Effect of miRNA-99a along with TGF-?1(C/G +915) in female with secondary unexplained infertility
DOI:
https://doi.org/10.28922/qmj.2023.19.1.20-23الكلمات المفتاحية:
miRNA-99a, TGF-β1 SNP, mTOR and women with secondary unexplained infertilityالملخص
Background: Women infertility is a big health problem worldwide and the genetic disorders considered underling causes of unexplained female infertility. Objective: to find out the role of miR-99a and TGF-?1 SNP (G/C +915) in development of secondary unexplained infertility in women and prognostic of miR-99a. To achieve this goal, investigate the fold change of miR-99a and possibility to use them as biomarker. Also identification of TGF-?1(G/C +915)SNP by ARMS- PCR. Material and methods: case control study have been conducted, blood samples had been collected from population (patients 50) and (control 50) living in the north area of Thi-Qar province The samples collected during the period from November 2021 to July 2022. The genomic RNA and DNA were extracted from serum and blood respectively for molecular assay. Results: the mean of miR-99a fold change in patients group 3.70 ±1.18 versus 0.84 ±0.34 in control group and p< 0.001. TGF-?1 SNP +915(GC) genotype CC was more frequent significantly in patients group than in control group (p < 0.001) and the odds ratio was 19.06, and no significant difference in frequency rate of genotype GC between study groups p = 0.106. Genotype GG was less frequent significantly in patients group than in control group p = 0.046 and the odds ratio was 0.22. Conclusion: we can get a diagnostic and prognostic as biomarker, using the miR-99a which show high sensitivity 100%, specificity 98% and accuracy 100% in secondary unexplained infertility, also TGF? (+915 G/C) SNP as predisposing risk factor for developing of secondary unexplained infertility.
المراجع
Chiware, T. M., Vermeulen, N., Blondeel, K., Farquharson, R., Kiarie, J., Lundin, K., ... & Toskin, I. (2021). IVF and other ART in low-and middle-income countries: a systematic landscape analysis. Human Reproduction Update, 27(2), 213-228
Kothandaraman, N., Agarwal, A., Abu-Elmagd, M., & Al-Qahtani, M. H. (2016). Pathogenic landscape of idiopathic male infertility: new insight towards its regulatory networks. NPJ genomic medicine, 1(1), 1-9.?
Luddi, A., Pavone, V., Semplici, B., Governini, L., Criscuoli, M., Paccagnini, E., ... & Piomboni, P. (2020). Organoids of human endometrium: a powerful in vitro model for the endometrium-embryo cross-talk at the implantation site. Cells, 9(5), 1121.?
Shekibi, M., Heng, S., & Nie, G. (2022). MicroRNAs in the regulation of endometrial receptivity for embryo implantation. International Journal of Molecular Sciences, 23(11), 6210.?
Revel, A., Achache, H., Stevens, J., Smith, Y., & Reich, R. (2011). MicroRNAs are associated with human embryo implantation defects. Human reproduction, 26(10), 2830-2840.?
Li, Q. (2014). Transforming growth factor ? signaling in uterine development and function. Journal of animal science and biotechnology, 5(1), 1-9.?
Qiu, T., Teng, Y., Wang, Y., & Xu, L. (2016). Adoptive transfer of transforming growth factor-?1-induced CD4+ CD25+ regulatory T cells prevents immune response-mediated spontaneous abortion. Reproduction, Fertility and Development, 28(11), 1788-1797.?
Cebinelli, G. C. M., Trugilo, K. P., Garcia, S. B., & de Oliveira, K. B. (2016). TGF-?1 functional polymorphisms: a review. European cytokine network, 27, 81-89.?
Zhao, J., Chen, F., Zhou, Q., Pan, W., Wang, X., Xu, J., ... & Yang, H. (2016). Aberrant expression of microRNA-99a and its target gene mTOR associated with malignant progression and poor prognosis in patients with osteosarcoma. OncoTargets and therapy, 1589-1597.?
Pianese, L., et al. "Real time PCR quantification of frataxin mRNA in the peripheral blood leucocytes of Friedreich ataxia patients and carriers." Journal of Neurology, Neurosurgery & Psychiatry 75.7 (2004): 1061-1063.?
Grainger DJ. Heathcote K, Ciano M, et al. (1999). Genetic control of the circulating concentration of transforming growth factor type beta1. Hum Mol Genet, 8(1):39-97.
Singh M, Chaudhry P, Asselin E. Bridging. (2011). endometrial receptivity and implantation: network of hormones, cytokines, and growth factors. J Endocrinol, 210:5–14.
Maurya VK, Jha RK, Kumar V, Joshi A, Chadchan S, Mohan JJ, Laloraya M. (2013). Transforming growth factor-beta 1 (TGF-B1) liberation from its latent complex during embryo implantation and its regulation by estradiol in mouse. Biol Reprod, 89:84.
Feng G, Chenchen Si, Mingjuan Zhou, Jingwen Wang, Dan Zhang, Peter C K Leung, Bufang Xu, Aijun Zhang (2018). Decreased PECAM1-mediated TGF-?1 expression in the mid-secretory endometrium in women with recurrent implantation failure. Human Reproduction, 33(5), 832–843.
Mohammadzadeh, A., Pourfathollah, A. A., Shahrokhi, S., Hashemi, S. M., Moradi, S. L. A., and Soleimani, M. (2014). Immunomodulatory effects of adipose-derived mesenchymal stem cells on the gene expression of major transcription factors of T cell subsets. Int. Immunopharmacol, 20, 316–321.
Zhang, H., Caudle, Y., Wheeler, C., Zhou, Y., Stuart, C., Yao, B., et al. (2018). TGF-?1/Smad2/3/Foxp3 signaling is required for chronic stress-induced immune suppression. J. Neuroimmunol, 314, 30–41.
Farnaz Marhemati, Ramazan Rezaei, Anahita Mohseni Meybodi, Robabeh Taheripanah, Shayan Mostafaei & Davar Amani (2020). Transforming growth factor beta 1 (TGF?1) polymorphisms and unexplained infertility: A genetic association study. Systems Biology in Reproductive Medicine, 66:4, 267-280.
Mitra, A.; Luna, J.I.; Marusina, A.I.; Merleev, A.; Kundu-Raychaudhuri, S.; Fiorentino, D.; Raychaudhuri, S.P.; Maverakis, E. (2015). Dual MTOR Inhibition Is Required to Prevent TGF-?-Mediated Fibrosis: Implications for Scleroderma. J. Investig. Dermatol, 135, 2873–2876.
Laplante M & Sabatini DM. (2012). MTOR signaling in growth control and disease. Cell. 149. 274–293.
Chatterjee A, Mukhopadhyay S, Tung K, Patel D & Foster DA. (2015). Rapamycin-induced G1 cell cycle arrest employs both TGF-? and Rb pathways. Cancer Letters, 360 134–140.
Li N & Liu L. (2018). Mechanism of resveratrol in improving ovarian function in a rat model of premature ovarian insufficiency. Journal of Obstetrics and Gynaecology Research, 44 1431–1438.
Martin, P. M., & Sutherland, A. E. (2001). Exogenous amino acids regulate trophectoderm differentiation in the mouse blastocyst through an mTOR-dependent pathway. Developmental biology, 240(1), 182-193.?
Craciunas, L., Gallos, I., Chu, J., Bourne, T., Quenby, S., Brosens, J. J., & Coomarasamy, A. (2019). Conventional and modern markers of endometrial receptivity: a systematic review and meta-analysis. Human reproduction update, 25(2), 202-223.?
Murakami M, Ichisaka T, Maeda M, Oshiro N, Hara K, Edenhofer F, et al. (2004). mTOR is essential for growth and proliferation in early mouse embryos and embryonic stem cells. Mol. Cell Biol., 24:6710–8.
Zeng X, Mao X, Huang Z, Wang F, Wu G & Qiao S (2013). Arginine enhances embryo implantation in rats through PI3K/PKB/mTOR/NO signaling pathway during early pregnancy. Reproduction, 145 1–7.
Wang X, Li Y, Qi W, Zhang N, Sun M, Huo Q, et al. (2015). MicroRNA-99a inhibits tumor aggressive phenotypes through regulating HOXA1 in breast cancer cells. Oncotarget, 6:32737–47.
Rosario, F. J., Gupta, M. B., Myatt, L., Powell, T. L., Glenn, J. P., Cox, L., & Jansson, T. (2019). Mechanistic target of rapamycin complex 1 promotes the expression of genes encoding electron transport chain proteins and stimulates oxidative phosphorylation in primary human trophoblast cells by regulating mitochondrial biogenesis. Scientific reports, 9(1), 246.?
Correia, B., Sousa, M. I., & Ramalho-Santos, J. (2020). The mTOR pathway in reproduction: from gonadal function to developmental coordination, Reproduction, 159(4), R173-R188.
Adhikari D, Zheng W, Shen Y, Gorre N, Hamalainen T, Cooney AJ, Huhtaniemi I, Lan ZJ & Liu K. (2010) Tsc/mTORC1 signaling in oocytes governs the quiescence and activation of primordial follicles. Human Molecular Genetics, 19 397–410.
Dou X, Sun Y, Li J, Zhang J, Hao D, Liu W, Wu R, Kong F, Peng X & Li J. (2017) Short-term rapamycin treatment increases ovarian lifespan in young and middle-aged female mice. Aging Cell, 16 825–836.
