Influence of metformin therapy and treatment with an allosteric luteinizing hormone agonist and chorionic gonadotropin on spermatogenesis in male rats with obesity

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...

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Main Authors: K. V. Derkach, I. Yu. Morina, L. V. Bayunova, A. A. Bakhtuykov, E. A. Didenko, V. N. Sorokoumov, I. V. Romanova, A. O. Shpakov
Format: Article
Language:English
Published: Endocrinology Research Centre 2023-11-01
Series:Ожирение и метаболизм
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Online Access:https://www.omet-endojournals.ru/jour/article/view/13018
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author K. V. Derkach
I. Yu. Morina
L. V. Bayunova
A. A. Bakhtuykov
E. A. Didenko
V. N. Sorokoumov
I. V. Romanova
A. O. Shpakov
author_facet K. V. Derkach
I. Yu. Morina
L. V. Bayunova
A. A. Bakhtuykov
E. A. Didenko
V. N. Sorokoumov
I. V. Romanova
A. O. Shpakov
author_sort K. V. Derkach
collection DOAJ
description 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: 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: 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: 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: 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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spelling doaj.art-4a0244e4053045088cf961accc79a4c82024-04-16T16:16:15ZengEndocrinology Research CentreОжирение и метаболизм2071-87132306-55242023-11-0120321722610.14341/omet1301810987Influence of metformin therapy and treatment with an allosteric luteinizing hormone agonist and chorionic gonadotropin on spermatogenesis in male rats with obesityK. V. Derkach0I. Yu. Morina1L. V. Bayunova2A. A. Bakhtuykov3E. A. Didenko4V. N. Sorokoumov5I. V. Romanova6A. O. Shpakov7I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of SciencesI.M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of SciencesI.M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of SciencesI.M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of SciencesI.M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences; Institute of Chemistry, St. Petersburg State UniversityI.M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences; Institute of Chemistry, St. Petersburg State UniversityI.M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of SciencesI.M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of SciencesBACKGROUND: 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: 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: 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: 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: 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.https://www.omet-endojournals.ru/jour/article/view/13018obesityspermatogenesismetforminluteinizing hormone receptorhuman chorionic gonadotropinallosteric agonisttestosterone
spellingShingle K. V. Derkach
I. Yu. Morina
L. V. Bayunova
A. A. Bakhtuykov
E. A. Didenko
V. N. Sorokoumov
I. V. Romanova
A. O. Shpakov
Influence of metformin therapy and treatment with an allosteric luteinizing hormone agonist and chorionic gonadotropin on spermatogenesis in male rats with obesity
Ожирение и метаболизм
obesity
spermatogenesis
metformin
luteinizing hormone receptor
human chorionic gonadotropin
allosteric agonist
testosterone
title Influence of metformin therapy and treatment with an allosteric luteinizing hormone agonist and chorionic gonadotropin on spermatogenesis in male rats with obesity
title_full Influence of metformin therapy and treatment with an allosteric luteinizing hormone agonist and chorionic gonadotropin on spermatogenesis in male rats with obesity
title_fullStr Influence of metformin therapy and treatment with an allosteric luteinizing hormone agonist and chorionic gonadotropin on spermatogenesis in male rats with obesity
title_full_unstemmed Influence of metformin therapy and treatment with an allosteric luteinizing hormone agonist and chorionic gonadotropin on spermatogenesis in male rats with obesity
title_short Influence of metformin therapy and treatment with an allosteric luteinizing hormone agonist and chorionic gonadotropin on spermatogenesis in male rats with obesity
title_sort influence of metformin therapy and treatment with an allosteric luteinizing hormone agonist and chorionic gonadotropin on spermatogenesis in male rats with obesity
topic obesity
spermatogenesis
metformin
luteinizing hormone receptor
human chorionic gonadotropin
allosteric agonist
testosterone
url https://www.omet-endojournals.ru/jour/article/view/13018
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