Modern aspects of biological modeling of sexual development disorders
Keywords:
premature puberty, girls, experimental model, rats
Abstract
Introduction. Studying pathogenetic mechanisms responsible for development of reproductive disorders in rat models is an important direction of modern pathophysiology. The rat has a functioning estrous cycle, a three-week gestation, and a hemochorial placentation. Biological modeling of endocrine gynecological pathology is based on cyclic changes in the ovaries and in the epithelium of the rat vagina. Currently, the development of an experimental model of puberty disorders in childhood is of interest. Premature puberty can lead to various pathological changes in future reproductive health. The relevance of this problem is obvious. The aim of this work was to study modern aspects of modeling premature puberty in girls. Method. Modern domestic and foreign reviews on the mechanism of premature puberty and experimental studies of modeling this pathology in experiments on rats were analyzed. Results. Premature puberty in girls is a disorder manifested by the development of one or all signs of puberty as early as before the age of 7 yrs. Sexual development is associated with characteristic roles of genetic and epigenetic factors. The latter traditionally include nutrition and stress as an adaptive reaction integrated with the activation of hormone synthesis. The nutrition factor is related with the functioning of adipose tissue hormones, including leptin, ghrelin, and the effects of insulin-like growth factor. A number of experimental studies on rats addressing effects of nutrition, stress, and light maladaptation on the reproductive system have demonstrated its significant effect on brain neurotransmitter systems. Regarding the mechanism of premature puberty, the least studied issue is the neuroendocrine regulation of the gonadal axis by the KISS/KISS1R system. Continuing study of the association between changes in the profile of monoamine neurotransmitters and the dynamics of kisspeptin in experiments on rats can expand understanding of sexual differentiation mechanisms in the brain. The obtained data can be translated into clinical practice for the management of premature puberty in girls. Conclusion. Due to the rare prevalence of premature puberty and insufficient data on its pathogenesis, this problem requires detailed study. It is necessary to further study the mechanism of this pathology by biological modeling on female rats at an early age.
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References
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9. Chebotareva Yu. Yu., Ovsiannikov V.G. Modeling of the polycystic ovary syndrome. Patologicheskaya fiziologiya i eksperimental’naya terapiya. 2009; 3: 29-31. (in Russian)
10. Chebotareva, Yu.Yu., Jurovskaja V.P., Ovsjannikov V.G., Method for modelling of polycystic ovaries. Patent RU 2337411 C1, RF; 2008.
11. Chebotareva Yu.Yu., Ovsjannikov V.G., Elesina I.G. Method for modeling chronic anovulation syndrome. Patent RU 2527166 C1, RF; 2014.
12.Savelieva G.M., Sukhikh G.T., Serov V.N., eds. Pathology of the reproductive system in childhood and adolescence. Gynecology. National guide.М.: «GEOTAR-Media”, 2019: 911-16. (in Russian)
13. Cantas-Orsdermir S, Eugster EA. Update in central precocious puberty: from etiologies to outcomes. Expert Rev Endocrinol Metab.2019; 1-8. doi: 10.1080/17446651.2019.1575726
14. Farkhutdinova L.M. Сentral precocious puberty. Archive of internal medicine. 2017; 7(4): 245 - 251. (In Russian). DOI: 10.20514/ 2226-6704-2017-7-4-245-251
15. Ersoy B, Kizilay D, Cayirli H, eds. Central Precocious Puberty Secondary to Adrenocortical Adenoma in a Female Child: Case Report and Review of the Literature. J Pediatr Adolesc Gynecol. 2017; 30(5): 591-594
16. Herrero-Morín J. D., González N. F., Crus L., eds. Hipertricocis cubital en una paciente co pubarquia precoz. Caso clínico. Arch Argent Pediatr. 2018;116(6): e765-e768
17.Chebotareva, Yu.Yu., Нashagulgova H.U. Some particularities of the non-specifical resistantion and the varientes of correction of premature thelarche. Kubanskii nauchnyi meditsinskii vestnik. 2009; 5 (110): 135-1. (In Russian)
18. Yurovskaya V.P., Savisko A.A., Chebotaryova Yu.Yu., eds. Pathogenetic peculiarities of premature thelarche. Pediatric and adolescent reproductive health. 2011; 2: 75-9. (In Russian)
19. Rodina M.A., Chebotaryova Yu.Yu., Prikhodko E. D., eds. Clinical features of the isosexual form of premature sexual development. Rossiyskiy vestnik perinatologii i pediatrii, 2019; 64 (4):298. (In Russian)
20. Bessa D. S., Maschietto M., eds. Methylome profiling of healthy and central precocious puberty girls. Clinical Epigenetics. 2018; 10:146
21. Gradone A, Cirilo G, Sasso M, eds. MKRN3 levels in girls with central precocious puberty and correlation with sexual hormone levels: a pilot study. Endocrine. 2018; 59(1):203-5
22. Tencer J., Lemaire P., Brailly-Tabard S., eds. Serum Inhibin B concentration as a predictor of age at first menstruation in girls with idiopathic central precocious puberty. PLoS ONE. 2018: 13(12): e0205810
23. Chernukha G. Ye., Tabeeva G. I., Gusev D. V., eds. Kisspeptin and Reproductive System. Gynecology Endocrinology. 2017; 3(132): 73-5. (in Russian)
24. Nikitina I.L., Bairamov A.A., Khoduleva Yu. N., Shabanov P.D. Kisspeptins in physiology and pathology of sex development — new diagnostic and therapeutic approaches. Reviews on clinical pharmacology and drug therapy. 2014; 12 (4): 3-12. (In Russian)
25. Gorelyshev A.S., Kuznetsova I.V. Menstrual Cycle and Energy ‘Policy’ of the Hypothalamus. Effective Pharmacotherapy Issue 5. Obstetrics and Gynecology. Special Issue «Actual Problems of Endocrine Gynecology». 2015; 5: 4-15. (In Russian)
26. Leka-Emiri S., Chrousos G.P., Kanaka-Gantenbein C. The mystery of puberty initiation: genetics and epigenetics of idiopathic central precocious puberty (ICPP). J Endocrinol Invest. 2017; 40(8): 789-802
Schneider Aguirre R., Eugster E. A. Central precocious puberty: From genetics to treatment. Best Practice & Research Clinical Endocrinology & metabolism. 2018; 32(4): 343-354
Hwang. Prevalence of Pathological Drain Lesions in Girls with Central Precocious Puberty: Possible Overestimation? J Korean Med Sci. 2018; 33(51):e329
29. Liyan Pan, Guangjian Liu, Xiaojian Mao, eds. Development of Prediction Models Using Machine Learning Algorithms for Girls with Suspected Central Precocious Puberty: Retrospective Study. JMIR Med Inform. 2019; 7 iss.I:e11728. - p1-13 DOI:10.2196/11728
30. Lopes M. C., Ramos C. O., eds. Applicability of a novel mathematical model for the prediction of adult height and age at menarche in girls with idiopathic central precocious puberty. Clinics. 2018; 73: 480
31. Schneider Aguirre R., Eugster E. A. Central precocious puberty: From genetics to treatment. Best Practice & Research Clinical Endocrinology & metabolism. 2018; 32(4): 343-354
32. Soriano-Guillén L., Argente J. Central precocious puberty, functional and tumor-related. Best Pract Res Clin Endocrinol Metab.2019; 10(19): 1521-6903
33. Sultan C., Gaspari L., Maimoun L., Kalfa N., Paris F. Disorders of puberty. Best Pract Res Clin Obstet Gyanaecol. 2018; 48:62-89
34. Limony Y., Koziel S., Friger M. Association between the onset age of puberty and parent height. PLoS ONE. 2018; 14(1): e0211334. PMID: 26020145 DOI: 10.1038/pr.2015.104
35. Burchakov D.I., Uspenskaya Y.B. The antioxidant, anti-inflammatory, and sedative effects of melatonin: results of clinical trials. Neuroscience and Behavioral Physiology. 2019; 49 (1): 54-59. (In Russian)
36. Burchakov D.I., Uspenskaya Y.B. The antioxidant, anti-inflammatory and sedative effects of melatonin: results of clinical trials. Neuroscience and Behavioral Physiology. 2019; 49(1): 54-59.
37. Zhukova O.V., Obukhova E.S., Khizhkin E.A., eds. Rats’ ovulatory function under melatonin receptors’ blockade. Uchenye zapiski Petrozavodskogo gosudarstvennogo universiteta. 2015; 8(153):98-104. (In Russian)
38. Zhukova O.V., Vinogradova I.A., Obukhova E.S., eds. Pharmacological blockade of the receptors of melatonin effect on ovulatory function in female rats under conditions of light deprivation. Experimental and Clinical Pharmacology. 2018; 81 (S): 84. (In Russian)
39. Zhukova O.V., Obukhova E.S., Hizhkin E.A., eds. Luzindole accelerates the aging of estrous function of female rats О.В. Жукова, Advances in gerontology. 2016; 29 (2): 279-6. (In Russian)
40. Obukhova E.S., Zhukova O.V., Hizhkin E.A., eds. The effect of light deprivation and luzindole on the ovulatory function in rats. Advances in Gerontology. 2017; 30(4): 529-4. (In Russian)
41. Vinogradova I.A., Goransky A.I., Zhukova O.V., eds. Participation of the melatoninergic system in the prevention of cancer and aging in light desynchronosis. In: White nights 2019. Materials of the V St. Petersburg International Oncological Forum: abstracts. Autonomous non-profit scientific and medical organization "Oncology Issues". St. Petersburg. 2019: 85-86. (In Russian)
42. Obukhova E.S., Zhukova O.V., Khizhkin E.A., eds. The effect of light deprivation and luzindole on the ovulatory function in rats. Advances in Gerontology. 2018; 8 (1): 22-25. (In Russian)
43. Zhukova O. V., Vinogradova I. A., Obukhova E. S., eds. A. Effect of pharmacological blockade of melatonin receptors on ovulatory function of female rats under conditions of light deprivation. Experimental and clinical pharmacology. 2018; 81(S): 84. (In Russian)
44. Vinogradova I.A., Ilyukha V.A., Yunash V.D., eds. Light desynchronosis as a risk factor of premature aging. Acta Naturae. 2016; 8(S1): 125-1.
45. Kuznetsova I.V., Burchakova M.N., Burchakov D.I., , eds. Psychogenic stress-dependent disorders of menstrual cycle: role of non-hormonal correction. Woman’s health. 2018; 10 (136): 68. (In Russian)
46. Nikitina I.L., Kudryashova E.K., Masel A., eds. Level of monoamine neurotransmitters in the central nervous system and kisspeptin in blood in the offsprings of experimentally induced model hyperandrogenisation in female rats. Pathological Physiology and Experimental Therapy, Russian journal. 2017; 61(1): 4-12. (In Russian)
47. Nikitina I.L., Yuchlina Yu.N., Vasileva E.Y., eds. Kisspeptin regulation of male sex development: possibilities of diagnosis and treatment of delayed puberty and hypogonadotropic hypogonadism. Problems of endocrinology.2018; 64 (5): 280-285. (In Russian)
DOI: 10.21626/vestnik/2019-1/13.
2. Chebotareva Yu.Yu, Podgornyy I.V, Ovsyannikov V.G., eds. The features of hormonal profile in rats of the SHR and WISTAR-KYOTO. Сrimean journal of experimental and clinical medicine. 2018; 8 (4): 42-5. (In Russian)
3. Chebotareva Yu.Yu., Ovsjannikov V.G., Khutiyeva M.Ya., Podgornyy I.V. The role of glucocorticoid dysregulation in the development of gestational pyelonephritis, placental insufficiency in the experiment. Nefrologiya. 2017; 21(5): 76-3. (in Russian)
4. Chebotareva Yu.Yu., Ovsjannikov V.G., Hutieva M.Ja., eds. The experimental modeling of the preeclampsia in the experiment in the Wistar rats. Vladikavkazskiy medikobiologicheskiy vestnik. 2013; 17(26): 50-53. (in Russian)
5. Chebotareva Yu.Yu., Ovsjannikov V.G., Letifov G. M., eds. Method for simulating gestational pyelonephritis. Patent RU 2532402 C1, RF; 2014. (in Russian)
6. Kriventsov M.A. Ontogenetic changes of the absolute and relative weight of the rats’ thymus after parenteral administration of xenogeneic cerebrospinal fluid. Ukrainskiy morfologicheskiy al’manakh. 2013; 11(2): 55-2. (in Russian)
7. Gelashvili O. A. Variant of periodization of biologically similar stages of human and rat ontogenesis. Saratovskiy nauchno-meditsinskiy zhurnal. 2008; 4 (4): 125-126. (in Russian)
8. Chebotareva Yu. Yu. Mechanisms of forming of policystic ovary syndrome during puberty, clinical course, prevention and treatment: diss. Rostov-on-Don; 2009, 409p. (in Russian)
9. Chebotareva Yu. Yu., Ovsiannikov V.G. Modeling of the polycystic ovary syndrome. Patologicheskaya fiziologiya i eksperimental’naya terapiya. 2009; 3: 29-31. (in Russian)
10. Chebotareva, Yu.Yu., Jurovskaja V.P., Ovsjannikov V.G., Method for modelling of polycystic ovaries. Patent RU 2337411 C1, RF; 2008.
11. Chebotareva Yu.Yu., Ovsjannikov V.G., Elesina I.G. Method for modeling chronic anovulation syndrome. Patent RU 2527166 C1, RF; 2014.
12.Savelieva G.M., Sukhikh G.T., Serov V.N., eds. Pathology of the reproductive system in childhood and adolescence. Gynecology. National guide.М.: «GEOTAR-Media”, 2019: 911-16. (in Russian)
13. Cantas-Orsdermir S, Eugster EA. Update in central precocious puberty: from etiologies to outcomes. Expert Rev Endocrinol Metab.2019; 1-8. doi: 10.1080/17446651.2019.1575726
14. Farkhutdinova L.M. Сentral precocious puberty. Archive of internal medicine. 2017; 7(4): 245 - 251. (In Russian). DOI: 10.20514/ 2226-6704-2017-7-4-245-251
15. Ersoy B, Kizilay D, Cayirli H, eds. Central Precocious Puberty Secondary to Adrenocortical Adenoma in a Female Child: Case Report and Review of the Literature. J Pediatr Adolesc Gynecol. 2017; 30(5): 591-594
16. Herrero-Morín J. D., González N. F., Crus L., eds. Hipertricocis cubital en una paciente co pubarquia precoz. Caso clínico. Arch Argent Pediatr. 2018;116(6): e765-e768
17.Chebotareva, Yu.Yu., Нashagulgova H.U. Some particularities of the non-specifical resistantion and the varientes of correction of premature thelarche. Kubanskii nauchnyi meditsinskii vestnik. 2009; 5 (110): 135-1. (In Russian)
18. Yurovskaya V.P., Savisko A.A., Chebotaryova Yu.Yu., eds. Pathogenetic peculiarities of premature thelarche. Pediatric and adolescent reproductive health. 2011; 2: 75-9. (In Russian)
19. Rodina M.A., Chebotaryova Yu.Yu., Prikhodko E. D., eds. Clinical features of the isosexual form of premature sexual development. Rossiyskiy vestnik perinatologii i pediatrii, 2019; 64 (4):298. (In Russian)
20. Bessa D. S., Maschietto M., eds. Methylome profiling of healthy and central precocious puberty girls. Clinical Epigenetics. 2018; 10:146
21. Gradone A, Cirilo G, Sasso M, eds. MKRN3 levels in girls with central precocious puberty and correlation with sexual hormone levels: a pilot study. Endocrine. 2018; 59(1):203-5
22. Tencer J., Lemaire P., Brailly-Tabard S., eds. Serum Inhibin B concentration as a predictor of age at first menstruation in girls with idiopathic central precocious puberty. PLoS ONE. 2018: 13(12): e0205810
23. Chernukha G. Ye., Tabeeva G. I., Gusev D. V., eds. Kisspeptin and Reproductive System. Gynecology Endocrinology. 2017; 3(132): 73-5. (in Russian)
24. Nikitina I.L., Bairamov A.A., Khoduleva Yu. N., Shabanov P.D. Kisspeptins in physiology and pathology of sex development — new diagnostic and therapeutic approaches. Reviews on clinical pharmacology and drug therapy. 2014; 12 (4): 3-12. (In Russian)
25. Gorelyshev A.S., Kuznetsova I.V. Menstrual Cycle and Energy ‘Policy’ of the Hypothalamus. Effective Pharmacotherapy Issue 5. Obstetrics and Gynecology. Special Issue «Actual Problems of Endocrine Gynecology». 2015; 5: 4-15. (In Russian)
26. Leka-Emiri S., Chrousos G.P., Kanaka-Gantenbein C. The mystery of puberty initiation: genetics and epigenetics of idiopathic central precocious puberty (ICPP). J Endocrinol Invest. 2017; 40(8): 789-802
Schneider Aguirre R., Eugster E. A. Central precocious puberty: From genetics to treatment. Best Practice & Research Clinical Endocrinology & metabolism. 2018; 32(4): 343-354
Hwang. Prevalence of Pathological Drain Lesions in Girls with Central Precocious Puberty: Possible Overestimation? J Korean Med Sci. 2018; 33(51):e329
29. Liyan Pan, Guangjian Liu, Xiaojian Mao, eds. Development of Prediction Models Using Machine Learning Algorithms for Girls with Suspected Central Precocious Puberty: Retrospective Study. JMIR Med Inform. 2019; 7 iss.I:e11728. - p1-13 DOI:10.2196/11728
30. Lopes M. C., Ramos C. O., eds. Applicability of a novel mathematical model for the prediction of adult height and age at menarche in girls with idiopathic central precocious puberty. Clinics. 2018; 73: 480
31. Schneider Aguirre R., Eugster E. A. Central precocious puberty: From genetics to treatment. Best Practice & Research Clinical Endocrinology & metabolism. 2018; 32(4): 343-354
32. Soriano-Guillén L., Argente J. Central precocious puberty, functional and tumor-related. Best Pract Res Clin Endocrinol Metab.2019; 10(19): 1521-6903
33. Sultan C., Gaspari L., Maimoun L., Kalfa N., Paris F. Disorders of puberty. Best Pract Res Clin Obstet Gyanaecol. 2018; 48:62-89
34. Limony Y., Koziel S., Friger M. Association between the onset age of puberty and parent height. PLoS ONE. 2018; 14(1): e0211334. PMID: 26020145 DOI: 10.1038/pr.2015.104
35. Burchakov D.I., Uspenskaya Y.B. The antioxidant, anti-inflammatory, and sedative effects of melatonin: results of clinical trials. Neuroscience and Behavioral Physiology. 2019; 49 (1): 54-59. (In Russian)
36. Burchakov D.I., Uspenskaya Y.B. The antioxidant, anti-inflammatory and sedative effects of melatonin: results of clinical trials. Neuroscience and Behavioral Physiology. 2019; 49(1): 54-59.
37. Zhukova O.V., Obukhova E.S., Khizhkin E.A., eds. Rats’ ovulatory function under melatonin receptors’ blockade. Uchenye zapiski Petrozavodskogo gosudarstvennogo universiteta. 2015; 8(153):98-104. (In Russian)
38. Zhukova O.V., Vinogradova I.A., Obukhova E.S., eds. Pharmacological blockade of the receptors of melatonin effect on ovulatory function in female rats under conditions of light deprivation. Experimental and Clinical Pharmacology. 2018; 81 (S): 84. (In Russian)
39. Zhukova O.V., Obukhova E.S., Hizhkin E.A., eds. Luzindole accelerates the aging of estrous function of female rats О.В. Жукова, Advances in gerontology. 2016; 29 (2): 279-6. (In Russian)
40. Obukhova E.S., Zhukova O.V., Hizhkin E.A., eds. The effect of light deprivation and luzindole on the ovulatory function in rats. Advances in Gerontology. 2017; 30(4): 529-4. (In Russian)
41. Vinogradova I.A., Goransky A.I., Zhukova O.V., eds. Participation of the melatoninergic system in the prevention of cancer and aging in light desynchronosis. In: White nights 2019. Materials of the V St. Petersburg International Oncological Forum: abstracts. Autonomous non-profit scientific and medical organization "Oncology Issues". St. Petersburg. 2019: 85-86. (In Russian)
42. Obukhova E.S., Zhukova O.V., Khizhkin E.A., eds. The effect of light deprivation and luzindole on the ovulatory function in rats. Advances in Gerontology. 2018; 8 (1): 22-25. (In Russian)
43. Zhukova O. V., Vinogradova I. A., Obukhova E. S., eds. A. Effect of pharmacological blockade of melatonin receptors on ovulatory function of female rats under conditions of light deprivation. Experimental and clinical pharmacology. 2018; 81(S): 84. (In Russian)
44. Vinogradova I.A., Ilyukha V.A., Yunash V.D., eds. Light desynchronosis as a risk factor of premature aging. Acta Naturae. 2016; 8(S1): 125-1.
45. Kuznetsova I.V., Burchakova M.N., Burchakov D.I., , eds. Psychogenic stress-dependent disorders of menstrual cycle: role of non-hormonal correction. Woman’s health. 2018; 10 (136): 68. (In Russian)
46. Nikitina I.L., Kudryashova E.K., Masel A., eds. Level of monoamine neurotransmitters in the central nervous system and kisspeptin in blood in the offsprings of experimentally induced model hyperandrogenisation in female rats. Pathological Physiology and Experimental Therapy, Russian journal. 2017; 61(1): 4-12. (In Russian)
47. Nikitina I.L., Yuchlina Yu.N., Vasileva E.Y., eds. Kisspeptin regulation of male sex development: possibilities of diagnosis and treatment of delayed puberty and hypogonadotropic hypogonadism. Problems of endocrinology.2018; 64 (5): 280-285. (In Russian)
Published
2021-12-11
How to Cite
Chebotaryova Y. Y., Ovsyannikov V., Rodina M., Podgorny I., Hutieva M. Modern aspects of biological modeling of sexual development disorders // Patologicheskaya Fiziologiya i Eksperimental’naya Terapiya (Pathological physiology and experimental therapy). 2021. VOL. 65. № 4. PP. 128–136.
Issue
Section
Methods
