sheep. This study aimed to identify variants of BMP15 and GDF9 and perform an association analysis of these variants with litter size in the Hu sheep breed. (2) Methods: In this study, exons of the BMP15 and GDF9 genes were fully sequenced to identify polymorphisms in Hu sheep. Population genetic parameters and haplotype frequencies were estimated, and an association analysis between these polymorphic loci and litter size was performed. Additionally, the protein structures of the wild-type and mutated BMP15 and GDF9 genes were predicted. (3) Results: The polymorphisms of the BMP15 and GDF9 genes were investigated within their exon regions, revealing mutations at four previously reported sites: BMP15 c.31_33CTTdel and GDF9 (G2, G3, and G4) in Hu sheep, with no novel variants were detected. Genetic analysis indicated that the GDF9-G3 and GDF9-G4 loci have low polymorphisms, whereas the BMP15 c.31_33CTTdel and the GDF9-G2 locus are moderately polymorphic. The mutation sites in the BMP15 and GDF9 genes were under Hardy-Weinberg equilibrium. Association analysis revealed that the BMP15 c.31_33CTTdel and GDF9 (G2, G3, and G4) mutations are not associated with litter size in Hu sheep. Protein structure prediction indicated that the mutations in BMP15 and GDF9 resulted in alterations to their tertiary structures. (4) Conclusions: In this study, four reported mutations in the BMP15 and GDF9 genes can also be detected in the Hu sheep breed. In these mutations, the G2 and G3 mutations of GDF9 did not alter the amino acid sequence, while the BMP15 c.31_33CTTdel mutation and the GDF9 G4 mutation resulted in protein structure alteration. Furthermore, the BMP15 c.31_33CTTdel mutation and the GDF9 mutations (G2, G3, G4) were associated with an increased tendency in litter size. However, no significant difference was observed (p > 0.05). This study provides valuable insights for improving the lambing performance of Hu sheep.

Project description:Mouse oocytes control cumulus cell metabolic processes that are deficient in the oocytes themselves and this delegation is necessary for oocyte development. Oocyte-derived bone morphogenetic factor 15 (BMP15) and growth differentiation factor 9 (GDF9) appear to be key regulators of follicular development. The effect of these factors on cumulus cell function before the preovulatory surge of luteinizing hormone (LH) was assessed by analysis of the transcriptomes of cumulus cells from wildtype (WT), Bmp15-/-, and Bmp15-/- Gdf9+/- double mutant (DM) mice using microarray analysis. The biological themes associated with the most highly-affected transcripts were identified using bioinformatic approaches, IPA and GenMAPP/MAPPFinder. There were 5,332, 7,640, and 2,651 transcripts identified to be significantly changed in the comparisons of Bmp15-/- vs. WT, DM vs. WT, and DM vs. Bmp15-/- respectively by the criteria of FC (fold change) p <0.01. Among theses changed transcripts, 744 were commonly changed in all three pair-wise comparisons, and hence were considered to be the most highly affected transcripts by mutation of Bmp15 and Gdf9. IPA Analyses revealed that metabolism was the major theme associated with the most highly-changed transcripts: glycolysis and sterol biosynthesis were the two most significantly affected pathways. Most of the transcripts encoding enzymes for sterol biosynthesis were down-regulated in both mutant cumulus cells and in WT cumulus cell after oocytectomy. Similarly, there was a reduction of de novo-synthesized cholesterol in these cumulus cells. This suggests that oocytes regulate cumulus cell metabolism, particularly sterol biosynthesis, by promoting the expression of corresponding transcripts. Furthermore, in WT-mice, Mvk, Pmvk, Fdps, Sqle, Cyp51, Sc4mol, and Ebp, which encode enzymes in the sterol biosynthetic pathway, were found to be expressed robustly in cumulus cells, but expression was barely detectable in oocytes. Levels of de novo-synthesized cholesterol were significantly higher in cumulusâenclosed oocytes than denuded oocytes. These results indicate that mouse oocytes are deficient in their ability to synthesize cholesterol and require cumulus cells to provide them with products of the sterol biosynthetic pathway. Oocyte-derived BMP15 and GDF9 may promote this metabolic pathway in cumulus cells as compensation for their own deficiencies. Experiment Overall Design: Three sets of independent cumulus cell samples were collected for each genotype (wild type, Bmp15-/-, and Bmp15-/-Gdf9+/-) of mice, and were used for the array study as shown below. Experiment Overall Design: Array Genotype Sample Experiment Overall Design: GC_430_2_GES05_0161_033105_1.CEL WT 1 Experiment Overall Design: GC_430_2_GES05_0162_033105_1.CEL WT 2 Experiment Overall Design: GC_430_2_GES05_0163_033105_1.CEL WT 3 Experiment Overall Design: GC_430_2_GES05_0164_033105_1.CEL Bmp15-/- 4 Experiment Overall Design: GC_430_2_GES05_0165_033105_1.CEL Bmp15-/- 5 Experiment Overall Design: GC_430_2_GES05_0166_033105_1.CEL Bmp15-/- 6 Experiment Overall Design: GC_430_2_GES05_0167_033105_1.CEL DM 7 Experiment Overall Design: GC_430_2_GES05_0168_033105_1.CEL DM 8 Experiment Overall Design: GC_430_2_GES05_0169_033105_1.CEL DM 9

Dataset Information

Molecular forms of BMP15 and GDF9 in mammalian species that differ in litter size.

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Molecular forms of BMP15 and GDF9 in mammalian species that differ in litter size.

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