Differential expression of BMP/SMAD signaling and ovarian-associated genes in the granulosa cells of FecB introgressed GMM sheep

Kumar, Satish; Rajput, Pradeep Kumar; Bahire, S.V.; Jyotsana, Basanti; Kumar, Vijay; Kumar, Davendra

doi:10.1080/19396368.2019.1695977

Cited by 10 publications

(7 citation statements)

References 77 publications

(97 reference statements)

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“…BMPs also serve a critical role in maintaining adult tissue homeostasis, including preservation, vascular remodeling, and the fracture repair [ 53 ]. Any deficit in their production or function mostly results in a visible abnormalities or severe diseases in the tissues [ 54 ]. This study examined the functional implications with a functional assay that may be the most effective technique.…”

Section: Discussionmentioning

confidence: 99%

Computational Insights into the Structural and Functional Impacts of nsSNPs of Bone Morphogenetic Proteins

Ahmad

Ijaz

Afzal

et al. 2022

BioMed Research International

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BMPs (bone morphogenetic proteins) are multipurpose (transforming growth factor)TGF-superfamily released cytokines. These glycoproteins, acting as disulfide-linked homo- or heterodimers, are highly potent regulators of bone and cartilage production and repair, cell proliferation throughout embryonic development, and bone homeostasis in the adults. Due to the fact that genetic variation might influence structural functions, this study is aimed to determine the pathogenic effect of nonsynonymous single-nucleotide polymorphisms (nsSNPs) in BMP genes. The implications of these variations, investigated using computational analysis and molecular models of the mature TGF-β domain, revealed the impact of modifications on the function of BMP protein. The three-dimensional (3D) structure analysis was performed on the nsSNP Y316S, V386G, E387G, C389G, and C391G nsSNP in the TGF-β domain of chicken BMP2 and H344P, S347P, V357A nsSNP in the TGF-β domain of chicken BMP4 protein that was anticipated to be harmful and of high risk. The ability of the proteins to perform variety of tasks interact with other molecules depends on their tertiary structural composition. The current analysis revealed the four most damaging variants (Y316S, V386G, E387G, C389G, and C391G), highly conserved and functional and are located in the TGF-beta domain of BMP2 and BMP4. The amino acid substitutions E387G, C389G, and C391G are discovered in the binding region. It was observed that the mutations in the TGF-beta domain caused significant changes in its structural organization including the substrate binding sites. Current findings will assist future research focused on the role of these variants in BMP function loss and their role in skeletal disorders, and this will possibly help to develop practical strategies for treating bone-related conditions.

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Section: Discussionmentioning

confidence: 99%

Computational Insights into the Structural and Functional Impacts of nsSNPs of Bone Morphogenetic Proteins

Ahmad

Ijaz

Afzal

et al. 2022

BioMed Research International

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“…The FecB (fecundity Booroola) mutation was first detected in high-fecundity Australian Booroola Merino sheep (1) 4) revealed that the effect of FecB mutation was due to the substitution of a base (A to G at 746 bp, A746G) in the BMPR1B (bone morphogenetic protein receptor 1B) coding region on ovine chromosome 6, resulting in the corresponding substitution of one amino acid (glutamine to arginine, Q249R). Through an impairment of the activity of the BMPR1B receptor kinase, FecB mutation weakened the inhibitory effect of the BMPR1B gene on steroid synthesis in granulosa cells, leading to the maturation and ovulation of ovulatory follicles at significantly small diameters and fewer granulosa cells in homozygous FecB sheep than those in non-FecB sheep (2,3,(5)(6)(7). In our previous study, litter size was significantly correlated with the FecB genotype in highprolificacy Chinese Small Tail Han sheep (8).…”

Section: Introductionmentioning

confidence: 88%

Insight Into Pituitary lncRNA and mRNA at Two Estrous Stages in Small Tail Han Sheep With Different FecB Genotypes

Chen

Guo

et al. 2022

Front. Endocrinol.

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The pituitary is a remarkably dynamic organ with roles in hormone (FSH and LH) synthesis and secretion. In animals with the FecB (fecundity Booroola) mutation, the pituitary experiences hormone fluctuations during the follicular–luteal transition, which is implicated in the expression and regulation of many genes and regulators. Long non-coding RNAs (lncRNAs) are a novel type of regulatory factors for the reproductive process. Nevertheless, the expression patterns of lncRNAs and their roles in FecB-mediated follicular development and ovulation remain obscure. Thus, we profiled the pituitary transcriptome during the follicular (F, 45 h after evacuation vaginal sponges) and luteal (L, 216 h after evacuation vaginal sponges) phases in FecB-mutant homozygous (BB) and wild-type (WW) Small Tail Han sheep. We identified 78 differentially expressed genes (DEGs) and 41 differentially expressed lncRNAs (DELs) between BB_F and BB_L, 32 DEGs and 26 DELs between BB_F and WW_F, 16 DEGs and 29 DELs between BB_L and WW_L, and 50 DEGs and 18 DELs between WW_F and WW_L. The results of real-time quantitative PCR (RT-qPCR) correlated well with the transcriptome data. In both the follicular and luteal phases, DEGs (GRID2, glutamate ionotropic receptor delta type subunit 2; ST14, ST14 transmembrane serine protease matriptase) were enriched in hormone synthesis, secretion, and action. MSTRG.47470 and MSTRG.101530 were the trans-regulated elements of ID1 (inhibitor of DNA binding 3, HLH protein) and the DEG ID3 (inhibitor of DNA binding 3, HLH protein), and EEF2 (eukaryotic translation elongation factor 2), respectively; these factors might be involved in melatonin and peptide hormone secretion. In the FecB-mediated follicular phase, MSTRG.125392 targeted seizure-related 6 homolog like (SEZ6L), and MSTRG.125394 and MSTRG.83276 targeted the DEG KCNQ3 (potassium voltage-gated channel subfamily Q member 3) in cis, while MSTRG.55861 targeted FKBP4 (FKBP prolyl isomerase 4) in trans. In the FecB-mediated luteal phase, LOC105613905, MSTRG.81536, and MSTRG.150434 modulated TGFB1, SMAD3, OXT, respectively, in trans. We postulated that the FecB mutation in pituitary tissue elevated the expression of certain genes associated with pituitary development and hormone secretion. Furthermore, this study provides new insights into how the pituitary regulates follicular development and ovulation, illustrated by the effect of the FecB mutation.

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“…The study of SMAD1 , SMAD2 and SMAD3 genes has focused on mice and has also been involved in animals such as pigs [ 19 ] and cattle [ 20 ]. These genes have also been studied as candidate genes for fertility in sheep such as the small-tailed sheep [ 21 , 22 ] in China, the Hu sheep [ 23 , 24 ] in China, and the Garole × Malpura × Malpura [ 25 , 26 ] in India. In the current study, the structures of the genes were analyzed by cloning the SMAD1 , SMAD2 and SMAD3 genes and using bioinformatics methods.…”

Section: Introductionmentioning

confidence: 99%

Expression and Polymorphisms of SMAD1, SMAD2 and SMAD3 Genes and Their Association with Litter Size in Tibetan Sheep (Ovis aries)

Sun

et al. 2022

Genes

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SMAD1, SMAD2, and SMAD3 are important transcription factors downstream of the TGF-β/SMAD signaling pathway that mediates several physiological processes. In the current study, we used cloning sequencing, RT-qPCR, bioinformatics methods and iMLDR technology to clone the coding region of Tibetan sheep genes, analyze the protein structure and detect the tissue expression characteristics of Tibetan sheep genes, and detect the polymorphisms of 433 Tibetan sheep and analyze their correlation with litter size. The results showed that the ORFs of the SMAD1, SMAD2 and SMAD3 genes were 1398 bp, 1404 bp and 1278 bp, respectively, and encoded 465, 467 and 425 amino acids, respectively. The SMAD1, SMAD2, and SMAD3 proteins were all unstable hydrophilic mixed proteins. SMAD1, SMAD2 and SMAD3 were widely expressed in Tibetan sheep tissues, and all were highly expressed in the uterus, spleen, ovary and lung tissues. Litter sizes of the genotype CC in the SMAD1 gene g.10729C>T locus were significantly higher than that of CT (p < 0.05). In the SMAD3 gene g.21447C>T locus, the genotype TT individuals showed a higher litter size than the CC and CT genotype individuals (p < 0.05). These results preliminarily demonstrated that SMAD1, SMAD2 and SMAD3 were the major candidate genes that affected litter size traits in Tibetan sheep and could be used as a molecular genetic marker for early auxiliary selection for improving reproductive traits during sheep breeding.

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Differential expression of BMP/SMAD signaling and ovarian-associated genes in the granulosa cells of FecB introgressed GMM sheep

Cited by 10 publications

References 77 publications

Computational Insights into the Structural and Functional Impacts of nsSNPs of Bone Morphogenetic Proteins

Computational Insights into the Structural and Functional Impacts of nsSNPs of Bone Morphogenetic Proteins

Insight Into Pituitary lncRNA and mRNA at Two Estrous Stages in Small Tail Han Sheep With Different FecB Genotypes

Expression and Polymorphisms of SMAD1, SMAD2 and SMAD3 Genes and Their Association with Litter Size in Tibetan Sheep (Ovis aries)

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