<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE root>
<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="review-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Kazan medical journal</journal-id><journal-title-group><journal-title xml:lang="en">Kazan medical journal</journal-title><trans-title-group xml:lang="ru"><trans-title>Казанский медицинский журнал</trans-title></trans-title-group></journal-title-group><issn publication-format="print">0368-4814</issn><issn publication-format="electronic">2587-9359</issn><publisher><publisher-name xml:lang="en">Eco-Vector</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">635674</article-id><article-id pub-id-type="doi">10.17816/KMJ635674</article-id><article-id pub-id-type="edn">YXEJCE</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>Reviews</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>Обзоры</subject></subj-group><subj-group subj-group-type="article-type"><subject>Review Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Non-Coding Nucleic Acid Sequences and Female Infertility</article-title><trans-title-group xml:lang="ru"><trans-title>Роль некодирующих последовательностей нуклеиновых кислот в развитии женского бесплодия</trans-title></trans-title-group><trans-title-group xml:lang="zh"><trans-title>核酸的非编码序列在女性不育发展中的作用</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0001-5841-0606</contrib-id><name-alternatives><name xml:lang="en"><surname>Morozovsky</surname><given-names>Maxim A.</given-names></name><name xml:lang="ru"><surname>Морозовский</surname><given-names>Максим Александрович</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>4 year student, Faculty of Medicine and Biology</p></bio><bio xml:lang="ru"><p>студент IV курса, медико-биологический факультет</p></bio><email>morozovskiy0m@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-5269-736X</contrib-id><contrib-id contrib-id-type="spin">1336-8363</contrib-id><name-alternatives><name xml:lang="en"><surname>Spirina</surname><given-names>Liudmila V.</given-names></name><name xml:lang="ru"><surname>Спирина</surname><given-names>Людмила Викторовна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, Dr. Sci. (Medicine), Assistant Professor, Depart. of Biochemistry and Molecular Biology with a course in Clinical Laboratory Diagnostics, Leading research associate, Lab. of Tumor Biochemistry</p></bio><bio xml:lang="ru"><p>доктор медицинских наук, доцент, заведующий, каф. биохимии и молекулярной биологии с курсом клинической лабораторной диагностики, ведущий научный сотрудник, лаб. биохимии опухолей</p></bio><email>spirinalvl@mail.ru</email><xref ref-type="aff" rid="aff1"/><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7082-9389</contrib-id><name-alternatives><name xml:lang="en"><surname>Merkulov</surname><given-names>Evgeny D.</given-names></name><name xml:lang="ru"><surname>Меркулов</surname><given-names>Евгений Дмитриевич</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>4 year student, Faculty of Medicine and Biology</p></bio><bio xml:lang="ru"><p>студент IV курса, медико-биологический факультет</p></bio><email>evmerc@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Siberian State Medical University</institution></aff><aff><institution xml:lang="ru">Сибирский государственный медицинский университет</institution></aff></aff-alternatives><aff-alternatives id="aff2"><aff><institution xml:lang="en">Cancer Research Institute — Tomsk National Research Medical Center</institution></aff><aff><institution xml:lang="ru">Научно-исследовательский институт онкологии — Томский национальный исследовательский медицинский центр</institution></aff></aff-alternatives><pub-date date-type="preprint" iso-8601-date="2025-05-30" publication-format="electronic"><day>30</day><month>05</month><year>2025</year></pub-date><pub-date date-type="pub" iso-8601-date="2025-06-15" publication-format="electronic"><day>15</day><month>06</month><year>2025</year></pub-date><volume>106</volume><issue>3</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>414</fpage><lpage>421</lpage><history><date date-type="received" iso-8601-date="2024-09-15"><day>15</day><month>09</month><year>2024</year></date><date date-type="accepted" iso-8601-date="2025-01-10"><day>10</day><month>01</month><year>2025</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2025, Eco-Vector</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2025, Эко-Вектор</copyright-statement><copyright-statement xml:lang="zh">Copyright ©; 2025,</copyright-statement><copyright-year>2025</copyright-year><copyright-holder xml:lang="en">Eco-Vector</copyright-holder><copyright-holder xml:lang="ru">Эко-Вектор</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/" start_date="2028-06-15"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by-nc-sa/4.0</ali:license_ref></license></permissions><self-uri xlink:href="https://kazanmedjournal.ru/kazanmedj/article/view/635674">https://kazanmedjournal.ru/kazanmedj/article/view/635674</self-uri><abstract xml:lang="en"><p>Female infertility is one of the least investigated forms of reproductive dysfunction. This review presents promising molecular factors associated with infertility and analyzes the mechanisms involved in its manifestation and progression. Globally, up to 17.5% of couples experience infertility, which can negatively affect individual health and society as a whole. Female-related factors account for approximately 37% of cases. The presence of numerous factors associated with chronic inflammatory diseases of the reproductive system, including genetic and environmental influences, pose significant challenges for treatment of this patient population. Epigenetic mechanisms represent promising targets for regulation. MicroRNAs (miRNAs) are short non-coding RNA sequences that are approximately 18–25 nucleotides long. They regulate a wide range of various physiological processes within the cell, including cell growth, signal transduction, apoptosis, and pathological processes. Several miRNAs, including miR-324, miR-155, miR-335-5p, miR-9119, miR-23a, miR-27a, and miR-146b-5p, may be associated with female infertility. The role of long non-coding sequences influencing the activity of key targets involved in granulosa cell maturation is also highlighted. These factors have been shown to act as regulatory RNAs and mediate the decidualization of stromal cells. Particular attention is given to circulating miRNAs such as let-7b, miR-29a, miR-30a, miR-140, and miR-320a.</p></abstract><trans-abstract xml:lang="ru"><p>Женское бесплодие относится к одной из наименее изученных форм репродуктивной патологии. В обзоре представлены перспективные молекулярные факторы, связанные с развитием бесплодия, проанализированы механизмы, участвующие в манифестации и прогрессировании данной патологии. До 17,5% пар в мире сталкиваются с проблемами бесплодия, что может негативно сказаться на здоровье самих пар и общества в целом. Женские факторы — причина примерно 37% случаев бесплодия. Наличие большого количества факторов, ассоциированных с развитием хронических воспалительных заболеваний репродуктивной системы, в т. ч. генетических, а также факторов внешней среды, является существенной сложностью в лечении данной категории пациентов. Эпигенетические механизмы представляют собой перспективные мишени для регуляции. МикроРНК — короткие последовательности некодирующей РНК примерно от 18 до 25 нуклеотидов. Они также оказывают глубокое воздействие на различные физиологические процессы внутри клетки, включая клеточный рост, передачу сигналов, апоптоз и патологические процессы. miR-324, miR-155, miR-335-5p, miR-9119, miR-23a<bold>,</bold><bold> </bold>miR-27a и miR-146b-5p могут быть ассоциированы с развитием женского бесплодия. Обозначена роль длинных некодирующих последовательностей, влияющих на активность ключевых мишеней, определяющих созревание гранулёзных клеток. Показано, что данные факторы способны выступать в качестве регуляторной РНК и опосредовать децидуализацию стромальных клеток. Выявлено, что особое значение придаётся циркулирующим микроРНК let-7b, miR-29a, miR-30a, miR-140, miR-320a.</p></trans-abstract><trans-abstract xml:lang="zh"><p>女性不孕症是研究最少的生殖病理学形式之一。 该综述提出了与不孕症发展相关的有希望的分子因素，分析了这种病理表现和进展所涉及的机制。 世界上高达17.5％的夫妇面临不孕症问题，这会对夫妇本身和整个社会的健康产生负面影响。 女性因素是大约37％不孕症病例的原因。 与生殖系统慢性炎症性疾病发展相关的大量因素的存在，包括 遗传和环境因素是治疗这一类患者的一个重大挑战。 表观遗传机制代表了有希望的调节目标。 microRNAs是约18至25个核苷酸的非编码RNA的短序列。 它们对细胞内的各种生理过程也有深远的影响，包括细胞生长，信号传导，细胞凋亡和病理过程。 miR-324、miR-155、miR-335-5p、miR-9119、miR-23a、miR-27a和miR-146b-5p可能与女性不育的发展有关。 指出了长非编码序列影响决定肉芽细胞成熟的关键靶标的活性的作用。 已经表明，这些因子可以充当调节RNA并介导基质细胞的凋亡。 发现特别重视循环microRNAs let-7b、miR-29a、miR-30a、miR-140、miR-320a。</p></trans-abstract><kwd-group xml:lang="en"><kwd>non-coding nucleic acid sequences</kwd><kwd>female infertility</kwd><kwd>microRNA</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>некодирующие последовательности нуклеиновых кислот</kwd><kwd>женское бесплодие</kwd><kwd>микроРНК</kwd></kwd-group><kwd-group xml:lang="zh"><kwd>核酸的非编码序列</kwd><kwd>雌性不育</kwd><kwd>microRNA</kwd></kwd-group><funding-group/></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Męczekalski B, Niwczyk O, Battipaglia C, et al. Neuroendocrine disturbances in women with functional hypothalamic amenorrhea: an update and future directions. Endocrine. 2023;84(3):769–785. doi: 10.1007/s12020-023-03619-w EDN: XLBEHI</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Mihalas BP, Redgrove KA, McLaughlin EA, Nixon B. Molecular mechanisms responsible for increased vulnerability of the ageing oocyte to oxidative damage. Oxid Med Cell Longev. 2017;2017:4015874. doi: 10.1155/2017/4015874</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Gordon CM, Ackerman KE, Berga SL, et al. Functional hypothalamic amenorrhea: an endocrine society clinical practice guideline. J Clin Endocrinol Metabol. 2017;102(5):1413–1439. doi: 10.1210/jc.2017-00131 EDN: SVDBOH</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Canipari R, De Santis L, Cecconi S. Female fertility and environmental pollution. IJERPH. 2020;17(23):8802. doi: 10.3390/ijerph17238802 EDN: RDOMJG</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>Vitagliano A, Petre GC, Francini-Pesenti F, et al. Dietary supplements for female infertility: a critical review of their composition. Nutrients. 2021;13(10):3552. doi: 10.3390/nu13103552 EDN: VZBVHW</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>Łakoma K, Kukharuk O, Śliż D. the influence of metabolic factors and diet on fertility. Nutrients. 2023;15(5):1180. doi: 10.3390/nu15051180 EDN: PPPGUO</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Silvestris E, Lovero D, Palmirotta R. Nutrition and female fertility: an interdependent correlation. Front Endocrinol. 2019;10:346. doi: 10.3389/fendo.2019.00346 EDN: LZOGAB</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Panth N, Gavarkovs A, Tamez M, Mattei J. The influence of diet on fertility and the implications for public health nutrition in the United States. Front Public Health. 2018;6:211. doi: 10.3389/fpubh.2018.00211</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Simionescu G, Doroftei B, Maftei R, et al. The complex relationship between infertility and psychological distress (Review). Exp Ther Med. 2021;21(4):306. doi: 10.3892/etm.2021.9737 EDN: TRWKUA</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Skoracka K, Ratajczak AE, Rychter AM, et al. female fertility and the nutritional approach: the most essential aspects. Adv Nutr. 2021;12(6):2372–2386. doi: 10.1093/advances/nmab068 EDN: BQCFOD</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>Munro MG, Balen AH, Cho S, et al; FIGO Committee on menstrual disorders and related health impacts, and FIGO committee on reproductive medicine, endocrinology, and infertility. The FIGO ovulatory disorders classification system†. Hum Reprod. 2022;37(10):2446–2464. doi: 10.1093/humrep/deac180.;PMCID EDN: BPEQCK</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Sasaki H, Hamatani T, Kamijo S, et al. Impact of oxidative stress on age-associated decline in oocyte developmental competence. Front Endocrinol. 2019;10:811. doi: 10.3389/fendo.2019.00811</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>Ding X, Schimenti JC. Female infertility from oocyte maturation arrest: assembling the genetic puzzle. EMBO Mol Med. 2023;15(6):e17729. doi: 10.15252/emmm.202317729 EDN: RRRYTY</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>Wang W, Guo J, Shi J, et al. Bi-allelic pathogenic variants in PABPC1L cause oocyte maturation arrest and female infertility. EMBO Mol Med. 2023;15(6):e17177. doi: 10.15252/emmm.202217177 EDN: RWDJKO</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>Feng R, Sang Q, Kuang Y, et al. Mutations in TUBB8 and human oocyte meiotic arrest. N Engl J Med. 2016;374(3):223–232. doi: 10.1056/NEJMoa1510791</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>Feng R, Yan Z, Li B, et al. Mutations in TUBB8 cause a multiplicity of phenotypes in human oocytes and early embryos. J Med Genet. 2016;53(10):662–671. doi: 10.1136/jmedgenet-2016-103891</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>Chen B, Zhang Z, Sun X, et al. Biallelic mutations in PATL2 cause female infertility characterized by oocyte maturation arrest. Am J Hum Genet. 2017;101(4):609–615. doi: 10.1016/j.ajhg.2017.08.018</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>Dougherty MP, Poch AM, Chorich LP, et al. Unexplained female infertility associated with genetic disease variants. N Engl J Med. 2023;388(11):1055–1056. doi: 10.1056/NEJMc2211539 EDN: FSBJSH</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>Huang HL, Lv C, Zhao YC, et al. Mutant ZP1 in familial infertility. N Engl J Med. 2014;370(13):1220–1226. doi: 10.1056/NEJMoa1308851</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>Liu W, Li K, Bai D, et al. Dosage effects of ZP2 and ZP3 heterozygous mutations cause human infertility. Hum Genet. 2017;136(8):975–985. doi: 10.1007/s00439-017-1822-7 EDN: DFYPZF</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>Fontana L, Garzia E, Marfia G, et al. Epigenetics of functional hypothalamic amenorrhea. Front Endocrinol. 2022;13:953431. doi: 10.3389/fendo.2022.953431 EDN: BKBEVO</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>Geng X, Zhao J, Huang J, et al. lnc-MAP3K13-7:1 Inhibits Ovarian GC Proliferation in PCOS via DNMT1 Downregulation-mediated CDKN1A promoter hypomethylation. Mol Ther. 2021;29(3):1279–1293. doi: 10.1016/j.ymthe.2020.11.018 EDN: JTBOTQ</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>Bahmyari S, Jamali Z, Khatami SH, et al. MICRORNAS in female infertility: an overview. Cell Biochem Funct. 2021;39(8):955–969. doi: 10.1002/cbf.3671 EDN: SRRPYC</mixed-citation></ref><ref id="B24"><label>24.</label><mixed-citation>Guo Y, Sun J, Lai D. Role of microRNAs in premature ovarian insufficiency. Reprod Biol Endocrinol. 2017;15(1):38. doi: 10.1186/s12958-017-0256-3 EDN: ZQDWQN</mixed-citation></ref><ref id="B25"><label>25.</label><mixed-citation>Yuanyuan Z, Zeqin W, Xiaojie S, et al. proliferation of ovarian granulosa cells in polycystic ovarian syndrome is regulated by MicroRNA-24 by targeting wingless-type family member 2B (WNT2B). Med Sci Monit. 2019;25:4553–4559. doi: 10.12659/MSM.915320 EDN: DXAWRG</mixed-citation></ref><ref id="B26"><label>26.</label><mixed-citation>Xia H, Zhao Y. miR-155 is high-expressed in polycystic ovarian syndrome and promotes cell proliferation and migration through targeting PDCD4 in KGN cells. Artif Cells Nanomed Biotechnol. 2020;48(1):197–205. doi: 10.1080/21691401.2019.1699826</mixed-citation></ref><ref id="B27"><label>27.</label><mixed-citation>Wang L, Chen Y, Wu S, et al. miR-135a Suppresses granulosa cell growth by targeting Tgfbr1 and Ccnd2 during folliculogenesis in mice. Cells. 2021;10(8):2104. doi: 10.3390/cells10082104 EDN: WFRBWD</mixed-citation></ref><ref id="B28"><label>28.</label><mixed-citation>Yao L, Li M, Hu J, et al. MiRNA-335-5p negatively regulates granulosa cell proliferation via SGK3 in PCOS. Reproduction. 2018;156(5):439–449. doi: 10.1530/REP-18-0229</mixed-citation></ref><ref id="B29"><label>29.</label><mixed-citation>Ding Y, He P, Li Z. MicroRNA-9119 regulates cell viability of granulosa cells in polycystic ovarian syndrome via mediating Dicer expression. Mol Cell Biochem. 2020;465(1–2):187–197. doi: 10.1007/s11010-019-03678-6 EDN: MPFXUM</mixed-citation></ref><ref id="B30"><label>30.</label><mixed-citation>Nie M, Yu S, Peng S, et al. miR-23a and miR-27a promote human granulosa cell apoptosis by targeting SMAD51. Biol Reproduct. 2015;93(4). doi: 10.1095/biolreprod.115.130690</mixed-citation></ref><ref id="B31"><label>31.</label><mixed-citation>Dong L, Xin X, Chang HM, et al. Expression of long noncoding RNAs in the ovarian granulosa cells of women with diminished ovarian reserve using high-throughput sequencing. J Ovarian Res. 2022;15(1):119. doi: 10.1186/s13048-022-01053-6 EDN: DFHTBN</mixed-citation></ref><ref id="B32"><label>32.</label><mixed-citation>Xiang Z, Lv Q, Chen X, et al. Lnc GNG12-AS1 knockdown suppresses glioma progression through the AKT/GSK-3β/β-catenin pathway. Biosci Rep. 2020;40(8):BSR20201578. doi: 10.1042/BSR20201578</mixed-citation></ref><ref id="B33"><label>33.</label><mixed-citation>Aljubran F, Nothnick WB. Long non-coding RNAs in endometrial physiology and pathophysiology. Mol Cell Endocrinol. 2021;525:111190. doi: 10.1016/j.mce.2021.111190 EDN: GVVWEV</mixed-citation></ref><ref id="B34"><label>34.</label><mixed-citation>Takamura M, Zhou W, Rombauts L, Dimitriadis E. The long noncoding RNA PTENP1 regulates human endometrial epithelial adhesive capacity in vitro: implications in infertility. Biol Reproduct. 2020;102(1):53–62. doi: 10.1093/biolre/ioz173</mixed-citation></ref><ref id="B35"><label>35.</label><mixed-citation>Scalici E, Traver S, Mullet T, et al. Circulating microRNAs in follicular fluid, powerful tools to explore in vitro fertilization process. Sci Rep. 2016;6(1):24976. doi: 10.1038/srep24976</mixed-citation></ref><ref id="B36"><label>36.</label><mixed-citation>Galimov ShN, Galimova EF, Gilyazova IR, et al. Expression of exosomal microRNAs miR-34a and miR-210 in male infertility: relationship with morphokinetic parameters and sperm DNA fragmentation. Urology Herald. 2024;12(4):34–42. doi: 10.21886/2308-6424-2024-12-4-34-42 EDN: FAFNXQ</mixed-citation></ref></ref-list></back></article>
