Expression Analysis of the Prolific Candidate Genes, BMPR1B, BMP15, and GDF9 in Small Tail Han Ewes with Three Fecundity (FecB Gene) Genotypes.
Ontology highlight
ABSTRACT:
SUBMITTER: Tang J
PROVIDER: S-EPMC6210785 | biostudies-literature | 2018 Sep
REPOSITORIES: biostudies-literature
Publications
Expression Analysis of the Prolific Candidate Genes, <i>BMPR1B</i>, <i>BMP15,</i> and <i>GDF9</i> in Small Tail Han Ewes with Three Fecundity (<i>FecB</i> Gene) Genotypes.
Tang Jishun J Hu Wenping W Di Ran R Liu Qiuyue Q Wang Xiangyu X Zhang Xiaosheng X Zhang Jinlong J Chu Mingxing M
Animals : an open access journal from MDPI 20180928 10
The expression characteristics of the prolific candidate genes, <i>BMPR1B</i>, <i>BMP15</i>, and <i>GDF9</i>, in the major visceral organs and hypothalamic⁻pituitary⁻gonadal (HPG) axis tissues of three <i>FecB</i> genotypes (FecB BB, FecB B+, and FecB ++) were explored in STH ewes using RT-PCR and qPCR. The results were as follows, <i>BMPR1B</i> was expressed in all FecB BB genotype (Han BB) tissues, and <i>GDF9</i> was expressed in all selected tissues, but <i>BMP15</i> was specifically express ...[more]
Similar Datasets
Project description:The litter size and ovulation rate are different among ewes of different FecB genotypes in Small Tail Han sheep. These variants in reproductive phenotypes may be regulated by hormones released by the hypothalamic-pituitary-ovarian axis. However, there have been few reports on the hypothalamus regarding regulating an increase in ovulation in sheep with FecB mutation at different estrous stages. Thus, we examined the abundance of hypothalamus tissue protein profiles of six FecB mutant homozygous (BB) and six wild-type (WW) ewes at the luteal and follicular phases. We determined this abundance by tandem mass tag-based quantitative analysis and parallel reaction monitoring methods. Furthermore, an integrated proteotranscriptomic analysis was performed by the Data Integration Analysis for Biomarker discovery using the latent variable approaches for Omics studies (DIABLO) framework to examine biological processes and pathway alterations by the FecB mutant. The abundance of 154 proteins was different between the two estrous stages. Growth hormone and prolactin were particularly enriched in the neuroactive ligand-receptor interactions, the prolactin signaling pathway, and the PI3K-Akt signaling pathway which are related to hypothalamic function and reproduction. We combined proteome and transcriptome data from different estrous stages and genotypes. There is a high correlation (Pearson correlation coefficient = 0.99) between the two datasets in the first two components. We applied the traditional single-omic multivariate approach to obtain differentially abundant proteins and differentially expressed genes. The major fertility related biomarkers were selected using the two approaches mentioned above. Several key pathways (GABAergic synapse, neuroactive ligand-receptor interaction, estrogen and MAPK signaling pathways) were enriched, which are central to gonadotrophin-releasing hormone (GnRH) secretion and reproduction. A higher level of gamma-aminobutyric acid type A receptor subunit alpha1 (GABRA1) and gamma-aminobutyric acid type A receptor subunit beta2 (GABRB2) expression was observed in BB ewes as compared to WW ewes. This finding suggested that a greater production of GnRH during follicular development in BB ewes may explain the higher mature follicle number in mutant ewes. FKBP prolyl isomerase 1A (FKBP1A), which was a major feature factor in the proteome selected by DIABLO, was an important switch for activating the transforming growth factor beta (TGFβ) pathway, and its expression was higher in the WW ewes than in the BB ewes. We suggest that BB sheep maintain TGFβ pathway activity by reducing FKBP1A protein abundance. This innovative data integration in the hypothalamus may provide fresh insight into the mechanisms by which the FecB mutation affects sheep fertility, while providing novel biomarkers related to reproductive endocrinology in sheep breeding.
| S-EPMC9856028 | biostudies-literature
Project description:This study was carried out to determine the presence of polymorphisms in genes affecting litter size. The SNPs in bone morphogenetic protein receptor type 1B (BMPR1B), bone morphogenetic protein 15 (BMP15), and growth differentiation factor 9 (GDF9) genes were detected in 60 uniparous and 60 multiparous ewes from Ramlıç and Dağlıç breeds. The ewes are maintained in nine public herds at the breeding station of the Afyonkarahisar Sheep and Goats Breeders' Association and lambed in two consecutive breeding seasons. PCR and DNA sequencing analyses were conducted, and 36, 4, and 11 SNPs in Ramlıç and 40, 3, and 11 SNPs in Dağlıç were detected in BMPR1B, BMP15, and GDF9 genes, respectively. A total of 16 SNPs in Ramlıç and 10 SNPs in Dağlıç breeds for three genes were found to be significant ( P<0.05 ). The resulting analyses showed that four SNPs (g.49496G>A, c.1658A>C, c.2037C>T, c.2053C>T) of the BMPR1B gene and one deletion mutation (c.28_30delCTT) in the BMP15 gene of the Ramlıç breed as well as five SNPs (c.1487C>A, c.2492C>T, c.2523G>A, c.2880A>G, and c.2763G>A) of the BMPR1B gene of the Dağlıç breed have significant positive regression coefficients in the desired direction of the rare allele. The observed mutations have potential to be used as genetic markers in the selection of prolific animals for both breeds.
| S-EPMC8209503 | biostudies-literature
Project description:PURPOSE:To identify genetic variation associated to premature ovarian insufficiency (POI). METHODS:A total of 74 women with POI (group POI), 45 women with increased FSH levels (group high FSH), and 88 controls (non-POI) were studied. Genotyping of BMP15:c.-9C>G (rs3810682), BMP15:c.328+905A>G (rs3897937), and BMP15:c.852C>T (rs17003221); and GDF9:c.134-694G>A (rs4705974), GDF9:c.-31-951G>A (rs11748063), GDF9:c.-152G>C (rs30177), and GDF9:g.1073C>T (rs803224) was performed by the TaqMan methodology. Chi-square and Fisher's exact tests were performed to evaluate the distribution of genotypes, alleles, odds ratio, and the Hardy-Weinberg equilibrium of each variation. Haplotype analysis was performed for each gene considering the case and control groups. Bonferroni's correction was applied to chi-square and Fisher's exact test data, and p values <?0.007 for genotypes and alleles and <?0.006 for haplotypes were considered significant. RESULTS:It was observed a statistically significant difference in genotype distribution of BMP15:c.852C>T between group POI and controls (p?<?0.001). TT and TC genotypes were more frequently observed in group POI. Genotype distribution in case group POI, however, was not in the Hardy-Weinberg equilibrium, due to the increased number of heterozygotes in the sample. Concerning GDF9, no association was found among the studied genetic variants and POI or high FSH groups. CONCLUSION:It is concluded from the present study that the genotypes CT and TT from BMP15:c.852C>T variation may be risk factors for the development of POI.
| S-EPMC6823326 | biostudies-literature
Project description:The Booroola fecundity gene (FecB) has a mutation that was found to increase the ovulation rate and litter size in Booroola Merino sheep. This mutation is also associated with the fecundity of small-tail han (STH) sheep, an important maternal breed used to produce hybrid offspring for mutton production in China. Previous research showed that the FecB gene affects reproduction in STH sheep, based on litter size records. However, the effects of this gene on estrus, ovulation, and endocrine characteristics in these sheep remain unclear. Here, we analyzed the traits mentioned earlier and compared them among the three FecB genotypes of STH ewes using estrus synchronization. Overall, 53 pluriparous ewes were selected from among 890 STH ewes and subjected to FecB genotyping for experiments to characterize estrous and ovulation rates. FecB heterozygous (+B) ewes presented an earlier onset of estrus (42.9 ± 2.2 h) and a shorter estrous cycle (17.2 ± 0.2 days) (P ≤ 0.05). The ovulation rates increased with the increasing copy number of the B allele (P ≤ 0.01). Ovulation time showed no significant differences among the three FecB genotypes. The serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone, estrogen (E2), and progesterone (P4) were measured in 19 of the ewes. Serum concentrations of E2 and FSH dramatically varied around the time of behavioral estrus. In FecB mutant homozygous (BB) ewes, E2 concentration had two peaks, which were higher (P ≤ 0.05) than those of ++ genotypes. FSH concentration of BB ewes was higher (P ≤ 0.05) than that of the ++ ewes just after estrus. The expression of the estrogen receptor 1 (ESR1) gene in the +B genotype was higher than in the other genotypes. Based on the data for the reproductive performance of STH ewes with the three FecB genotypes, our study suggests that the development of follicles in ewes with the B allele is dependent on the response to FSH regulated by E2 in the early stage. +B ewes, exhibiting moderate ovulation and litter size and a shorter estrous cycle, can be highly recommended in sheep crossbreeding systems for commercial mutton production. Moreover, this study provides useful information to conserve better and use the genetic resources of STH sheep in China.
| S-EPMC8646036 | biostudies-literature
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
2008-06-15 | E-GEOD-7225 | biostudies-arrayexpress
Project description:Small-tailed Han sheep, with different FecB genotypes, manifest distinct ovulation rates and fecundities, which are due to differences in reproductive hormones secreted by the hypothalamic-pituitary-ovarian axis. Nevertheless, the function of the hypothalamus against a FecB mutant background on increasing ovulation rate is rarely reported. Therefore, we determined the expression profiles of hypothalamus tissue collected from six wild-type (WW) and six FecB mutant homozygous (BB) ewes at the follicular and luteal phases by whole-transcriptome sequencing. We identified 53 differentially expressed mRNAs (DEGs) and 40 differentially expressed long non-coding RNAs (DELs) between the two estrus states. Functional annotation analysis revealed that one of the DEGs, PRL, was particularly enriched in the hypothalamic function, hormone-related, and reproductive pathways. The lncRNA-target gene interaction networks and KEGG analysis in combination suggest that the lncRNAs LINC-676 and WNT3-AS cis-acting on DRD2 and WNT9B in different phases may induce gonadotropin-releasing hormone (GnRH) secretion. Furthermore, there were differences of regulatory elements and WNT gene family members involved in the follicular-luteal transition in the reproductive process between wild-type (WNT7A) and FecB mutant sheep (WNT9B). We combined the DEG and DEL data sets screened from different estrus states and genotypes. The overlap of these two sets was identified to select the mRNAs and lncRNAs that have major effects on ovulation. Among the overlapping molecules, seven DEGs and four DELs were involved in the follicular-luteal transition regulated by FecB mutation. Functional annotation analysis showed that two DEGs (FKBP5 and KITLG) were enriched in melanogenesis, oxytocin, and GnRH secretion. LINC-219386 and IGF2-AS were highly expressed in the BB ewes compared with WW ewes, modulating their target genes (DMXL2 and IGF2) to produce more GnRH during follicular development, which explains why mutated ewes produced more mature follicles. These results from expression profiling of the hypothalamus with the FecB mutation at different estrus states provide new insights into how the hypothalamus regulates ovulation under the effect of the FecB mutation.
| S-EPMC8172604 | biostudies-literature
Project description:This paper concerns the likely origin of three mutations with large effects on ovulation rate identified in the Belclare and Cambridge sheep breeds; two in the BMP15 gene (FecX(G) and FecX(B)) and the third (FecG(H)) in GDF9. All three mutations segregate in Belclare sheep while one, FecX(B), has not been found in the Cambridge. Both Belclare and Cambridge breeds are relatively recently developed composites that have common ancestry through the use of genetic material from the Finnish Landrace and Lleyn breeds. The development of both composites also involved major contributions from exceptionally prolific ewes screened from flocks in Ireland (Belclare) and Britain (Cambridge) during the 1960s. The objective of the current study was to establish the likely origin of the mutations (FecX(G), FecX(B) and FecG(H)) through analysis of DNA from Finnish Landrace and Lleyn sheep, and Galway and Texel breeds which contributed to the development of the Belclare breed. Ewes with exceptionally high prolificacy (hyper-prolific ewes) in current flocks on Irish farms were identified to simulate the screening of ewes from Irish flocks in the 1960s. DNA was obtained from: prolific ewes in extant flocks of Lleyn sheep (n = 44) on the Lleyn peninsula in Wales; hyper-prolific ewes (n = 41); prolific Galway (n = 41) ewes; Finnish Landrace (n = 124) and Texel (n = 19) ewes. The FecX(G) mutation was identified in Lleyn but not in Finnish Landrace, Galway or Texel sheep; FecX(B) was only found among the hyper-prolific ewes. The FecG(H) mutation was identified in the sample of Lleyn sheep. It was concluded from these findings that the Lleyn breed was the most likely source of the FecX(G) and FecG(H) mutations in Belclare and Cambridge sheep and that the FecX(B) mutation came from the High Fertility line that was developed using prolific ewes selected from commercial flocks in Ireland in the 1960's and subsequently used in the genesis of the Belclare.
| S-EPMC3534649 | biostudies-literature
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 cumulus–enclosed 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. Keywords: Gdf9, Bmp15, cumulus cells, transcriptome, metabolism, sterol biosynthesis, genotype comparison, microarray, ingenuity pathways analyses.
2007-10-22 | GSE7225 | GEO
Project description:The Markhoz is a local goat breed in the Kurdistan region of Iran. The mohair obtained from these animals plays an important cultural role and is used for making local clothes in the Kurdistan region. This breed is a low-fecundity local goat, and searching for genes associated with fertility of these goats is important for their breeding. Moreover, this research is complementary to prior studies of candidate genes associated with fertility. The growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are attractive candidates expressed by the oocyte and are associated with increased ovulation rate in sheep. However, there are no reports on single nucleotide polymorphisms associated with fertility of Markhoz goats. Hence, we studied these candidate genes and found two novel mutations (g.233C > A and g.755T > G) in GDF9 exon I and in BMP15 exon II, respectively. Furthermore, we investigated their association with prolificacy. These nucleotide changes are detectable with the PCR-RFLP method and can be used in the screening for highly fecund goats. Both of the mutations significantly increased litter size in heterozygote form for BMP15 and homozygote form for GDF9 in this goat breed. Homozygote females for the BMP15 mutation were not identified in the Markhoz breed, which is similar to the situation found in Belclare sheep, small-tailed Han sheep, and Jining Grey goats.
| S-EPMC6853135 | biostudies-literature
Project description:Background The suggested effects of the oocyte secreted GDF9 and BMP15 growth factors on oocyte maturation are currently based on recombinant proteins, and little is known about native GDF9 and BMP15 in humans. Methods Human immature cumulus-oocyte complexes (COCs) obtained in connection with ovarian tissue cryopreservation (OTC) underwent in vitro maturation (IVM). Oocyte-produced GDF9 and BMP15 were detected in COCs using immunofluorescence, and in fresh GV oocytes and in GV and MII oocytes after IVM by western blot. Concentrations of GDF9, BMP15 homodimers, and GDF9/BMP15 heterodimer in spent media after IVM were measured by ELISA. The relative expression of seven genes from the GDF9 and BMP15 signaling pathways (BMPR2, ALK5, ALK6, SMAD1, SMAD2, SMAD3, and SMAD5) was evaluated in fresh cumulus cells (before IVM) and in cumulus cells from GV and MII oocytes after IVM by RT-qPCR. Results We detected native pro-mature GDF9 and BMP15 in human oocytes with molecular weights (Mw) of 47 kDa and 43 kDa, respectively. Concentrations of GDF9 and BMP15 in spent media after IVM were detected in 99% and 64% of the samples, respectively. The GDF9/BMP15 heterodimer was detected in 76% of the samples. Overall, the concentration of GDF9 was approximately 10-times higher than BMP15. The concentrations of both GDF9 and BMP15 were significantly lower in spent medium from MII oocytes than in media from oocytes that remained at the GV stage. Concentrations of the GDF9/BMP15 heterodimer did not differ between GV and MII oocytes. Furthermore, BMPR2, SMAD3, and SMAD5 were significantly upregulated in cumulus cells from MII oocytes, indicating that both GDF9 and BMP15 signaling were active during oocyte meiotic resumption in vitro. Conclusion These data suggest that the driving mechanisms for oocyte nuclear maturation may involve both GDF9 and BMP15 homodimers, while the role of the GDF9/BMP15 heterodimer is questionable. Supplementary Information The online version contains supplementary material available at 10.1186/s12958-022-01000-6.
| S-EPMC9389727 | biostudies-literature