ometendoОжирение и метаболизмObesity and metabolism2071-87132306-5524Endocrinology Research Centre10.14341/omet13018ometendo-13018Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL STUDIESВлияние метформиновой терапии и обработки аллостерическим агонистом лютеинизирующего гормона и хорионическим гонадотропином на сперматогенез у самцов крыс с ожирениемInfluence of metformin therapy and treatment with an allosteric luteinizing hormone agonist and chorionic gonadotropin on spermatogenesis in male rats with obesityhttps://orcid.org/0000-0001-6555-9540ДеркачК. В.DerkachK. V.

Деркач Кира Викторовна, к.б.н.

Researcher ID: AAN-1060-2020Scopus Author ID: 6603743572eLibrary SPIN: 6925-1558

194223, Санкт-Петербург, проспект Тореза, д. 44

Kira V. Derkach, PhD in biology

Researcher ID: AAN-1060-2020Scopus Author ID: 6603743572eLibrary SPIN: 6925-1558

44 Thorez Avenue, 194223 Saint-Petersburg

derkatch_k@list.ruhttps://orcid.org/0000-0002-2252-0088МоринаИ. Ю.MorinaI. Yu.

Морина Ирина Юрьевна, к.б.н.

eLibrary SPIN: 3489-8842

Санкт-Петербург

Irina Yu. Morina, PhD in biology

eLibrary SPIN: 3489-8842

St. Petersburg

irinamorina@mail.ruhttps://orcid.org/0000-0001-5543-8657БаюноваЛ. В.BayunovaL. V.

Баюнова Любовь Владимировна, к.б.н.

eLibrary SPIN: 2833-2978

Санкт-Петербург

Lyubov V. Bayunova, PhD in biology

eLibrary SPIN: 2833-2978

St. Petersburg

bayunoval@mail.comhttps://orcid.org/0000-0002-2060-2020БахтюковА. А.BakhtuykovA. A.

Бахтюков Андрей Андреевич, к.б.н.

eLibrary SPIN: 7073-0586

Санкт-Петербург

Andrey A. Bakhtyukov, PhD in biology

eLibrary SPIN: 7073-0586

St. Petersburg

bahtyukov@gmail.comhttps://orcid.org/0009-0000-5217-0624ДиденкоЕ. А.DidenkoE. A.

Диденко Егор Александрович

Санкт-Петербург

Egor A. Didenko

St. Petersburg

didenkoegor58@mail.ruhttps://orcid.org/0000-0002-4917-2175СорокоумовВ. Н.SorokoumovV. N.

Сорокоумов Виктор Николаевич, к.х.н.

eLibrary SPIN: 1042-8142

Санкт-Петербург

Viktor N. Sorokoumov, PhD in chemistry

eLibrary SPIN: 1042-8142

St. Petersburg

sorokoumov@gmail.comhttps://orcid.org/0000-0002-0348-0631РомановаИ. В.RomanovaI. V.

Романова Ирина Владимировна, д.б.н.

eLibrary SPIN: 8891-8186

Санкт-Петербург

Irina V. Romanova, PhD in biology

eLibrary SPIN: 8891-8186

St. Petersburg

irinaromanova@mail.ruhttps://orcid.org/0000-0002-4293-3162ШпаковА. О.ShpakovA. O.

Шпаков Александр Олегович, д.б.н., профессор

eLibrary SPIN: 6335-8311

Санкт-Петербург

Alexander O. Shpakov, PhD in biology, Professor

eLibrary SPIN: 6335-8311

St. Petersburg

alex_shpakov@list.ruИнститут эволюционной физиологии и биохимии им. И.М. Сеченова Российской академии наукРоссияI.M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of SciencesRussian FederationИнститут эволюционной физиологии и биохимии им. И.М. Сеченова Российской академии наук; Институт химии Санкт-Петербургского государственного университетаРоссияI.M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences; Institute of Chemistry, St. Petersburg State UniversityRussian Federation202316082023203217226Copyright © Деркач К.В., Морина И.Ю., Баюнова Л.В., Бахтюков А.А., Диденко Е.А., Сорокоумов В.Н., Романова И.В., Шпаков А.О., 20232023Деркач К.В., Морина И.Ю., Баюнова Л.В., Бахтюков А.А., Диденко Е.А., Сорокоумов В.Н., Романова И.В., Шпаков А.О.Derkach K.V., Morina I.Y., Bayunova L.V., Bakhtuykov A.A., Didenko E.A., Sorokoumov V.N., Romanova I.V., Shpakov A.O.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.omet-endojournals.ru/jour/article/view/13018Обоснование

Обоснование. У мужчин ожирение сопровождается комплексом метаболических и гормональных расстройств, что приводит к андрогенному дефициту и нарушению сперматогенеза. Для коррекции репродуктивных дисфункций могут быть использованы антидиабетические препараты, включая метформин (МФ), и агонисты рецептора лютеинизирующего гормона (ЛГР), активирующие тестикулярный стероидогенез. Однако при диета-индуцированном ожирении (ДИО) эффективность и механизмы их действия мало изучены.

Цель

Цель. Оценить восстанавливающий эффект МФ, хорионического гонадотропина человека (ХГЧ) и аллостерического ЛГР-агониста ТП03, различающихся по природе и механизмам действия, на уровни тестостерона, сперматогенез и морфологию семенных канальцев у самцов крыс с ДИО.

Материалы и методы

Материалы и методы. Ожирение у самцов крыс Wistar вызывали 23-недельной диетой, обогащенной насыщенными жирами. Обработку МФ проводили в течение 5 нед в дозе 120 мг/кг/сут (перорально), обработку ХГЧ и ТП03 — в течение 5 сут в суточных дозах 20 МЕ/крысу (п/к) и 15 мг/кг (в/б) соответственно. С помощью микроскопии и гистохимического анализа оценивали число и подвижность сперматозоидов (СП), число их дефектных форм и морфологию семенных канальцев, с помощью иммуноферментного анализа — уровни тестостерона и других гормонов в крови.

Результаты

Результаты. МФ, ХГЧ и ТП03 в различной степени повышали сниженные у ДИО-крыс количество СП и долю их подвижных форм, в том числе с поступательным движением, нормализовали толщину эпителия семенных канальцев и количество в них сперматогониев и пахитеновых сперматоцитов, но не снижали повышенную при ДИО долю дефектных СП. В случае МФ это было ассоциировано с вызываемыми этим препаратом нормализацией массы тела, толерантности к глюкозе, уровней инсулина и лептина у ДИО-крыс. Положительное влияние ХГЧ и ТП03 на сперматогенез было обусловлено их стимулирующим эффектом на продукцию тестостерона.

Заключение

Заключение. Применение длительной МФ-терапии и краткосрочных курсов ЛГР-агонистов нормализует нарушенный при ДИО сперматогенез, что указывает на перспективы их использования для улучшения мужской фертильности при ожирении, причем в случае МФ ключевое значение имеет нормализация метаболического и гормонального статуса, а в случае ЛГР-агонистов — их стероидогенный эффект.

BACKGROUND

BACKGROUND: In men, obesity is accompanied by a complex of metabolic and hormonal disorders, which leads to androgen deficiency and impaired spermatogenesis. Antidiabetic drugs, including metformin (MF), and luteinizing hormone receptor (LHR) agonists, which activate testicular steroidogenesis, can be used to correct reproductive dysfunctions. However, in diet-induced obesity (DIO), their effectiveness and mechanisms of action are poorly understood.

AIM

AIM: In men, obesity is accompanied by a complex of metabolic and hormonal disorders, which leads to androgen deficiency and impaired spermatogenesis. Antidiabetic drugs, including metformin (MF), and luteinizing hormone receptor (LHR) agonists, which activate testicular steroidogenesis, can be used to correct reproductive dysfunctions. However, in dietinduced obesity (DIO), their effectiveness and mechanisms of action are poorly understood.

MATERIALS AND METHODS

MATERIALS AND METHODS: Obesity in male Wistar rats was induced by a 23-week diet enriched with saturated fats. MF treatment was carried out for 5 weeks at a dose of 120 mg/kg/day (orally), and the treatment with hCG and TP03 was carried out for 5 days at daily doses of 20 IU/rat (s.c.) and 15 mg/kg (i.p.), respectively. Using microscopy and histochemical analysis, the number and motility of spermatozoa (SP), the number of their defective forms and the morphology of the seminiferous tubules were assessed, and the levels of testosterone and other hormones in the blood were measured using ELISA.

RESULTS

RESULTS: MF, hCG, and TP03 to varying degrees increased the number of SP and the proportion of their mobile forms, including those with forward movement, which were reduced in DIO rats, and also normalized the thickness of the epithelium of the seminiferous tubules and the number of spermatogonia and pachytene spermatocytes in them, but did not reduced the proportion of defective forms of SP, increased in DIO. In the case of MF, this was associated with the drug-induced normalization of body weight, glucose tolerance, and the insulin and leptin levels in DIO rats. The positive effect of hCG and TP03 on spermatogenesis was due to their stimulating effect on testosterone production.

CONCLUSION

CONCLUSION: The use of long-term MF therapy and short-term courses of LHR-agonists normalizes impaired spermatogenesis in DIO, which indicates the prospects for their use to improve male fertility in obesity, and in the case of MF therapy, normalization of the metabolic and hormonal status is of great importance, while in the case of LHR-agonists the most important factor is their steroidogenic effect.

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