Characteristics of CACNA1C protein expression levels in the round ligaments of the uterus in patients with genital prolapse

封面

如何引用文章

全文:

开放存取 开放存取
受限制的访问 ##reader.subscriptionAccessGranted##
受限制的访问 订阅或者付费存取

详细

Genital prolapse (GP) is a multifactorial disease that is influenced by various factors such as childbirth, obstetric trauma, age, and increased intra-abdominal pressure. However, not all individuals with these factors develop GP, highlighting the importance of gene and protein expression levels for understanding the underlying cause.

Objective: This study aimed to investigate the expression of the α1C subunit of the CaV1.2 calcium channel in the round ligaments of patients with GP.

Materials and methods: This study included 61 patients, with 31 in the GP group (group I, study group) and 30 with other gynecological conditions (group II, control group). The mean age of the patients was 55.6 and 46.5 years, respectively. In group I, 12/31 (38.7%) patients had grade II–III uterine and vaginal wall prolapse, whereas 15/31 (48.38%) and 4/31 (12.9%) patients had incomplete and complete GP, respectively. The control group did not have GP. The level of α1C protein expression in the round ligaments of the uterus was examined using Western blot.

Results: Group I exhibited lower α1C protein expression (3.034 [0.8108; 4.040] RU) than group II (4.098 [2.508; 6.543] RU) (p=0.0045). Reduced α1C protein expression in group I was associated with a sarcopenic phenotype, including muscle wasting and asthenia in 9/31 (29%), myopia in 7/31 (22%), hypotension in 16/31 (51%), constipation in 17/31 (54%), phlebopathy in 11/31 (35%), pelvic floor protrusion and relaxation in 16/31 (51%), apical GP in 24/31 (77%), hypermobility in 24/31 (77%), and flat feet in 15/31 (48%) patients.

Conclusion: Patients with GP had lower α1C protein expression than those in the control group. The low expression of α1C protein is indicative of a clinical symptom complex of connective tissue dysplasia (CTD), which aligns with the concept of a "sarcopenic phenotype." In patients with CTD and a sarcopenic phenotype, the labor process is associated with low α1C protein expression levels, which contributes to the development of GP. The specific form of GP (apical) is influenced by alterations in the calcium channel function, resulting in decreased α1C protein expression.

全文:

受限制的访问

作者简介

Mikhail Cheremin

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation

编辑信件的主要联系方式.
Email: mkhrznt@gmail.com
ORCID iD: 0000-0002-8600-068X

Obstetrician-Gynecologist, PhD student

俄罗斯联邦, Moscow

Tatyana Smolnova

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation

Email: smoltat@list.ru
ORCID iD: 0000-0003-3543-651X

Dr. Med. Sci., Senior Researcher at the Department of General Surgery

俄罗斯联邦, Moscow

Alexey Krasnyi

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation

Email: a_krasnyi@oparina4.ru
ORCID iD: 0000-0001-7883-2702

PhD (Bio), Head of the Cytology Laboratory

俄罗斯联邦, Moscow

Alsu Sadekova

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation

Email: a_sadekova@oparina4.ru

Researcher at the Cytology Laboratory

俄罗斯联邦, Moscow

Vladimir Chuprynin

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation

Email: v_chuprynin@oparina4.ru
ORCID iD: 0009-0003-7856-2863

PhD, Head of the Department of Surgery

俄罗斯联邦, Moscow

参考

  1. Zamponi G.W., Striessnig J., Koschak A., Dolphin A.C. The physiology, pathology, and pharmacology of voltage-gated calcium channels and their future therapeutic potential. Pharmacol. Rev. 2015; 67(4): 821-70. https://dx.doi.org/10.1124/pr.114.009654.
  2. Смольнова Т.Ю., Красный А.М., Чупрынин В.Д., Садекова А.А.,Чурсин В.В., Тамбиева Ф.Р. Способ хирургической коррекции пролапса гениталий у пациентки со сниженным уровнем экспрессии гена CACNA1C в круглых связках матки. Акушерство и гинекология. 2020; 12: 234-41. [Smolnova T.Yu., Krasnyi A.M., Chuprynin V.D., Sadekova A.A., Chursin V.V., Tаmbieva F.R. Surgical procedure to correct genital prolapse in a patient with reduced CACNA1C gene expression in the round ligament of the uterus. Obstetrics and Gynecology. 2020; (12): 234-41. (in Russian)]. https:// dx.doi.org/10.18565/aig.2020.12.234-241.
  3. Смольнова Т.Ю., Красный А.М., Садекова А.А., Чупрынин В.Д. Роль экспрессии кальциевых каналов CAV1.2 в развитии некоторых патологических состояний в акушерстве и гинекологии. Акушерство и гинекология. 2020; 8: 5-11. [Smolnova T.Yu., Krasnyi A.M., Sadekova A.A., Chuprynin V.D. Role of CaV1.2 calcium channel expression in the development of some pathological conditions in obstetrics and gynecology. Obstetrics and Gynecology. 2020; (8): 5-11. (in Russian)]. https://dx.doi.org/10.18565/aig.2020.8.5-11.
  4. Moon A.L., Haan N., Wilkinson L.S., Thomas K.L., Hall J. CACNA1C: association with psychiatric disorders, behavior, and neurogenesis. Schizophr. Bull. 2018; 44(5): 958-65. https://dx.doi.org/10.1093/schbul/ sby096.
  5. Ehlinger D.G., Commons K.G. Cav1.2 L-type calcium channels regulate stress coping behavior via serotonin neurons. Neuropharmacology. 2019; 144: 282-90. https://dx.doi.org/10.1016/j.neuropharm.2018.08.033.
  6. Chang X., Dong Y. CACNA1C is a prognostic predictor for patients with ovarian cancer. J. Ovarian Res. 2021; 14(1): 88. https://dx.doi.org/10.1186/ s13048-021-00830-z.
  7. Смольнова Т.Ю., Красный А.М., Чупрынин В.Д., Волгина Н.Е., Никитцева О.В. Влияние уровня экспрессии а-1 субъединицы потенциал-зависимого кальциевого канала Cav1.2 в гладкомышечной ткани у пациенток с пролапсом гениталий. В сборнике: XIII Международный конгресс по репродуктивной медицине 21-24 января 2019: 126-9. [Smolnova T.Yu., Krasnyi A.M., Chuprynin V.D., Volgina N.E., Nikittseva O.V. Effect of a-1 expression level subunit of voltage-dependent calcium channel Cav1.2 in smooth muscle tissue in patients with genital prolapse. In the collection: XIII International Congress on Reproductive Medicine January 21-24, 2019: 126-9. (in Russian)].
  8. Красный А.М., Озернюк Н.Д. Экспрессия генов, кодирующих субъединицы потенциал-зависимых Са2+-каналов L-типа в пролиферирующих и дифференцирующихся миобластах линии С2С12 мыши. Известия Российской академии наук. Серия биологическая. 2011; 3: 349-53. [Krasnyi A.M., Ozernyuk N.D. The expression of genes encoding the voltage-dependent L-type Ca2+ channels in proliferating and differentiating C2C12 myoblasts of mice. Izvestiya Rossiiskoi Akademii Nauk. Seriya biologicheskaya. 2011; (3): 349-53. (in Russian)].
  9. Клинические рекомендации Российского научного медицинского общества терапевтов по диагностике, лечению и реабилитации пациентов с дисплазиями соединительной ткани (первый пересмотр). Медицинский вестник Северного Кавказа. 2018; 13(1.2): 137-209. [Guidelines of the Russian Scientific Medical Society of Internal Medicine on the diagnosis, treatment and rehabilitation of patients with the connective tissue dysplasia (first edition). Medical News of North Caucasus. 2018; 13(1.2): 137-209. (in Russian)]. https://dx.doi.org/10.14300/mnnc.2018.13037.
  10. Åkervall S., Al-Mukhtar Othman J., Molin M., Gyhagen M. Symptomatic pelvic organ prolapse in middle-aged women: a national matched cohort study on the influence of childbirth. Am. J. Obstet. Gynecol. 2020; 222(4): 356.e1- 356.e14. https://dx.doi.org/10.1016/j.ajog.2019.10.007.
  11. Deeb M.E., Awwad J., Yeretzian J.S., Kaspar H.G. Prevalence of reproductive tract infections, genital prolapse, and obesity in a rural community in Lebanon. Bull. World Health Organ. 2003; 81(9): 639-45.
  12. Marahatta R.K., Shah A. Genital prolapse in women of Bhaktapur, Nepal. Nepal Med. Coll. J. 2003; 5(1): 31-3.
  13. Gyhagen M., Al-Mukhtar Othman J., Åkervall S., Nilsson I., Milsom I. The symptom of vaginal bulging in nulliparous women aged 25-64 years: a national cohort study. Int. Urogynecol. J. 2019; 30(4): 639-47. https://dx.doi.org/10.1007/s00192-018-3684-5.
  14. Смольнова Т.Ю. Пролапс гениталий и дисплазия соединительной ткани. Клиническая и экспериментальная хирургия. Журнал им. акад. Б.В. Петровского. 2015; 2: 53-64. [Smolnova T.Yu. Women’s genital prolapse and connective tissue disease. Clin. Experiment. Surg. Petrovsky J. 2015; (2): 53-64. (in Russian)].
  15. Смольнова Т.Ю., Савельев С.В., Яковлева Н.И., Гришин В.Л., Барабанов В.М. Феномен генерализованной цитопатии у пациенток с опущением и выпадением внутренних половых органов как фенотипическое проявление синдрома дисплазии соединительной ткани на тканевом уровне. Медицинский вестник Северного Кавказа. 2008; 2: 44-9. [Smolnova T.Yu., Savelyev S.V., Yakovleva N.I., Grishin V.L., Barabanov V.M. Phenomenon of generalized cytopathia in women with prolapse and loss of internal genitals - as phenotypical sign of the connective tissue dysplasia syndrome at the tissue level. Medical News of North Caucasus. 2008; (2): 44-9. (in Russian)].
  16. Смольнова Т.Ю., Адамян Л.В. Динамика фенотипических признаков синдрома дисплазии соединительной ткани в различные возрастные периоды. Актуальность проблемы в акушерстве и гинекологии. Акушерство и гинекология. 2013; 4: 74-9. [Smolnova T.Yu., Adamyan L.V. Time course of changes in the phenotypic signs of connective tissue dysplasia at different ages: the urgency of the problem in obstetrics and gynecology. Obstetrics and Gynecology. 2013; (4): 74-9. (in Russian)].
  17. Жабченко И.А., Олешко В.Ф. Особенности течения беременности и родов, состояние плода и новорожденного у женщин с нарушениями обтурационной функции шейки матки при гестации. Охрана материнства и детства. 2016; 1(27): 5-9. [Zhabchenko I.A., Oleshko V.F. Peculiarities of pregnancy course and delivery, fetus and newborn condition in women with obstructive failure of cervix function. Maternal and child welfare. 2016; 1(27): 5-9. (in Russian)].
  18. Нечаева Г.И., Яковлев В.М., Конев В.П., Друк И.В., Морозов С.Л. Дисплазия соединительной ткани: основные клинические синдромы, формулировка диагноза, лечение. Лечащий врач. 2008; 2: 22-5. [Nechaeva G.I., Yakovlev V.M., Konev V.P., Druk I.V., Morozov S.L. Connective tissue dysplasia: the main clinical syndromes, diagnosis, treatment. Lechashchiy vrach. 2008; 2: 22-5. (in Russian)].
  19. Фотина Е.В., Закирова Р.Р., Алексеенкова М.В., Панина О.Б. Дисплазия соединительной ткани в генезе истмико-цервикальной недостаточности. Акушерство, гинекология и репродукция. 2021; 15(1): 41-50. [Fotina E.V., Zakirova R.R., Alekseenkova M.V., Panina O.B. Connective tissue dysplasia in the genesis of cervical incompetence. Obstetrics, Gynecology and Reproduction. 2021; 15(1): 41-50. (in Russian)]. https://dx.doi.org/10.17749/2313-7347/ob.gyn.rep.2020.131.
  20. Alcalay M., Stav K., Eisenberg V.H. Family history associated with pelvic organ prolapse in young women. Int. Urogynecol. J. 2015; 26(12): 1773-6. https://dx.doi.org/10.1007/s00192-015-2779-5.
  21. Samimi P., Jones S.H., Giri A. Family history and pelvic organ prolapse: a systematic review and meta-analysis. Int. Urogynecol. J. 2021; 32(4): 759-74. https://dx.doi.org/10.1007/s00192-020-04559-z.
  22. Richter H.E., Sridhar A.., Nager C.W., Komesu Y.M., Harvie H.S., Zyczynski H.M. et al.; Eunice Kennedy Shriver National Institute of Child Health and Human Development Pelvic Floor Disorders Network. Characteristics associated with composite surgical failure over 5 years of women in a randomized trial of sacrospinous hysteropexy with graft vs vaginal hysterectomy with uterosacral ligament suspension. Am. J. Obstet. Gynecol. 2023; 228(1): 63.e1-63.e16. https://dx.doi.org/10.1016/ j.ajog.2022.07.048.
  23. Смольнова Т.Ю., Адамян Л.В. Клинико-патогенетические аспекты опущения и выпадения внутренних половых органов при недифференцированных формах дисплазии соединительной ткани. Кубанский научный медицинский вестник. 2009; 6(111): 69-73. [Smol’nova T.J., Adamyan L.V. Clinico-pathogenetic respectives of genital prolapse in patients with nondifferencial connective tissue disease. Kuban Scientific Medical Bulletin. 2009; 6(111): 69-73. (in Russian)].
  24. Смольнова Т.Ю., Адамян Л.В., Сидоров В.В. Состояние микроциркуляторного русла у больных с пролапсом гениталий. В кн.: Кулаков В.И., Адамян Л.В., ред. Современные технологии в диагностике и лечении гинекологических заболеваний. М.: ПАНТОРИ; 2006: 170-2. [Smolnova T.Yu., Adamyan L.V., Sidorov V.V. State of the microvasculature in patients with genital prolapse. In: Kulakov V.I., Adamyan L.V., ed. Modern technologies in the diagnosis and treatment of gynecological diseases. M.: PANTORI; 2006: 170-2. (in Russian)].
  25. Смольнова Т.Ю. Особенности гемодинамики и ее связь с некоторыми клиническими проявлениями у женщин при дисплазии соединительной ткани. Клиническая медицина. 2013; 10: 43-8. [Smol’nova T.Yu. Features hemodynamics and its relationship with some clinical manifestations in women with connective tissue dysplasia. Clinical Medicine. 2013; (10): 43-8. (in Russian)].
  26. Смольнова Т.Ю., Адамян Л.В., Сидоров В.В. Особенности микроциркуляции при опущении и выпадении внутренних половых органов у женщин репродуктивного возраста. Акушерство и гинекология. 2007; 1: 39-44. [Smolnova T.Yu., Adamyan L.V., Sidorov V.V. Microcirculatory features in descent and prolapse of the internal genitals in reproductive-aged females. Obstetrics and Gynecology. 2007; (1): 39-44. (in Russian)].

补充文件

附件文件
动作
1. JATS XML
2. Fig. 1. Analysis of extragenital pathology of female patients

下载 (379KB)
3. Fig. 2. Comparative analysis of α1C protein expression (Western blot)

下载 (78KB)
4. Fig. 3. α1C content in the tissue of the round ligament of the uterus (Western blot)

下载 (189KB)

版权所有 © Bionika Media, 2024
##common.cookie##