Introduction

akusherstvo

Obstetrics, Gynecology and Reproduction

Акушерство, Гинекология и Репродукция

2313-73472500-3194

IRBIS LLC

10.17749/2313-7347/ob.gyn.rep.2023.398

akusherstvo-1826

Research Article

ОRIGINAL ARTICLES

ОРИГИНАЛЬНЫЕ СТАТЬИ

Identification of key miRNAs as regulatory biomarkers of gonadotropins leading to infertility in males

Идентификация ключевых микроРНК как регуляторных биомаркеров гонадотропинов, приводящих к мужскому бесплодию

Охайед

Н. А.

Oohayyed

N. A.

Нур А. Охайед – ассистент кафедры медицинской биотехнологии Колледжа биотехнологии

Багдад 64074

Noor A. Oohayyed – Assistant Lecturer, Department of Medical Biotechnology, College of Biotechnology

https://orcid.org/0000-0003-4455-8674

Мохаммед

М. М.

Mohammed

M. M.

Маис М. Мохаммед – ассистент

Scopus Author ID: 57561562000

Багдад 64074

Mais M. Mohammed – Assistant Lecturer

Scopus Author ID: 57561562000

https://orcid.org/0000-0002-7120-7960

Аль-Рахим

А. М.

Al-Rahim

A. M.

Ая М. Аль-Рахим – ассистент кафедры медицинской биотехнологии Колледжа биотехнологии

Scopus Author ID: 57226461520

Researcher ID: ACZ-6702-2022

Багдад 64074

Aya M. Al-Rahim – Assistant Lecturer, Department of Medical Biotechnology, College of Biotechnology

Scopus Author ID: 57226461520

Researcher ID: ACZ-6702-2022

https://orcid.org/0000-0002-1570-2537

Аль Чалаби

Р. Н.

Al Chalabi

R. N.

Раваа Н. Аль Чалаби – доктор наук, доцент кафедры медицинской биотехнологии Колледжа биотехнологии

Scopus Author ID: 57210340073

Researcher ID: ABD-7380-2020

Багдад 64074

Rawaa N. Al Chalabi – Assistant Professor, Dr, Department of Medical Biotechnology, College of Biotechnology

Scopus Author ID: 57210340073

Researcher ID: ABD-7380-2020

https://orcid.org/0000-0002-0538-8716

Шабан

С. А.

Shaban

S. A.

Семаа А. Шабан – доктор наук, доцент кафедры биологии Колледжа наук

Scopus Author ID: 57223083825

Researcher ID: H-1150-2019

Тикрит, Саладин 34001

Semaa A. Shaban – PhD, Assistant Professor, Department of Biology, College of Sciences

Scopus Author ID: 57223083825

Researcher ID: H-1150-2019

https://orcid.org/0000-0001-7427-4483

Сулейман

А. А. Дж.

Suleiman

A. A. J.

Ахмед А. Дж. Сулейман – доктор наук (биотехнология и молекулярная биология), профессор кафедры биотехнологии Колледжа наук

Scopus Author ID: 57200943508

Researcher ID: AAF-7727-2019

Эр-Рамади, Анбар 46006

Ahmed A. J. Suleiman – PhD in Biotechnology and Molecular Biology, Professor, Department of Biotechnology, College of Science

Scopus Author ID: 57200943508

Researcher ID: AAF-7727-2019

ahmed.suleiman@uoanbar.edu.iq

Университет Аль-НахрейнИракAl-Nahrain UniversityIraq

Университет медицинских и фармацевтических наук Ибн СиныИракIbn Sina University for Medical and Pharmaceutical SciencesIraq

Университет ТикритаРоссияTikrit UniversityRussian Federation

Анбарский университетИракUniversity of AnbarIraq

2023

12112023

175607624

2023

Охайед Н., Мохаммед М., Аль-Рахим А., Аль Чалаби Р., Шабан С.А., Сулейман А.

Oohayyed N., Mohammed M., Al-Rahim A., Al Chalabi R., Shaban S., Suleiman A.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://www.gynecology.su/jour/article/view/1826

Introduction

Introduction. Infertility is a highly fatal reproductive system disorder that affects the ability of a couple to reproduce. Over the past decades, a drastic uplift has been recorded in infertility cases among males ranging from 20 to 70 % indicating spermatogenesis impairment.

Aim

Aim: to identify key microRNAs (miRNAs) as regulatory biomarkers of gonadotropins involved in dysregulation of fertility-related genes to propose potential therapeutic strategies that would combat the action of oncogenic miRNAs (oncomiRs).

Materials and Methods

Materials and Methods. Interaction analysis was performed between miRNAs and fertility-related genes namely luteinizing hormone choriogonadotropin receptor (LHCGR), gonadotropin-releasing hormone receptor (GnRHR), follicle-stimulating hormone receptor (FSHR) and cystic fibrosis transmembrane conductance regulator (CFTR) to identify key miRNAs as regulatory biomarkers of gonadotropins leading to infertility in males.

Results

Results. A total of 10, 13, 31 and 18 strong and potential binding sites were predicted for miRNAs-LHCGR, miRNAs-GnRHR, miRNAs-FSHR, and miRNAs-CFTR respectively employing miRWalk (comprehensive genetic database including miRNA targets) followed by identification of 6, 18, 55 and 17 significant interactions through RNA22. Subsequently shortlisted miRNAs and messenger RNA (mRNA) regions were subjected to Vfold-Pipeline and RNAComposer individually for 3D structure prediction. Additionally molecular docking was carried out between miRNAs and mRNAs models that discovered potential and stable interactions elucidating miR-6880-FSHR(R2) as a highly stable complex with least binding affinity (-566.3) and high confidence score (0.999).

Conclusion

Conclusion. Hence this study proposes key oncomiRs as a diagnostic biomarker and therapeutic target to bring about a promising treatment strategy against male factor infertility. However wet lab investigations are required for further validations of proposed study.

Введение

Введение. Бесплодие – это крайне фатальное заболевание репродуктивной системы, которое определяет неспособность пары к воспроизведению потомства. За последние десятилетия зафиксирован резкий рост случаев бесплодия среди мужчин, составляющий от 20 до 70 %, что свидетельствует о нарушении сперматогенеза.

Цель

Цель: идентифицировать ключевые микроРНК в качестве регуляторных биомаркеров гонадотропинов, участвующих в нарушении регуляции генов, связанных с фертильностью, для определения потенциальных терапевтических стратегий по противодействию онкогенным микроРНК.

Материалы и методы

Материалы и методы. Проведен анализ взаимодействия между микроРНК и генами, связанными с фертильностью, такими как ген рецептора лютеинизирующего гормона/хориогонадотропина (англ. luteinizing hormone choriogonadotropin receptor, LHCGR), рецептора гонадотропин-рилизинг-гормона (англ. gonadotropin-releasing hormone receptor, GnRHR), рецептора фолликулостимулирующего гормона (англ. follicle-stimulating hormone receptor, FSHR) и регулятора трансмембранной проводимости при муковисцидозе (англ. cystic fibrosis transmembrane conductance regulator, CFTR), для идентификации ключевых микроРНК как регуляторных биомаркеров гонадотропинов, приводящие к мужскому бесплодию.

Результаты

Результаты. Применение базы данных miRWalk (полная генетическая база данных, включающая в себя мишени для микроРНК) позволило предсказать в общей сложности 10, 13, 31 и 18 сильных и потенциальных сайтов связывания в парах микроРНК-LHCGR, микроРНК-GnRHR, микроРНК-FSHR и микроРНК-CFTR соответственно с последующим выявлением 6, 18, 55 и 17 значимых взаимодействий посредством алгоритма РНК22. Впоследствии включенные в окончательный список микроРНК и области матричной РНК (мРНК) были попарно проанализированы с использованием программ Vfold-Pipeline и RNAComposer для прогнозирования трехмерной структуры. Кроме того, был проведен молекулярный докинганализ между моделями микроРНК и мРНК, которые показали потенциальные и стабильные взаимодействия, и выявлен высокостабильный комплекс miR-6880-FSHR(R2) с наименьшей аффинностью связывания (-566,3) и высоким показателем достоверности (0,999).

Заключение

Заключение. В настоящем исследовании предложены ключевые онкомикроРНК («oncomiRs») в качестве диагностического биомаркера и терапевтической мишени для разработки многообещающей стратегии лечения мужского бесплодия. Однако для дальнейшей проверки результатов данной работы необходимо проведение практических лабораторных исследований.

гонадотропиназооспермиябиомаркер бесплодиярецептор лютеинизирующего гормона/хориогонадотропинаLHCGRрецептор гонадотропин-рилизинг-гормонаGnRHRрецептор фолликулостимулирующего гормонаFSHR

gonadotropinazoospermiainfertility biomarkerluteinizing hormone choriogonadotropin receptorLHCGRgonadotropin-releasing hormone receptorGnRHRfollicle-stimulating hormone receptorFSHR

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The authors declare that there are no conflicts of interest present.