Association Of the BMP4 Genes Polymorphism with Physiological Traits

Authors

  • Boraq Jaafar Abdullah
  • Sajad alkhanjer
  • Ali R. Abid

Keywords:

Bone morphogenetic proteins (BMPs), cumulus cells (CCs), cattle, granulosa and theca cells

Abstract


 Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-β family of proteins that have been implicated in the paracrine regulation of granulosa cell (GC) function  , The growth and development of follicles within the ovary are highly dependent on autocrine and paracrine signaling involving growth factors from granulosa cells, theca cells, stromal interstitial cells, and the oocytes, The growth factor bone morphogenetic protein-4 (BMP-4) and its receptor (BMPR-IB) have been detected in ovaries,  The objective of the current study was designed to Association of the BMP4 genes polymorphism with physiological traits in Iraqi cattle. So far, more than 30 members have been identified in the BMP family of which BMP4 is the most important one. BMP4 can inhibit progesterone production by granulosa cells and decrease basal granulosa cells progesterone secretion and totally abolish FSH-stimulating action both in cattle and sheep. BMP-4 promotes primordial follicle development and the primordial-to-primary follicle transition, BMP-4 plays an important role in promoting the survival and development of primordial follicles in the neonatal ovary. The expression and function of bone morphogenetic protein 4 (BMP4) gene in bovine cumulus cells (CCs) was investigated to reveal the mechanisms by which it regulated cell apoptosis and proliferation. BMPs are intra-ovarian factors expressed in mammalian ovaries by oocytes, granulosa and theca cells.

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References

Ajafar, M. H., Kadhim, A. H., Al-Thuwaini, T. M., Al-Shuhaib, M. B. S., & Hussein, T. H. (2023). Association of bone morphogenetic protein 15 and growth differentiation factor 9 with litter size in livestock: a review study. Acta Scientiarum. Animal Sciences, 45, e5792

Akira Nifuji, Odile Kellermann, Yoshinori Kuboki, John M. Wozney, Masaki Noda, (1997). Perturbation of BMP Signaling in Somitogenesis Resulted in Vertebral and Rib Malformations in the Axial Skeletal Formation, Journal of Bone and Mineral Research, Volume 12, Issue 3, 1 March 1997, Pages 332–342, https://doi.org/10.1359/jbmr.1997.12.3.332

aloza, S., Abo-Salem, M., Hemeda, S. (2017). Effect of Genetic Variations in BMP 4 Gene (Exon 2 Plus Part of Intron 2) on Infertility in Egyptian Buffalo Cows. Benha Journal of Applied Sciences, 2(2), 37-41. doi: 10.21608/bjas.2017.167116

Andrews, M. G., Del Castillo, L. M., Ochoa-Bolton, E., Yamauchi, K., Smogorzewski, J., & Butler, S. J. (2017). BMPs direct sensory interneuron identity in the developing spinal cord using signal-specific not morphogenic activities. eLife, 6, e30647. https://doi.org/10.7554/eLife.30647

Avasthi, K. K., Agarwal, A., & Agarwal, S. (2022). Association of MTHFR, BMP4, TGFA and IRF6 Polymorphisms with Non-Syndromic Cleft lip and Palate in North Indian Patients. Avicenna journal of medical biotechnology, 14(2), 175–180. https://doi.org/10.18502/ajmb.v14i2.8879

Baloza, S., Abo-Salem, M., Hemeda, S. (2017). Effect of Genetic Variations in BMP 4 Gene (Exon 2 Plus Part of Intron 2) on Infertility in Egyptian Buffalo Cows. Benha Journal of Applied Sciences, 2(2), 37-41. doi: 10.21608/bjas.2017.167116

Bleuming SA, He XC, Kodach LL, Hardwick JC, Koopman FA, Ten Kate FJ, van Deventer SJ, Hommes DW, Peppelenbosch MP, Offerhaus GJ, Li L, van den Brink GR (Sep 2007). "Bone morphogenetic protein signaling suppresses tumorigenesis at gastric epithelial transition zones in mice". Cancer Research. 67 (17): 8149–55. doi: 10.1158/0008-5472.CAN-06-4659. PMID 17804727.

Bragdon, B., Moseychuk, O., Saldanha, S., King, D., Julian, J., & Nohe, A. (2011). Bone morphogenetic proteins: a critical review. Cellular signalling, 23(4), 609-620.‏

Celestino, J. J., Lima-Verde, I. B., Bruno, J. B., Matos, M. H., Chaves, R. N., Saraiva, M. V., Silva, C. M., Faustino, L. R., Rossetto, R., Lopes, C. A., Donato, M. A., Peixoto, C. A., Campello, C. C., Silva, J. R., & Figueiredo, J. R. (2011). Steady-state level of bone morphogenetic protein-15 in goat ovaries and its influence on in vitro development and survival of preantral follicles. Molecular and cellular endocrinology, 338(1-2), 1–9. https://doi.org/10.1016/j.mce.2011.02.007

Chalazonitis, A., D'Autréaux, F., Guha, U., Pham, T. D., Faure, C., Chen, J. J., Roman, D., Kan, L., Rothman, T. P., Kessler, J. A., & Gershon, M. D. (2004). Bone morphogenetic protein-2 and -4 limit the number of enteric neurons but promote development of a TrkC-expressing neurotrophin-3-dependent subset. The Journal of neuroscience: the official journal of the Society for Neuroscience, 24(17), 4266–4282. https://doi.org/10.1523/JNEUROSCI.3688-03.2004

Chalazonitis, A., Pham, T. D., Li, Z., Roman, D., Guha, U., Gomes, W., Kan, L., Kessler, J. A., & Gershon, M. D. (2008). Bone morphogenetic protein regulation of enteric neuronal phenotypic diversity: relationship to timing of cell cycle exit. The Journal of comparative neurology, 509(5), 474–492. https://doi.org/10.1002/cne.21770

Chang, H. M., Qiao, J., & Leung, P. C. (2016). Oocyte-somatic cell interactions in the human ovary-novel role of bone morphogenetic proteins and growth differentiation factors. Human reproduction update, 23(1), 1–18. https://doi.org/10.1093/humupd/dmw039.

Charlene L. McCord, Mark W. Westneat. (2016). Phylogenetic relationships and the evolution of BMP4 in triggerfishes and filefishes (Balistoidea). Volume 94, Part A, January 2016, Pages 397-409. https://doi.org/10.1016/j.ympev.2015.09.014

Chen, D., Zhao, M., & Mundy, G. R. (2004). Bone Morphogenetic Proteins. Growth Factors, 22(4), 233–241.https://doi.org/10.1080/08977190412331279890

Cheng, H., Gao, X., Huard, M., Lu, A., Ruzbarsky, J. J., Amra, S., Wang, B., & Huard, J. (2022). Bone morphogenetic protein 4 rescues the bone regenerative potential of old muscle-derived stem cells via regulation of cell cycle inhibitors. Stem cell research & therapy, 13(1), 385. https://doi.org/10.1186/s13287-022-03047-z.

Chu, Y. L., Xu, Y. R., Yang, W. X., & Sun, Y. (2018). The role of FSH and TGF-β superfamily in follicle atresia. Aging (Albany NY), 10(3), 305.‏

Díaz, P. U., Hein, G. J., Belotti, E. M., Rodríguez, F. M., Rey, F., Amweg, A. N., Matiller, V., Baravalle, M. E., Ortega, H. H., & Salvetti, N. R. (2016). BMP2, 4 and 6 and BMPR1B are altered from early stages of bovine cystic ovarian disease development. Reproduction (Cambridge, England), 152(4), 333–350. https://doi.org/10.1530/REP-15-0315

Eric E. Nilsson, Michael K. Skinner, (2003). Bone Morphogenetic Protein-4 Acts as an Ovarian Follicle Survival Factor and Promotes Primordial Follicle Development, Biology of Reproduction, Volume 69, Issue 4, 1 October 2003, Pages 1265–1272, https://doi.org/10.1095/biolreprod.103.018671

Faure, C., Chalazonitis, A., Rhéaume, C., Bouchard, G., Sampathkumar, S. G., Yarema, K. J., & Gershon, M. D. (2007). Gangliogenesis in the enteric nervous system: roles of the polysialylation of the neural cell adhesion molecule and its regulation by bone morphogenetic protein 4. Developmental dynamics: an official publication of the American Association of Anatomists, 236(1), 44–59. https://doi.org/10.1002/dvdy.20943

Fu, M., Vohra, B. P., Wind, D., & Heuckeroth, R. O. (2006). BMP signaling regulates murine enteric nervous system precursor migration, neurite fasciculation, and patterning via altered Ncam1 polysialic acid addition. Developmental biology, 299(1), 137–150. https://doi.org/10.1016/j.ydbio.2006.07.016

Ganjoo, S., Puebla-Osorio, N., Nanez, S., Hsu, E., Voss, T., Barsoumian, H., ... & Cortez, M. A. (2022). Bone morphogenetic proteins, activins, and growth and differentiation factors in tumor immunology and immunotherapy resistance. Frontiers in immunology, 13, 1033642.‏

Glister, C., Satchell, L., & Knight, P. G. (2011). Granulosal and thecal expression of bone morphogenetic protein- and activin-binding protein mRNA transcripts during bovine follicle development and factors modulating their expression in vitro. Reproduction (Cambridge, England), 142(4), 581–591. https://doi.org/10.1530/REP-11-0150

Guan, R., Yuan, L., Li, J., Wang, J., Li, Z., Cai, Z., Guo, H., Fang, Y., Lin, R., Liu, W., Wang, L., Zheng, Q., Xu, J., Zhou, Y., Qian, J., Ding, M., Luo, J., Li, Y., Yang, K., Sun, D., … Lu, W. (2022). Bone morphogenetic protein 4 inhibits pulmonary fibrosis by modulating cellular senescence and mitophagy in lung fibroblasts. The European respiratory journal, 60(6), 2102307. https://doi.org/10.1183/13993003.02307-2021

Haas, C. S., Rovani, M. T., Ilha, G. F., Bertolin, K., Ferst, J. G., Bridi, A., ... & Gasperin, B. G. (2019). Transforming growth factor-beta family members are regulated during induced luteolysis in cattle. Animal Reproduction, 16, 829-837.‏

Huang, F., Hu, L., Zhang, Y., Qu, X., & Xu, J. (2021). BMP4 Moderates Glycolysis and Regulates Activation and Interferon-Gamma Production in CD4+ T Cells. Frontiers in immunology, 12, 702211. https://doi.org/10.3389/fimmu.2021.702211

Juengel, J. L., & McNatty, K. P. (2005). The role of proteins of the transforming growth factor-beta superfamily in the intraovarian regulation of follicular development. Human reproduction update, 11(2), 143–160. https://doi.org/10.1093/humupd/dmh061

Juengel, J. L., Reader, K. L., Bibby, A. H., Lun, S., Ross, I., Haydon, L. J., & McNatty, K. P. (2006). The role of bone morphogenetic proteins 2, 4, 6 and 7 during ovarian follicular development in sheep: contrast to rat. Reproduction (Cambridge, England), 131(3), 501–513. https://doi.org/10.1530/rep.1.00958

Khare, V., Joshi, S., Thakur, M. S., Singh, A. P., & Vandre, R. (2022). Evaluation of Bone Morphogenetic Protein-4 gene polymorphism for growth traits in Indian goat breeds. The Indian Journal of Animal Sciences, 92(9), 1077-1080.‏

Kovács, T., Halasy, V., Pethő, C., Szőcs, E., Soós, Á., Dóra, D., de Santa Barbara, P., Faure, S., Stavely, R., Goldstein, A. M., & Nagy, N. (2023). Essential Role of BMP4 Signaling in the Avian Ceca in Colorectal Enteric Nervous System Development. International journal of molecular sciences, 24(21), 15664. https://doi.org/10.3390/ijms242115664

L Sarma, N Nahardeka, G Zaman, An Aziz, A Das, F Akhtar, S Upadhyay and L Borkolita. (2019). Analysis of BMP4 gene HaeIII polymorphism in Assam Hill goat. JEZS 2019; 7(2): 34-37

Lochab, A. K., & Extavour, C. G. (2017). Bone Morphogenetic Protein (BMP) signaling in animal reproductive system development and function. Developmental biology, 427(2), 258-269.‏

Mazinani, M., & Rude, B. (2020). Population, world production and quality of sheep and goat products. American Journal of Animal and Veterinary Sciences, 15(4), 291-299.‏

Namwanje, M., & Brown, C. W. (2016). Activins and Inhibins: Roles in Development, Physiology, and Disease. Cold Spring Harbor perspectives in biology, 8(7), a021881. https://doi.org/10.1101/cshperspect.a021881

Nasri, A., Foisset, F., Ahmed, E., Lahmar, Z., Vachier, I., Jorgensen, C., Assou, S., Bourdin, A., & De Vos, J. (2021). Roles of Mesenchymal Cells in the Lung: From Lung Development to Chronic Obstructive Pulmonary Disease. Cells, 10(12), 3467. https://doi.org/10.3390/cells10123467

Parrott JA, Vigne JL, Chu BZ, Skinner MK. (1994). Mesenchymal-epithelial interactions in the ovarian follicle involve keratinocyte and hepatocyte growth factor production by thecal cells and their action on granulosa cells. Endocrinology 1994; 135:569–575.

Reddi AH, Reddi A (2009). "Bone morphogenetic proteins (BMPs): from morphogens to metabologens". Cytokine & Growth Factor Reviews. 20 (5–6): 341–2. doi: 10.1016/j.cytogfr.2009.10.015. PMID 19900831.

Rossi, R. O. D. S., Portela, A. M. L. R., Passos, J. R. S., Cunha, E. V., Silva, A. W. B., Costa, J. J. N., ... & Silva, J. R. V. (2018). Effects of BMP-4 and FSH on growth, morphology and mRNA expression of oocyte-secreted factors in cultured bovine secondary follicles. Animal Reproduction (AR), 12(4), 910-919.‏

S.H. Baloza1, M.E.S. Abo-Salem2 and S.A. Hemeda. (2017). Effect of Genetic Variations in BMP 4 Gene (Exon 2 Plus Part of Intron 2) on Infertility in Egyptian Buffalo Cows. Sciences Vol. (2) Issue (2) Nov. (2017), 37- 41

Sanfins, A., Rodrigues, P., & Albertini, D. F. (2018). GDF-9 and BMP-15 direct the follicle symphony. Journal of assisted reproduction and genetics, 35(10), 1741-1750.‏

Spicer, L. J., Schutz, L. F., & Aad, P. Y. (2021). Effects of bone morphogenetic protein 4, gremlin, and connective tissue growth factor on estradiol and progesterone production by bovine granulosa cells. Journal of animal science, 99(11), skab318. https://doi.org/10.1093/jas/skab318

Szilágyi, S.S., Amsalem-Zafran, A.R., Shapira, K.E. et al. (2022). Competition between type I activin and BMP receptors for binding to ACVR2A regulates signaling to distinct Smad pathways. BMC Biol 20, 50 https://doi.org/10.1186/s12915-022-01252-z

Tian, Y. Q., Li, X. L., Wang, W. J., Hao, H. S., Zou, H. Y., Pang, Y. W., Zhao, X. M., Zhu, H. B., & Du, W. H. (2022). Knockdown of bone morphogenetic protein 4 gene induces apoptosis and inhibits proliferation of bovine cumulus cells. Theriogenology,188,28–36. https://doi.org/10.1016/j.theriogenology.2022.05.015

VAISHALI KHARE1*, SHRIKANT JOSHI1, MOHAN SINGH THAKUR1, AJIT PRATAP SINGH1 and RAJESH. (2022). Evaluation of Bone Morphogenetic Protein-4 gene polymorphism for growth traits in Indian goat breeds VANDRE1.Sciences 92 (9): 1077–1080

van Houten, E. L., Laven, J. S., Louwers, Y. V., McLuskey, A., Themmen, A. P., & Visser, J. A. (2013). Bone morphogenetic proteins and the polycystic ovary syndrome. Journal of ovarian research, 6(1), 32. https://doi.org/10.1186/1757-2215-6-32

Wang, H., Misztal, I., Aguilar, I., Legarra, A., Fernando, R. L., Vitezica, Z., ... & Muir, W. M. (2014). Genome-wide association mapping including phenotypes from relatives without genotypes in a single-step (ssGWAS) for 6-week body weight in broiler chickens. Frontiers in genetics, 5, 134.

Wang, Z., Yuan, L., Zuo, X., Racey, P. A., & Zhang, S. (2009). Variations in the sequences of BMP2 imply different mechanisms for the evolution of morphological diversity in vertebrates. Comparative biochemistry and physiology. Part D, Genomics & proteomics, 4(2), 100–104. https://doi.org/10.1016/j.cbd.2008.12.002

Wei, C., Chen, X., Peng, J., Yu, S., Chang, P., Jin, K., & Geng, Z. (2023). BMP4/SMAD8 signaling pathway regulated granular cell proliferation to promote follicle development in Wanxi white goose. Poultry science, 102(1), 102282. https://doi.org/10.1016/j.psj.2022.102282

Yamashita, H., Murayama, C., Takasugi, R., Miyamoto, A., & Shimizu, T. (2011). BMP-4 suppresses progesterone production by inhibiting histone H3 acetylation of StAR in bovine granulosa cells in vitro. Molecular and cellular biochemistry, 348(1-2), 183–190. https://doi.org/10.1007/s11010-010-0653-9

Zakin, L., & De Robertis, E. M. (2010). Extracellular regulation of BMP signaling. Current biology: CB, 20(3), R89–R92. https://doi.org/10.1016/j.cub.2009.11.021

Zhang, D. J., Wu, J. H., Husile, G., Sun, H. L., & Zhang, W. G. (2014). Sequence variation and molecular evolution of BMP4 genes. Genetics and molecular research: GMR, 13(4), 9196–9201. https://doi.org/10.4238/2014.November.7.6

Wagner, D. O., Sieber, C., Bhushan, R., Börgermann, J. H., Graf, D., & Knaus, P. (2010). BMPs: from bone to body morphogenetic proteins. Science signaling, 3(107), mr1. https://doi.org/10.1126/scisignal.3107mr1

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2025-05-05

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Abdullah BJ, alkhanjer S, Abid AR. Association Of the BMP4 Genes Polymorphism with Physiological Traits. J Neonatal Surg [Internet]. 2025May5 [cited 2025Oct.2];14(20S):509-17. Available from: https://www.jneonatalsurg.com/index.php/jns/article/view/5088

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Vol. 14 No. 20S (2025): Journal of Neonatal Surgery

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