Changes in progesterone and gonadoliberin levels after introduction of exogenous kisspeptin in Danio rerio females
Alexandra A. Blazhenko , Marina I. Kostina , Alina A. Nuzhnova
Medical academic journal ›› 2025, Vol. 25 ›› Issue (1) : 31 -41.
Changes in progesterone and gonadoliberin levels after introduction of exogenous kisspeptin in Danio rerio females
BACKGROUND: According to modern concepts, the kisspeptin signaling system is the upper (central) link in the regulation of reproductive function. The neuropeptide kisspeptin is considered an indicator of a number of obstetric pathologies in humans. Therefore, it should be considered important to search for new synthetic analogues of natural kisspeptins as pharmacological agents of reproduction regulation. On the other hand, it should also be considered important to search for new effective model organisms in which certain effects manifest themselves most prominently compared to traditional experimental animals.
AIM: To quantify the effect of kisspeptin-14 on the level of gonadoliberin and progesterone in two doses, at the time typical for the action of neuropeptides, on the model organism Danio rerio.
METHODS: In this study, an analogue of kisspeptin, conventionally designated kisspeptin-14, was used. All Danio rerio females had reached puberty by the time of the experiment (6–8 months). Kisspeptin was administered in doses of 1 and 4 ng. The groups were analyzed 1 and 4 hours after administration. Before administration of the preparations, the fish were subjected to lidocaine anesthesia at a concentration of 40 mg/l for 5–6 minutes, then the drug was administered intracerebroventrically. After waiting for 1 or 4 hours, the material was collected (gonads and midbrain). Gonad and midbrain samples were homogenized, homogenates were suspended, and enzyme immunoassay was performed to determine hormone concentrations.
RESULTS: Administration of kisspeptin-14 at a dose of 1 ng led to an increase in gonadoliberin levels 4 hours after administration. With a shorter time after administration, no statistically significant results were found. Administration of kisspeptin-14 at doses of 1 and 4 ng led to an increase in progesterone levels in the gonads of Danio rerio females 1 and 4 hours after administration. At the same time, statistically significant differences compared with the control group were noted at different sample collection dates.
CONCLUSION: Intracerebroventricular administration of the kisspeptin-14 at a dose of 1 ng after 4 hours causes an increase in gonadoliberin in the structures of the midbrain. Intracerebroventricular administration of kisspeptin-14 causes an increase in progesterone in the gonads of Danio rerio females. There was no unambiguous relationship between changes in the concentration of gonadoliberin in the structures of the midbrain and changes in the concentration of progesterone in the gonads of females.
Danio rerio / kisspeptin / progesterone / gonadoliberin / zebrafish
| [1] |
Patent of the Russian Federation for invention № 2766689 / 15.03.2022. Bull. N 8. Blazhenko AA, Khokhlov PP, Lebedev AA, Shabanov PD. The use of lidocaine for anesthesia of a Danio rerio model organism under experimental conditions. (In Russ.) |
| [2] |
Патент РФ на изобретение № 2766689 / 15.03.2022. Бюл. № 8. Блаженко А.А., Хохлов П.П., Лебедев А.А., и др. Применение лидокаина для анестезии модельного организма Danio rerio в экспериментальных условиях. |
| [3] |
Pinilla L, Aguilar E, Dieguez C, et al. Kisspeptins and reproduction: physiological roles and regulatory mechanisms. Physiol Rev. 2012;3(92):1235–1316. doi: 10.1152/physrev.00037.2010 |
| [4] |
Pinilla L., Aguilar E., Dieguez C., et al. Kisspeptins and reproduction: physiological roles and regulatory mechanisms // Physiol Rev. 2012. Vol. 3, N 92. P. 1235–1316. doi: 10.1152/physrev.00037.2010 |
| [5] |
Chernukha GE, Tabeeva GI, Gusev DV, Shmakov RG. Kisspeptin and the reproductive system. Doctor.ru. 2017;132(3):73–78. EDN: YPQGIF (In Russ.) |
| [6] |
Чернуха Г.Е., Табеева Г.И., Гусев Д.В., Шмаков Р.Г. Кисспептин и репродуктивная система // Доктор.Ру. 2017. Т. 132, № 3. С. 73–78. EDN: YPQGIF |
| [7] |
George JT, Veldhuis JD, Roseweir AK, et al. Kisspeptin-10 is a potent stimulator of LH and increases pulse frequency in men. J Clin Endocrinol Metab. 2011;8(96):1228–1236. doi: 10.1210/jc.2011-0089 |
| [8] |
George J.T., Veldhuis J.D., Roseweir A.K., et al. Kisspeptin-10 is a potent stimulator of LH and increases pulse frequency in men // J Clin Endocrinol Metab. 2011. Vol. 8, N 96. P. 1228–1236. doi: 10.1210/jc.2011-0089 |
| [9] |
Wang B, Mechaly AS, Somoza GM. Overview and new insights into the diversity, evolution, role, and regulation of kisspeptins and their receptors in teleost fish. Front Endocrinol. 2022;13:862614. doi: 10.3389/fendo.2022.862614 |
| [10] |
Wang B., Mechaly A.S., Somoza G.M. Overview and new insights into the diversity, evolution, role, and regulation of kisspeptins and their receptors in teleost fish // Front Endocrinol. 2022. Vol. 13. P. 862614. doi: 10.3389/fendo.2022.862614 |
| [11] |
Ogawa S, Parhar IS. Biological significance of kisspeptin – Kiss 1 receptor signaling in the habenula of teleost species. Front Endocrinol (Lausanne). 2018;9:222. doi: 10.3389/fendo.2018.00222 |
| [12] |
Ogawa S., Parhar I.S. Biological significance of kisspeptin – Kiss 1 receptor signaling in the habenula of teleost species // Front Endocrinol (Lausanne). 2018. Vol. 9. P. 222. doi: 10.3389/fendo.2018.00222 |
| [13] |
Kitahashi T, Ogawa S, Parhar IS. Cloning and expression of kiss2 in the zebrafish and medaka. Endocrinology. 2009;150(2):821–831. doi: 10.1210/en.2008-0940 |
| [14] |
Kitahashi T., Ogawa S., Parhar I.S. Cloning and expression of kiss2 in the zebrafish and medaka // Endocrinology. 2009. Vol. 150, N 2. P. 821–831. doi: 10.1210/en.2008-0940 |
| [15] |
Ogawa S, Ng KW, Ramadasan PN, et al. Habenular Kiss1 neurons modulate the serotonergic system in the brain of zebrafish. Endocrinology. 2012;153(5):2398–2407. doi: 10.1210/en.2012-1062 |
| [16] |
Ogawa S., Ng K.W., Ramadasan P.N., et al. Habenular Kiss1 neurons modulate the serotonergic system in the brain of zebrafish // Endocrinology. 2012. Vol. 153, N 5. P. 2398–2407. doi: 10.1210/en.2012-1062 |
| [17] |
Onuma TA, Duan C. Duplicated Kiss1 receptor genes in zebrafish: distinct gene expression patterns, different ligand selectivity, and a novel nuclear isoform with transactivating activity. FASEB J. 2012;26(7):2941–2950. doi: 10.1096/fj.11-201095 |
| [18] |
Onuma T.A., Duan C. Duplicated Kiss1 receptor genes in zebrafish: distinct gene expression patterns, different ligand selectivity, and a novel nuclear isoform with transactivating activity // FASEB J. 2012. Vol. 26, N 7. P. 2941–2950. doi: 10.1096/fj.11-201095 |
| [19] |
Zhao Y, Lin MC, Mock A, et al. Kisspeptins modulate the biology of multiple populations of gonadotropin-releasing hormone neurons during embryogenesis and adulthood in zebrafish (Danio rerio). PLoS One. 2014;9(8):e104330. doi: 10.1371/journal.pone.0104330 |
| [20] |
Zhao Y., Lin M.C., Mock A., et al. Kisspeptins modulate the biology of multiple populations of gonadotropin-releasing hormone neurons during embryogenesis and adulthood in zebrafish (Danio rerio) // PLoS One. 2014. Vol. 9, N 8. P. e104330. doi: 10.1371/journal.pone.0104330 |
| [21] |
Matsui H, Takatsu Y, Kumano S, et al. Peripheral administration of metastin induces marked gonadotropin release and ovulation in the rat. Biochem Biophys Res Commun. 2004;320(2):383–388. doi: 10.1016/j.bbrc.2004.05.185 |
| [22] |
Matsui H., Takatsu Y., Kumano S., et al. Peripheral administration of metastin induces marked gonadotropin release and ovulation in the rat // Biochem Biophys Res Commun. 2004. Vol. 320, N 2. P. 383–388. doi: 10.1016/j.bbrc.2004.05.185 |
| [23] |
Gottsch ML, Cunningham MJ, Smith JT, et al. A role for kisspeptins in the regulation of gonadotropin secretion in the mouse. Endocrinology. 2004;145(9):4073–4077. doi: 10.1210/en.2004-0431 |
| [24] |
Gottsch M.L., Cunningham M.J., Smith J.T., et al. A role for kisspeptins in the regulation of gonadotropin secretion in the mouse // Endocrinology. 2004. Vol. 145, N 9. P. 4073–4077. doi: 10.1210/en.2004-0431 |
| [25] |
Shahab M, Mastronardi C, Seminara SB, et al. Increased hypothalamic GPR54 signaling: a potential mechanism for initiation of puberty in primates. Proc Natl Acad Sci USA. 2005;102(6):2129–2134. doi: 10.1073/pnas.0409822102 |
| [26] |
Shahab M., Mastronardi C., Seminara S.B., et al. Increased hypothalamic GPR54 signaling: a potential mechanism for initiation of puberty in primates // Proc Natl Acad Sci USA. 2005. Vol. 102, N 6. P. 2129–2134. doi: 10.1073/pnas.0409822102 |
| [27] |
Messager S, Chatzidaki EE, Ma D, et al. Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54. Proc Natl Acad Sci USA. 2005;102(5):1761–1766. doi: 10.1016/j.bbrc.2004.05.185 |
| [28] |
Messager S., Chatzidaki E.E., Ma D., et al. Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54 // Proc Natl Acad Sci USA. 2005. Vol. 102, N 5. P. 1761–1766. doi: 10.1016/j.bbrc.2004.05.185 |
| [29] |
Sitticharoon C, Sririwichitchai R, Keadkraichaiwat I, et al. ODP417 Kisspeptin directly stimulates estrogen and progesterone secretion from human granulosa cells. J Endocr Soc. 2022;6:663–664. doi: 10.1210/jendso/bvac150.1373 |
| [30] |
Sitticharoon C., Sririwichitchai R., Keadkraichaiwat I., et al. ODP417 Kisspeptin directly stimulates estrogen and progesterone secretion from human granulosa cells // J Endocr Soc. 2022. Vol. 6. P. 663–664. doi: 10.1210/jendso/bvac150.1373 |
| [31] |
Guo L, Xu H, Li Y, et al. Kisspeptin-10 promotes progesterone synthesis in bovine ovarian granulosa cells via downregulation of microRNA-1246. Genes. 2022;13(2):298–310. doi: 10.3390/genes13020298 |
| [32] |
Guo L., Xu H., Li Y., et al. Kisspeptin-10 promotes progesterone synthesis in bovine ovarian granulosa cells via downregulation of microRNA-1246 // Genes. 2022. Vol. 13, N 2. P. 298–310. doi: 10.3390/genes13020298 |
| [33] |
Xiao Y, Ni Y, Huang Y, et al. Effects of kisspeptin-10 on progesterone secretion in cultured chicken ovarian granulosa cells from preovulatory (F1–F3) follicles. Peptides. 2011;32(10):2091–2097. doi: 10.1016/j.peptides.2011.09.001 |
| [34] |
Xiao Y., Ni Y., Huang Y., et al. Effects of kisspeptin-10 on progesterone secretion in cultured chicken ovarian granulosa cells from preovulatory (F1–F3) follicles // Peptides. 2011. Vol. 32, N 10. P. 2091–2097. doi: 10.1016/j.peptides.2011.09.001 |
| [35] |
Khokhlov PP, Blazhenko AA, Komlev AS, et al. Synthetic analogues of kisspeptin peptides have pharmacological properties of natural peptides. Experimental and clinical pharmacology. 2023;86(11S):153–154. EDN: MOWCYR doi: 10.30906/ekf-2023-86s-153a |
| [36] |
Хохлов П.П., Блаженко А.А., Комлев А.С., и др. Синтетические аналоги пептидов кисспептинов обладают фармакологическими свойствами природных пептидов // Экспериментальная и клиническая фармакология. 2023. Т. 86, № 11S. С. 153–154. EDN: MOWCYR doi: 10.30906/ekf-2023-86s-153a |
| [37] |
Ogawa S, Nathan FM, Parhar IS. Habenular kisspeptin modulates fear in the zebrafish. Proc Natl Acad Sci USA. 2014;111(10):3841–3846. doi: 10.1073/pnas.1314184111 |
| [38] |
Ogawa S., Nathan F.M., Parhar I.S. Habenular kisspeptin modulates fear in the zebrafish // Proc Natl Acad Sci USA. 2014. Vol. 111, N 10. P. 3841–3846. doi: 10.1073/pnas.1314184111 |
| [39] |
Karaman GE, Emekli-Alturfan E, Akyüz S. Zebrafish; an emerging model organism for studying toxicity and biocompatibility of dental materials. Cell Mol Biol (Noisy-le-Grand). 2020;66(8):41–46. |
| [40] |
Karaman G.E., Emekli-Alturfan E., Akyüz S. Zebrafish; an emerging model organism for studying toxicity and biocompatibility of dental materials // Cell Mol Biol. 2020. Vol. 66, N 8. P. 41–46. |
| [41] |
Kachanov DA, Lakeenkov NM, Levitin KE, et al. Danio rerio (Zebrafish) – an universal model object in preclinical research. Forcipe. 2018;1(1):49–54. EDN: ZZAPGP |
| [42] |
Качанов Д.А., Лакеенков Н.М., Левикин К.Е., и др. Danio rerio (Zebrafish) как универсальный модельный объект в доклинических исследованиях // Forcipe. 2018. Т. 1, № 1. С. 49–54. EDN: ZZAPGP |
| [43] |
Clelland E, Peng C. Endocrine/paracrine control of zebrafish ovarian development. Mol Cell Endocrinol. 2009;312(1–2):42–52. doi: 10.1016/j.mce.2009.04.009 |
| [44] |
Clelland E., Peng C. Endocrine/paracrine control of zebrafish ovarian development // Mol Cell Endocrinol. 2009. Vol. 312, N 1–2. P. 42–52. doi: 10.1016/j.mce.2009.04.009 |
| [45] |
Yesudhason BV, Selvan Christyraj JRS, Ganesan M, et al. Developmental stages of zebrafish (Danio rerio) embryos and toxicological studies using foldscope microscope. Cell Biol Intern. 2020;44(10):1968–1980. doi: 10.1002/cbin.11412 |
| [46] |
Yesudhason B.V., Selvan Christyraj J.R.S., Ganesan M., et al. Developmental stages of zebrafish (Danio rerio) embryos and toxicological studies using foldscope microscope // Cell Biol Int. 2020. Vol. 44, N 10. P. 1968–1980. doi: 10.1002/cbin.11412 |
| [47] |
Kettleborough RN, Busch-Nentwich EM, Harvey SA, et al. A systematic genome-wide analysis of zebrafish protein-coding gene function. Nature. 2013;496(7446):494–497. doi: 10.1038/nature11992 |
| [48] |
Kettleborough R.N., Busch-Nentwich E.M., Harvey S.A., et al. A systematic genome-wide analysis of zebrafish protein-coding gene function // Nature. 2013. Vol. 496, N 7446. P. 494–497. doi: 10.1038/nature11992 |
| [49] |
Varga M, Ralbovszki D, Balogh E, et al. Zebrafish models of rare hereditary pediatric diseases. Diseases. 2018;6(2):43. doi: 10.3390/diseases6020043 |
| [50] |
Varga M., Ralbovszki D., Balogh E., et al. Zebrafish models of rare hereditary pediatric diseases // Diseases. 2018. Vol. 6, N 2. P. 43. doi: 10.3390/diseases6020043 |
| [51] |
Liu C, Li R, Li Y, et al. Spatiotemporal mapping of gene expression landscapes and developmental trajectories during zebrafish embryogenesis. Dev Cell. 2022;57(10):1284–1298.e5. doi: 10.1016/j.devcel.2022.04.009 |
| [52] |
Liu C., Li R., Li Y., et al. Spatiotemporal mapping of gene expression landscapes and developmental trajectories during zebrafish embryogenesis // Dev Cell. 2022. Vol. 57, N 10. P. 1284–1298.e5. doi: 10.1016/j.devcel.2022.04.009 |
| [53] |
Aanes H, Collas P, Aleström P. Transcriptome dynamics and diversity in the early zebrafish embryo. Brief Funct Genomics. 2014;13(2):95–105. doi: 10.1093/bfgp/elt049 |
| [54] |
Aanes H., Collas P., Aleström P. Transcriptome dynamics and diversity in the early zebrafish embryo // Brief Funct Genomics. 2014. Vol. 13, N 2. P. 95–105. doi: 10.1093/bfgp/elt049 |
| [55] |
Rauwerda H, Pagano JF, de Leeuw WC, et al. Transcriptome dynamics in early zebrafish embryogenesis determined by high-resolution time course analysis of 180 successive, individual zebrafish embryos. BMC Genomics. 2017;18(1):287. doi: 10.1186/s12864-017-3672-z |
| [56] |
Rauwerda H., Pagano J.F., de Leeuw W.C., et al. Transcriptome dynamics in early zebrafish embryogenesis determined by high-resolution time course analysis of 180 successive, individual zebrafish embryos // BMC Genomics. 2017. Vol. 18, N 2. P. 287. doi: 10.1186/s12864-017-3672-z |
| [57] |
Williams TD, Mirbahai L, Chipman JK. The toxicological application of transcriptomics and epigenomics in zebrafish and other teleosts. Brief Funct Genomics. 2014;13(2):157–171. doi: 10.1093/bfgp/elt053 |
| [58] |
Williams T.D., Mirbahai L., Chipman J.K. The toxicological application of transcriptomics and epigenomics in zebrafish and other teleosts // Brief Funct Genomics. 2014. Vol. 13, N 2. P. 157–171. doi: 10.1093/bfgp/elt053 |
| [59] |
Hill AJ, Teraoka H, Heideman W, et al. Zebrafish as a model vertebrate for investigating chemical toxicity. Toxicol Sci. 2005;86(1):6–19. doi: 10.1093/toxsci/kfi110 |
| [60] |
Hill A.J., Teraoka H., Heideman W., et al. Zebrafish as a model vertebrate for investigating chemical toxicity // Toxicol Sci. 2005. Vol. 86, N 1. P. 6–19. doi: 10.1093/toxsci/kfi110 |
| [61] |
Parhar IS, Ogawa S, Sakuma Y. Laser-captured single digoxigenin-labeled neurons of gonadotropin-releasing hormone types reveal a novel G protein-coupled receptor (Gpr54) during maturation in cichlid fish. Endocrinology. 2004;145(8):3613–3618. doi: 10.1210/en.2004-0395 |
| [62] |
Parhar I.S., Ogawa S., Sakuma Y. Laser-captured single digoxigenin-labeled neurons of gonadotropin-releasing hormone types reveal a novel G protein-coupled receptor (Gpr54) during maturation in cichlid fish // Endocrinology. 2004. Vol. 145, N 8. P. 3613–3618. doi: 10.1210/en.2004-0395 |
| [63] |
Ohga H, Adachi H, Kitano H, et al. Kiss1 hexadecapeptide directly regulates gonadotropin-releasing hormone 1 in the scombroid fish, chub mackerel. Biol Reprod. 2017;96(2):376–388. doi: 10.1095/biolreprod.116.142083 |
| [64] |
Ohga H., Adachi H., Kitano H., et al. Kiss1 hexadecapeptide directly regulates gonadotropin-releasing hormone 1 in the scombroid fish, chub mackerel // Biol Reprod. 2017. Vol. 96, N 2. P. 376–388. doi: 10.1095/biolreprod.116.142083 |
| [65] |
Li S, Zhang Y, Liu Y, et al. Structural and functional multiplicity of the kisspeptin/GPR54 system in goldfish (Carassius auratus). J Endocrinol. 2009;201(3):407–418. doi: 10.1677/JOE-09-0016 |
| [66] |
Li S., Zhang Y., Liu Y., et al. Structural and functional multiplicity of the kisspeptin/GPR54 system in goldfish (Carassius auratus) // J Endocrinol. 2009. Vol. 201, N 3. Р. 407–418. doi: 10.1677/JOE-09-0016 |
| [67] |
Selvaraj S, Ohga H, Kitano H, et al. Peripheral administration of kiss1 pentadecapeptide induces gonadal development in sexually immature adult scombroid fish. Zool Sci. 2013;30(6):446–454. doi: 10.2108/zsj.30.446 |
| [68] |
Selvaraj S., Ohga H., Kitano H., et al. Peripheral administration of kiss1 pentadecapeptide induces gonadal development in sexually immature adult scombroid fish // Zool Sci. 2013. Vol. 30, N 6. P. 446–454. doi: 10.2108/zsj.30.446 |
| [69] |
Ohga H, Selvaraj S, Adachi H, et al. Functional analysis of kisspeptin peptides in adult immature chub mackerel (Scomber japonicus) using an intracerebroventricular administration method. Neurosci Lett. 2014;561:204–207. doi: 10.1016/j.neulet.2013.12.072 |
| [70] |
Ohga H., Selvaraj S., Adachi H., et al. Functional analysis of kisspeptin peptides in adult immature chub mackerel (Scomber japonicus) using an intracerebroventricular administration method // Neurosci Lett. 2014. Vol. 561. P. 204–207. doi: 10.1016/j.neulet.2013.12.072 |
| [71] |
Kanunnikova NP. Neuroprotective properties of neuropeptides. Journal of the Grodno State Medical University. 2018;15(5):492–498. EDN: YKYYJW doi: 10.25298/2221-8785-2017-15-5-492-498 |
| [72] |
Канунникова Н.П. Нейропротекторные свойства нейропептидов // Журнал Гродненского государственного медицинского университета. 2018. Т. 15, № 5. С. 492–498. EDN: YKYYJW doi: 10.25298/2221-8785-2017-15-5-492-498 |
| [73] |
Taghizadeh V, Imanpoor MR, Mehdinejad N. Study the seasonal steroid hormones of common carp in Caspian Sea, Iran. Springerplus. 2013;2(1):193. doi: 10.1186/2193-1801-2-193 |
| [74] |
Taghizadeh V., Imanpoor M.R., Mehdinejad N., et al. Study the seasonal steroid hormones of common carp in Caspian Sea, Iran // Springerplus. 2013. Vol. 2, N 1. P. 193. doi: 10.1186/2193-1801-2-193 |
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