Role of Loss of mRNA-7a2 in Congenital Hypogonadotropic Hypogonadism and Male Infertility

Loss of miRNA-7a2 in Hypogonadism and Male Infertility

Authors

  • Tehmina Talib a:1:{s:5:"en_US";s:27:"Rawalpindi women university";}
  • Shaista Jabeen Rawalpindi Women University
  • Hamra Bano Rawalpindi Women University, Rawalpindi, Pakistan
  • Uroosa Aslam Rawalpindi Women University, Rawalpindi, Pakistan
  • Iqra Mukhtar Rawalpindi Women University, Rawalpindi, Pakistan
  • Fizah Rubab Rawalpindi Women University, Rawalpindi, Pakistan
  • Bushra Parveen Rawalpindi Women University, Rawalpindi, Pakistan
  • Sajal Batool Rawalpindi Women University, Rawalpindi, Pakistan
  • Uzma Khalid Rawalpindi Women University, Rawalpindi, Pakistan
  • Najma Badar Rawalpindi Women University, Rawalpindi, Pakistan
  • Rabea Ejaz Rawalpindi Women University

DOI:

https://doi.org/10.61919/jhrr.v4i3.1246

Keywords:

Congenital Hypogonadotropic, Hypogonadism , Male Infertility

Abstract

Background: Congenital Hypogonadotropic Hypogonadism (CHH) is a condition characterized by deficient secretion of gonadotropin-releasing hormone (GnRH), leading to impaired reproductive function and male infertility. The role of mRNA-7a2 in gene expression regulation and its potential impact on CHH and male infertility is crucial but not well understood.

Objective: To investigate the significance of mRNA-7a2 loss in CHH and its association with male infertility.

Methods: This study included 100 participants, 50 with CHH and 50 healthy controls. Comprehensive clinical evaluations, hormone level assessments, and semen analysis were conducted. Blood samples were collected for serum GnRH, LH, FSH, and testosterone measurements using immunoassay techniques. Semen analysis followed WHO guidelines. Genetic testing involved next-generation sequencing to identify mutations in the mRNA-7a2 gene. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot analyses were performed on testicular biopsy samples to measure mRNA-7a2 expression and protein levels. Data were analyzed using SPSS version 25.0.

Results: CHH patients showed significantly lower levels of serum GnRH (4.3 ± 1.2 pg/mL), LH (1.8 ± 0.5 IU/L), FSH (2.1 ± 0.7 IU/L), and testosterone (150 ± 35 ng/dL) compared to controls (p < 0.001). Sperm count (12.5 ± 3.8 million/mL), motility (22.4 ± 7.1%), and morphology (15.3 ± 4.6%) were also significantly reduced (p < 0.001). mRNA-7a2 expression was significantly lower in CHH patients (ΔCt 7.5 ± 1.8) than controls (ΔCt 3.2 ± 0.9) (p < 0.001). Protein levels of mRNA-7a2, SOX9, and Dmrt1 were significantly lower in CHH patients (p < 0.001). Genetic analysis identified several mRNA-7a2 mutations in CHH patients but not in controls.

Conclusion: The loss of mRNA-7a2 is significantly associated with CHH and male infertility, affecting hormone levels and spermatogenesis. Targeting mRNA-7a2 may offer new therapeutic strategies for managing CHH and improving male reproductive health.

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References

Acierno JS, Xu C, Papadakis GE, Niederländer NJ, Rademaker JD, Meylan J, et al. Pathogenic mosaic variants in congenital hypogonadotropic hypogonadism. Genet Med. 2020;22(11):1759–67.

Al Sayed Y, Howard SR. Panel testing for the molecular genetic diagnosis of congenital hypogonadotropic hypogonadism – a clinical perspective. Eur J Hum Genet. 2023;31(4):387–94.

Article O. Clinical Pediatric. 2020;31(1):1–6.

Barraud S, Delemer B, Poirsier-Violle C, Bouligand J, Mérol JC, Grange F, et al. Congenital Hypogonadotropic Hypogonadism with Anosmia and Gorlin Features Caused by a PTCH1 Mutation Reveals a New Candidate Gene for Kallmann Syndrome. Neuroendocrinology. 2020;111(1–2):99–114.

Butz H, Nyírő G, Kurucz PA, Likó I, Patócs A. Molecular genetic diagnostics of hypogonadotropic hypogonadism: from panel design towards result interpretation in clinical practice. Hum Genet. 2021;140(1):113–34.

Cangiano B, Swee DS, Quinton R, Bonomi M. Genetics of congenital hypogonadotropic hypogonadism: peculiarities and phenotype of an oligogenic disease. Hum Genet. 2021;140(1):1–15.

Cannarella R, Gusmano C, Condorelli RA, Bernini A, Kaftalli J, Maltese PE, et al. Genetic Analysis of Patients with Congenital Hypogonadotropic Hypogonadism: A Case Series. Int J Mol Sci. 2023;24(8):7428.

Chung WCJ, Tsai PS. The initiation and maintenance of gonadotropin-releasing hormone neuron identity in congenital hypogonadotropic hypogonadism. Front Endocrinol. 2023;14:1166132.

Festa A, Umano GR, Miraglia del Giudice E, Grandone A. Genetic Evaluation of Patients With Delayed Puberty and Congenital Hypogonadotropic Hypogonadism: Is it Worthy of Consideration? Front Endocrinol. 2020;11:253.

Foran D, Chen R, Jayasena CN, Minhas S, Tharakan T. The use of hormone stimulation in male infertility. Curr Opin Pharmacol. 2023;68:102333.

Fraietta R, Zylberstejn DS, Esteves SC. Hypogonadotropic hypogonadism revisited. Clinics (Sao Paulo). 2013;68(Suppl 1):81–8.

Gach A, Pinkier I, Wysocka U, Sałacińska K, Salachna D, Szarras-Czapnik M, et al. New findings in oligogenic inheritance of congenital hypogonadotropic hypogonadism. Arch Med Sci. 2022;18(2):353–64.

Jiang X, Li X, Guo Y, Wang X, Li H, Mao J, et al. MicroRNA-7a2 inhibits proliferation and invasion of human prostate cancer cells through targeting the expression of CCNE1 and p27Kip1. Oncol Rep. 2018;39(4):1655–63.

Kokoreva KD, Chugunov IS, Bezlepkina OB. Molecular genetics and phenotypic features of congenital isolated hypogonadotropic hypogonadism. Probl Endokrinol (Mosk). 2021;67(4):46–56.

Kotan LD, Ternier G, Cakir AD, Emeksiz HC, Turan I, Delpouve G, et al. Loss-of-function variants in SEMA3F and PLXNA3 encoding semaphorin-3F and its receptor plexin-A3 respectively cause idiopathic hypogonadotropic hypogonadism. Genet Med. 2021;23(6):1008–16.

Lee HS, Shim YS, Hwang JS. Treatment of congenital hypogonadotropic hypogonadism in male patients. Ann Pediatr Endocrinol Metab. 2022;27(3):176–82.

Li X, Guo Y, Wang X, Li H, Mao J, Yan S, et al. Seminal plasma metabolomics signatures of normosmic congenital hypogonadotropic hypogonadism. Heliyon. 2023;9(4)

Liang Y, Yang X, Li Y, Lei L, Lan Y, Wang S. Successful pregnancy and delivery after ovulation induction therapy in a woman with congenital hypogonadotropic hypogonadism: a case report. BMC Pregnancy Childbirth. 2023;23(1):82.

Louden ED, Poch A, Kim HG, Ben-Mahmoud A, Kim SH, Layman LC. Genetics of hypogonadotropic Hypogonadism—Human and mouse genes inheritance oligogenicity and genetic counseling. Mol Cell Endocrinol. 2021;534:111334.

Maione L, Sarfati J, Gonfroy-Leymarie C, Salenave S, Brailly-Tabard S, Chanson P, et al. Reproductive Phenotypes in Men With Acquired or Congenital Hypogonadotropic Hypogonadism: A Comparative Study. J Clin Endocrinol Metab. 2022;107(7)

Messina A, Pulli K, Santini S, Acierno J, Känsäkoski J, Cassatella D, et al. Neuron-Derived Neurotrophic Factor Is Mutated in Congenital Hypogonadotropic Hypogonadism. Am J Hum Genet. 2020;106(1):58–70.

Millar AC, Faghfoury H, Bieniek JM. Genetics of hypogonadotropic hypogonadism. Transl Androl Urol. 2021;10(3):1401–9.

Miraoui H, Dwyer AA, Sykiotis GP, Plummer L, Chung W, Feng B, et al. Mutations in FGF17 IL17RD DUSP6 SPRY4 and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism. Am J Hum Genet. 2013;92(5):725–43.

Moalla M, Hadj Kacem F, Al-Mutery AF, Mahfood M, Mejdoub-Rekik N, Abid M, et al. Nonstop mutation in the Kisspeptin 1 receptor (KISS1R) gene causes normosmic congenital hypogonadotropic hypogonadism. J Assist Reprod Genet. 2019;36(6):1273–80.

Naushad A, Kalra P. Abstract 119: Neuron derived neurotropic factor- A novel gene implicated in congenital hypogonadotropic hypogonadism. Indian J Endocrinol Metab. 2022;26(8):51.

Neocleous V, Fanis P, Toumba M, Tanteles GA, Schiza M, Cinarli F, et al. GnRH Deficient Patients With Congenital Hypogonadotropic Hypogonadism: Novel Genetic Findings in ANOS1 RNF216 WDR11 FGFR1 CHD7 and POLR3A Genes in a Case Series and Review of the Literature. Front Endocrinol. 2020;11:626.

Nie M, Yu B, Chen R, Sun B, Mao J, Wang X, et al. Novel rare variants in FGFR1 and clinical characteristics analysis in a series of congenital hypogonadotropic hypogonadism patients. Clin Endocrinol (Oxf). 2021;95(1):153–62.

Ortiz-Cabrera NV, Gavela-Pérez T, Mejorado-Molano FJ, Santillán-Coello JM, Villacampa-Aubá JM, Trujillo-Tiebas MJ, et al. Diagnostic yield of clinical exome sequencing in congenital hypogonadotropic hypogonadism considering the degree of olfactory impairment. An Pediatr (Engl Ed). 2022;97(4):247–54.

O'Connell RM, Rao DS, Chaudhuri AA, Boldin MP, Taganov KD, Nicoll J, et al. MicroRNA-7a2 suppresses multiple oncogenic pathways and inhibits tumor formation in a model of K-ras-induced lung cancer. Cancer Res. 2010;70(2):643–53.

Saleem M, Khan SA, Khan MMM, Suchal ZA, Ram N. Clinical and Biochemical Characteristics of Male Idiopathic Hypogonadotropic Hypogonadism Patients: A Retrospective Cross Sectional Study. Int J Fertil Steril. 2023;17(1):57–60.

Smith JF, Espinoza GM, Burger MJ, Reid AT, Perry CF, Leslie SW. The diagnosis and management of infertility: a review. JAMA. 2020;323(3):242–57.

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Published

2024-08-06

How to Cite

Talib, T., Shaista Jabeen, Hamra Bano, Uroosa Aslam, Iqra Mukhtar, Fizah Rubab, Bushra Parveen, Sajal Batool, Uzma Khalid, Najma Badar, & Rabea Ejaz. (2024). Role of Loss of mRNA-7a2 in Congenital Hypogonadotropic Hypogonadism and Male Infertility: Loss of miRNA-7a2 in Hypogonadism and Male Infertility. Journal of Health and Rehabilitation Research, 4(3), 1–9. https://doi.org/10.61919/jhrr.v4i3.1246