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ISSN 0023-4885 * The journal was founded in 1910. * It is included in the list of HAC
Krolikovodstvo i Zverovodstvo
Rabbit breeding and fur farming international interdisciplinary journal

ПОТЕНЦИАЛЬНАЯ РОЛЬ КИССПЕПТИНА В РЕГУЛЯЦИИ РЕПРОДУКТИВНОЙ ФУНКЦИИ

УДК 577.21                                                            DOI: 10.52178/00234885_2026_1_42

ПОТЕНЦИАЛЬНАЯ РОЛЬ КИССПЕПТИНА В РЕГУЛЯЦИИ РЕПРОДУКТИВНОЙ ФУНКЦИИ

Гормоны, кисспептины, имплантация

Дмитрий Владимирович  Попов, Дарья Дмитриевна Исакова*, Глеб Юрьевич Косовский

Федеральное государственное бюджетное научное учреждение «Научно-исследовательский институт пушного звероводства и кролиководства имени В.А. Афанасьева»

Россия, 140143, Московская область, Раменский район, пгт. Родники, ул. Трудовая, 6

*e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

    В настоящей статье приведены данные о физиологической роли кисспептина в регуляции репродуктивной функции. Кисспептин – это нейропептид гипоталамуса, кодируемый геном KISS1. Приведенные данные показали, что кисспептин способен контролировать как пульсирующее, так и скачкообразное высвобождение ГнРГ, играя фундаментальные роли в репродукции, которые включают секрецию гонадотропинов, овуляцию и метаболическую регуляцию фертильности. Кроме того, недавние исследования продемонстрировали участие системы кисспептина в процессах имплантации и плацентации. В этой статье обобщены современные знания о патофизиологии этих локальных плацентарных регуляторных факторов в качестве потенциальных биомаркеров на стадии оплодотворения и эмбриогенеза.

Ключевые слова: кисспептин, искусственное осеменение, оплодотворение, эмбриогенез.

Конфликт интересов. Авторы заявляют об отсутствии конфликта интересов.

Вклад авторов. Д.В. Попов – написание статьи, сбор и обработка материала; Д.Д. Исакова – написание статьи, сбор и обработка материала; Г.Ю. Косовский – руководство, редактирование текста.

Информация об авторах:

Попов Дмитрий Владимирович – кандидат биологических наук, ведущий научный сотрудник, заведующий отделом биотехнологии ФГБНУ НИИПЗК, SPIN-код: 3657-4880; ORCID: 0000-0001-7422-5470, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

Исакова Дарья Дмитриевна – ветеринарный врач, аспирант ФГБНУ НИИПЗК, SPIN-код: 1811-2672; AuthorID: 823437; ORCID: 0009-0000-9113-3607, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

Косовский Глеб Юрьевич – доктор биологических наук, член-корреспондент РАН, директор ФГБНУ НИИПЗК, SPIN-код: 3736-3480; AuthorID: 353097; ORCID:0000-0003-3808-3086; ResearcherID: ABG-7304-2020; ScopusID: 57196461206.

Список литературы

  1. Lee JH, Miele ME, Hicks DJ, et KiSS-1, a novel human malignant melanoma metastasis-suppressor gene. J Natl Cancer Inst. 1996;88(23):1731-1737. [DOI: 10.1093/jnci/88.23.1731]
  2. de Roux N, Genin E, Carel JC, Matsuda F, Chaussain JL, Milgrom Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proc Natl Acad Sci U S A. 2003;100(19):1097210976. [DOI: 10.1073/pnas.1834399100].
  3. Seminara SB, Messager S, Chatzidaki EE, et al. The GPR54 gene as a regulator of puberty. N Engl J Med. 2003;349(17):1614-1627. [DOI: 10.1056/NEJMoa035322]
  4. Funes S, Hedrick JA, Vassileva G, et The KiSS-1 receptor GPR54 is essential for the development of the murine reproductive system. Biochem Biophys Res Commun. 2003;312(4):1357-1363.[DOI: 10.1016/j.bbrc.2003.11.066]
  5. Kotani M, Detheux M, Vandenbogaerde A, et al. The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. J Biol Chem. 2001;276(37):34631-34636. [DOI: 1074/jbc.M104847200]
  6. Ohtaki T, Shintani Y, Honda S, et al. Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-proteincoupled Nature. 2001;411(6837):613-617. [DOI: 10.1038/35079135]
  7. Muir AI, Chamberlain L, Elshourbagy NA, et AXOR12, a novel human G protein-coupled receptor, activated by the peptide KiSS-1. J Biol Chem. 2001;276(31):2896928975. [DOI: 10.1074/jbc.M102743200]
  8. Gottsch ML, Cunningham MJ, Smith JT, et al. A role for kisspeptins in the regulation of gonadotropin secretion in the mouse. 2004;145(9):4073-4077.[DOI: 10.1210/en.2004-0431]
  9. Irwig MS, Fraley GS, Smith JT, et Kisspeptin activation of gonadotropin releasing hormone neurons and regulation of KiSS-1 mRNA in the male rat. Neuroendocrinology. 2004;80(4):264-272.[DOI: 10.1159/000083140]
  10. Messager S, Chatzidaki EE, Ma D, et Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54. Proc Natl Acad Sci U S A. 2005;102(5):1761-1766. [DOI: 10.1073/pnas.0409330102]
  11. Shahab M, Mastronardi C, Seminara SB, Crowley WF, Ojeda SR, Plant TM.Increased hypothalamic GPR54 signaling: a potential mechanism for initiation of puberty in primates. Proc Natl Acad Sci U S A. 2005;102(6):21292134. [DOI: 10.1073/pnas.0409822102]
  12. Smith JT, Cunningham MJ, Rissman EF, Clifton DK, Steiner Regulation of Kiss1 gene expression in the brain of the female mouse. Endocrinology. 2005;146(9):3686-3692. [DOI: 10.1210/en.2005-0488]
  13. Dhillo WS, Chaudhri OB, Patterson M, et Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males. J Clin Endocrinol Metab. 2005;90(12):6609-6615.[DOI: 10.1210/jc.2005-1468]
  14. Clarkson J, d’Anglemont de Tassigny X, Colledge WH, Caraty A, Herbison AE. Distribution of kisspeptin neurones in the adult female mouse brain. J Neuroendocrinol. 2009;21(8):673[DOI: 10.1111/j.1365-2826.2009.01892.x]
  15. Gottsch ML, Cunningham MJ, Smith JT, et al. A role for kisspeptins in the regulation of gonadotropin secretion in the Endocrinology. 2004;145(9):4073-4077. (DOI: 10.1210/en.2004-0431)
  16. Castellano JM, Gaytan M, Roa J, et al. Expression of KiSS-1 in rat ovary: putative local regulator of ovulation. Endocrinology. 2006;147(10):4852-4862. [DOI: 10.1210/ 2006-0117]
  17. Messager S, Chatzidaki EE, Ma D, et Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54. Proc Natl Acad Sci U S A. 2005;102(5):1761-1766. [DOI: 10.1073/pnas.0409330102].
  18. Clarkson J, d’Anglemont de Tassigny X, Moreno AS, Colledge WH, Herbison AE. Kisspeptin-GPR54 signaling is essential for preovulatory gonadotropin-releasing hormone neuron activation and the luteinizing hormone surge. J 2008;28(35):8691-8697. [DOI: 10.1523/ JNEUROSCI.1775-08.2008].
  19. Song WJ, Mondal P, Wolfe A, et al. Glucagon regulates hepatic kisspeptin to impair insulin secretion. Cell Metab. 2014;19(4):667-681. [DOI: 10.1016/j.cmet.2014.03.005].
  20. Callejas J, Párrizas M, Maestro MA, et al. Expression of the kisspeptin/KISS1R system in murine and human pancreatic β-cells and its relation to the gestational metabolic status. Endocr Connect. 2021;10(10):1243-1255. [DOI: 1530/EC-21-0243].
  21. Park DW, Lee SK, Hong SR, et Expression of Kisspeptin and its receptor GPR54 in the first trimester trophoblast of women with recurrent pregnancy loss. Am J Reprod Immunol. 2012;67(2):132-139. [DOI: 10.1111/j.16000897.2011.01072.x].
  22. Gallos ID, Sivakumaran S, Thangaratinam S, et al.Maternal plasma kisspeptin in the first trimester of pregnancy: a novel biomarker of placental function and fetal growth. Reprod Sci. 2013;20(3):286-292. [DOI: 1177/1933719112459221].
  23. Jayasena CN, Abbara A, Izzi-Engbeaya C, et al.Reduced levels of plasma kisspeptin during the antenatal booking visit are associated with increased risk of miscarriage. J Clin Endocrinol 2014;99(12):E2652-E2660. [DOI: 10.1210/jc.2014-1953].
  24. Horikoshi Y, Matsumoto H, Takatsu Y, et al. Dramatic elevation of plasma metastin concentrations in human pregnancy: metastin as a novel placenta-derived hormone in humans. J Clin Endocrinol Metab. 2003;88(2):914[DOI: 10.1210/jc.2002-021235].

POTENTIAL ROLE OF KISSPEPTIN IN THE REGULATION OF REPRODUCTIVE FUNCTION

Hormones, kisspeptins, implantation

Dmitry Vladimirovich Popov, Darya Dmitrievna Isakova*, Gleb Yurievich Kosovsky

Federal State Budget Scientific Institute «Scientific Research Institute of Fur – Bearing Animal Breeding and Rabbit Breeding named after V.A. Afanas`ev»

Russia, 140143, Moscow region, Ramenskoye district, pgt. Rodniky, Trudovaya str., 6

*e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

   This article presents data on the physiological role of kisspeptin in the regulation of reproductive function. Kisspeptin is a hypothalamic neuropeptide encoded by the KISS1 gene. The data presented show that kisspeptin is capable of controlling both pulsatile and surge release of GnRH, playing fundamental roles in reproduction, including gonadotropin secretion, ovulation, and metabolic regulation of fertility. In addition, recent studies have demonstrated the involvement of the kisspeptin system in implantation and placentation processes. This article summarizes current knowledge on the pathophysiology of these local placental regulatory factors as potential biomarkers at the stage of fertilization and embryogenesis.

Keywords: kisspeptin, artificial insemination, fertilization, embryogenesis.

Conflict of interest. The authors declare no conflict of interest.

Contribution of the authors. D.V. Popov – writing the article, collecting and processing the material; D.D. Isakova – writing the article, collecting and processing the material; G.Yu. Kosovsky – management, text editing.

Information about the authors:

Popov Dmitry Vladimirovich – Candidate of Biological Sciences, Leading Researcher, Head of Biotechnology Department, of the Afanas`ev Research Institute of Fur – Bearing Animal Breeding and Rabbit Breeding, SPIN-code 3657-4880, ORCID: 0000-0001-7422-5470, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

Isakova Darya Dmitrievna– Veterinarian, post-graduate student of the Afanas`ev Research Institute of Fur – Bearing Animal Breeding and Rabbit Breeding, SPIN-code: 1811-2672, Author ID: 823437, ORCID: 0009-0000-9113-3607, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

Kosovsky Gleb Yurievich – Doctor of Science in Biology, Corresponding Member of the Russian Academy of Sciences, the Head of the Afanas`ev Research Institute of Fur – Bearing Animal Breeding and Rabbit Breeding, SPIN-code: 3736-3480, AuthorID: 353097, ORCID: 0000-0003-3808-3086, ResearcherID: ABG-7304-2020; ScopusID: 57196461206.

References:

  1. Lee JH, Miele ME, Hicks DJ, et KiSS-1, a novel human malignant melanoma metastasis-suppressor gene. J Natl Cancer Inst. 1996;88(23):1731-1737. [DOI: 10.1093/jnci/88.23.1731]
  2. de Roux N, Genin E, Carel JC, Matsuda F, Chaussain JL, Milgrom Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proc Natl Acad Sci U S A. 2003;100(19):1097210976. [DOI: 10.1073/pnas.1834399100].
  3. Seminara SB, Messager S, Chatzidaki EE, et al. The GPR54 gene as a regulator of puberty. N Engl J Med. 2003;349(17):1614-1627. [DOI: 10.1056/NEJMoa035322]
  4. Funes S, Hedrick JA, Vassileva G, et The KiSS-1 receptor GPR54 is essential for the development of the murine reproductive system. Biochem Biophys Res Commun. 2003;312(4):1357-1363.[DOI: 10.1016/j.bbrc.2003.11.066]
  5. Kotani M, Detheux M, Vandenbogaerde A, et al. The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. J Biol Chem. 2001;276(37):34631-34636. [DOI: 1074/jbc.M104847200]
  6. Ohtaki T, Shintani Y, Honda S, et al. Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-proteincoupled Nature. 2001;411(6837):613-617. [DOI: 10.1038/35079135]
  7. Muir AI, Chamberlain L, Elshourbagy NA, et AXOR12, a novel human G protein-coupled receptor, activated by the peptide KiSS-1. J Biol Chem. 2001;276(31):2896928975. [DOI: 10.1074/jbc.M102743200]
  8. Gottsch ML, Cunningham MJ, Smith JT, et al. A role for kisspeptins in the regulation of gonadotropin secretion in the mouse. 2004;145(9):4073-4077.[DOI: 10.1210/en.2004-0431]
  9. Irwig MS, Fraley GS, Smith JT, et Kisspeptin activation of gonadotropin releasing hormone neurons and regulation of KiSS-1 mRNA in the male rat. Neuroendocrinology. 2004;80(4):264-272.[DOI: 10.1159/000083140]
  10. Messager S, Chatzidaki EE, Ma D, et Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54. Proc Natl Acad Sci U S A. 2005;102(5):1761-1766. [DOI: 10.1073/pnas.0409330102]
  11. Shahab M, Mastronardi C, Seminara SB, Crowley WF, Ojeda SR, Plant TM.Increased hypothalamic GPR54 signaling: a potential mechanism for initiation of puberty in primates. Proc Natl Acad Sci U S A. 2005;102(6):21292134. [DOI: 10.1073/pnas.0409822102]
  12. Smith JT, Cunningham MJ, Rissman EF, Clifton DK, Steiner Regulation of Kiss1 gene expression in the brain of the female mouse. Endocrinology. 2005;146(9):3686-3692. [DOI: 10.1210/en.2005-0488]
  13. Dhillo WS, Chaudhri OB, Patterson M, et Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males. J Clin Endocrinol Metab. 2005;90(12):6609-6615.[DOI: 10.1210/jc.2005-1468]
  14. Clarkson J, d’Anglemont de Tassigny X, Colledge WH, Caraty A, Herbison AE. Distribution of kisspeptin neurones in the adult female mouse brain. J Neuroendocrinol. 2009;21(8):673[DOI: 10.1111/j.1365-2826.2009.01892.x]
  15. Gottsch ML, Cunningham MJ, Smith JT, et al. A role for kisspeptins in the regulation of gonadotropin secretion in the Endocrinology. 2004;145(9):4073-4077. (DOI: 10.1210/en.2004-0431)
  16. Castellano JM, Gaytan M, Roa J, et al. Expression of KiSS-1 in rat ovary: putative local regulator of ovulation. Endocrinology. 2006;147(10):4852-4862. [DOI: 10.1210/ 2006-0117]
  17. Messager S, Chatzidaki EE, Ma D, et Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54. Proc Natl Acad Sci U S A. 2005;102(5):1761-1766. [DOI: 10.1073/pnas.0409330102].
  18. Clarkson J, d’Anglemont de Tassigny X, Moreno AS, Colledge WH, Herbison AE. Kisspeptin-GPR54 signaling is essential for preovulatory gonadotropin-releasing hormone neuron activation and the luteinizing hormone surge. J 2008;28(35):8691-8697. [DOI: 10.1523/ JNEUROSCI.1775-08.2008].
  19. Song WJ, Mondal P, Wolfe A, et al. Glucagon regulates hepatic kisspeptin to impair insulin secretion. Cell Metab. 2014;19(4):667-681. [DOI: 10.1016/j.cmet.2014.03.005].
  20. Callejas J, Párrizas M, Maestro MA, et al. Expression of the kisspeptin/KISS1R system in murine and human pancreatic β-cells and its relation to the gestational metabolic status. Endocr Connect. 2021;10(10):1243-1255. [DOI: 1530/EC-21-0243].
  21. Park DW, Lee SK, Hong SR, et Expression of Kisspeptin and its receptor GPR54 in the first trimester trophoblast of women with recurrent pregnancy loss. Am J Reprod Immunol. 2012;67(2):132-139. [DOI: 10.1111/j.16000897.2011.01072.x].
  22. Gallos ID, Sivakumaran S, Thangaratinam S, et al.Maternal plasma kisspeptin in the first trimester of pregnancy: a novel biomarker of placental function and fetal growth. Reprod Sci. 2013;20(3):286-292. [DOI: 1177/1933719112459221].
  23. Jayasena CN, Abbara A, Izzi-Engbeaya C, et al.Reduced levels of plasma kisspeptin during the antenatal booking visit are associated with increased risk of miscarriage. J Clin Endocrinol 2014;99(12):E2652-E2660. [DOI: 10.1210/jc.2014-1953].
  24. Horikoshi Y, Matsumoto H, Takatsu Y, et al. Dramatic elevation of plasma metastin concentrations in human pregnancy: metastin as a novel placenta-derived hormone in humans. J Clin Endocrinol Metab. 2003;88(2):914[DOI: 10.1210/jc.2002-021235].