• Journal of Animal Reproduction and Biotechnology
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• v.36 no.1
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• pp.51-58
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• 2021

Kisspeptin, a neuropeptide and the master controller of reproductive axis upstream to GnRH neurons, and its receptor are also expressed in extra-hypothalamic tissues, such as ovaries. As systemic kisspeptin has been shown to modulate follicular dynamics in cattle, we hypothesized that kisspeptin has direct actions on the ovarian follicular development. We also hypothesized that kisspeptin regulation of primordial follicle development is via modulation of VEGF expression. In order to test these hypotheses, we cultured caprine ovarian cortical strips in vitro for 7 days with supplementation of kisspeptin at 1, 10 and 100 µM concentration and observed the development of primordial follicles into intermediate, primary and secondary follicles. We also studied the alteration in the expression profile of VEGF and VEGF transcript variant 2 mRNA during follicular development in the presence of kisspeptin. We confirmed the presence of GPR54 in goat ovaries in our preliminary studies. Supplementation of kisspeptin at 1 and 10 µM concentration facilitated the development of primordial follicles into intermediate, primary and secondary follicles with less number of degenerated follicles while the same at 100 µM resulted in degeneration of follicles. We observed a drastic increase in the expression profile of VEGF and VEGF transcript variant 2 mRNA upon culture which was independent of kisspeptin treatment. In conclusion, our studies show that kisspeptin facilitates ovarian primordial development in vitro.

• Asian-Australasian Journal of Animal Sciences
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• v.25 no.6
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• pp.785-788
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• 2012

The aim of the present study was to clarify the effect of kisspeptin-10 on LH secretion in prepubertal ewes. In experiment 1, prepubertal ewes fitted with indwelling jugular catheters were randomly assigned to receive 0, 0.5, 1 or 2 mg of kisspeptin-10 dissolved in saline, and serial blood samples were collected at 15-min intervals for 180 min to analyze the response curves of LH after injection. In experiment 2, prepubertal ewes fitted with indwelling jugular catheters were injected with 0 or 1 mg of kisspeptin-10 dissolved in saline and the injection was repeated 3 times at 1 h interval and serial blood samples were collected at 15-min intervals for 210 min to analyze the response curves of LH after injection. The results showed that single intravenous administration of 0.5, 1 and 2 mg of kisspeptin-10 all could significantly increased LH secretion in prepubertal ewes, and the effect of 1 and 2 mg of kisspeptin-10 on LH secretion was higher than that of 0.5 mg group. The results also showed that repeated intravenous administration of kisspeptin-10 could effectively increase LH secretion and repeated administration did not influence the effect of kisspeptin-10 on LH secretion in prepubertal ewe. In conclusion, the present study indicated that single or repeated intravenous administration of kisspeptin-10 could effectively increase LH secretion in prepubertal ewes.

• Development and Reproduction
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• v.26 no.3
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• pp.107-115
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• 2022

Kisspeptins, products of KISS1 gene, are ligands of the G-protein coupled receptor (GPR54), and the kisspeptin-GPR54 signaling has an important role as an upstream regulator of gonadotropin releasing hormone (GnRH) neurons. Interestingly, extrahypothalamic expressions of kisspeptin/GPR-54 in gonads have been found in primates and experimental rodents such as rats and mice. Hamsters, another potent experimental rodent, also have a kisspeptin-GPR54 system in their ovaries. The presence of testicular kisspeptin-GPR54 system, however, remains to be solved. The present study was undertaken to determine whether the kisspeptin is expressed in hamster testis. To do this, reverse transcription-polymerase chain reactions (RT-PCRs) and immunohistochemistry (IHC) were employed. After the nest PCR, two cDNA products (320 and 280 bp, respectively) were detected by 3% agarose gel electrophoresis, and sequencing analysis revealed that the 320 bp product was correctly amplified from hamster kisspeptin cDNA. Modest immunoreactive (IR) kisspeptins were detected in Leydig-interstitial cells, and the weak signals were detected in germ cells, mostly in round spermatids and residual bodies of elongated spermatids. In the present study, we found the kisspeptin expression in the testis of Syrian hamster. Further studies on the local role(s) of testicular kisspeptin are expected for a better understanding the physiology of hamster testis, including photoperiodic gonadal regression specifically occurred in hamster gonads.

• Journal of Animal Reproduction and Biotechnology
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• v.36 no.1
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• pp.25-34
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• 2021

Kisspeptin is a key player in the central control of reproductive axis. Central administration of kisspeptin has been shown to advance puberty in rats. Stimulation of hypothalamic GnRH pulse generating mechanism by kisspeptin has been proposed to be the mechanism behind the onset of puberty. We hypothesized that chronic high doses of kisspeptin administration suppresses the reproductive axis and hence delays the pubertal onset. Hence, we investigated the effect of peripheral administration of chronic high doses of kisspeptin on pubertal onset, feed intake and body weight in female rats. Rats were treated with saline or kisspeptin (100 nmoles per day; intraperitoneal) for 26 days (day 25 to day 50 postnatal) and the day of vaginal opening was marked as day of puberty. Kisspeptin treated rats had delayed pubertal onset and reduced feed intake and body weight. Gonadal GPR54 mRNA was reduced suggesting that chronic high doses of kisspeptin may suppress the reproductive functions possibly by downregulation of GPR54 receptor. However, delay in puberty due to reduction in feed intake and body weight could not be ruled out in this study. Further, our study emphasizes the importance of dosage and duration of kisspeptin administration in the manipulation of reproductive axis. Our study, for the first time, suggests that kisspeptin and its analogues, if proven beneficial, could be used to treat precocious puberty in children. It appears that, though a promising tool for enhancing fertility, kisspeptin acts as a double-edged sword and has to be cautiously used to manipulate reproduction.

• Journal of Animal Reproduction and Biotechnology
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• v.34 no.1
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• pp.40-49
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• 2019

Chronic and unpredictable stress can disrupt the female reproductive system by suppression for secretion of gonadotrophin-releasing hormone (GnRH) and gonadotrophin, resulted in ovarian malfunction and infertility. In the recent days, kisspeptin has been highly highlighted as a hypothalamic peptide which directly stimulates synthesis and release for GnRH. However, in spite of the key role of kisspeptin in the female reproductive system, little information is still available on the changes of its expression during ovarian cycle under stressed condition. Therefore, we induced chronic and unpredictable stress series to the female mice to analyze kisspeptin expression in the brain and ovary. Stressed mice exhibited changes of behavior and body weight gain during the stress assessment, which suggested that the present stress model in mice was successfully established. In the brain level, kisspeptin expression was attenuated than control. In the ovary level, the stressed mice displayed irregularly shrunk oocytes with broken zona pellucida throughout the follicle stages, pyknotic granulosa cells, decreased number of developing follicles and increased number of atretic follicles than the control. In case of kisspeptin expression in the whole ovary tissue, the expression level was decreased in the stressed mice. In detail, the less intensity of kisspeptin expression in the antral follicles phase was observed in the stressed mice than control mice, indicating that local function of kisspeptin during ovary cycle is highly associated with development of ovarian follicles. We expect that the present study has important implications for the fields of reproductive biology.

• Journal of Integrative Natural Science
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• v.11 no.1
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• pp.9-13
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• 2018

KiSS1-derived peptide receptor, a GPCR protein, binds with the hormone Kisspeptin plays a major role in the neuroendocrine regulation of reproduction. It is important in the onset of puberty and triggers the release of gonadotrophin-releasing hormone. It is a potential drug target for the disorders related to GnRH, hence, analysing the structural features of the receptor becomes important. The three dimensional of the receptor modelled in a previous study was utilised. In this study, we have analysed the protein - protein interaction of the receptor with Kisspeptin 10 and 15. The study revealed the important residues which are involved in the interaction. The result of this study could be helpful in understanding the mechanism of Kiss1 receptor activation and the pathophysiology of the disorders related to the receptor.

• Development and Reproduction
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• v.24 no.3
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• pp.149-158
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• 2020

Kisspeptin, expressed mainly in the hypothalamus, stimulates gonadotropin-releasing hormone neurons to facilitate reproduction. In some model animals, the kisspeptin is also expressed in the pituitary. Recently, a pathway has been suggested in which kisspeptin acts directly on the pituitary to secretion of gonadotropin in mammals. In the present study, pituitaries of the Nile tilapia (Oreochromis niloticus) were cultured at different concentrations of kisspeptin-10 (Kp-10, FNYNPLSLRF) for 3 hours to observe the effect of kisspeptin on the expression of follicle-stimulating hormone β subunit (fshβ) gene and luteinizing hormone β subunit (lhβ) gene. Pituitary tissues were cultured with 0.1 μM of Kp-10, luteinizing hormone releasing hormone (LHRH), or LHRH+Kp-10 for 3, 6, 12, and 24 hours to investigate changes in the expression of fshβ and lhβ mRNA. Pituitaries cultured with high concentration of Kp-10 more than 0.1 μM for 3 hours exhibited a significant increase of fshβ mRNA expression, but not lhβ mRNA. The expression of both fshβ and lhβ mRNA increased after 6 hours in 0.1 μM of Kp-10 medium in comparison with that in the control medium. Tissues cultured in the LHRH medium however exhibited increased expression of both genes not only at 6 but also 12 hours. There were no significant differences of fshβ and lhβ gene expression in tissues cultured with LHRH+KP-10 medium compared with the control. These results suggested that although kisspeptin plays an important role in fshβ and lhβ expression in the pituitary of Nile tilapia, its action is far more complicated than expected.

• Molecules and Cells
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• v.43 no.7
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• pp.600-606
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• 2020

Numerous physiological processes in nature have multiple oscillations within 24 h, that is, ultradian rhythms. Compared to the circadian rhythm, which has a period of approximately one day, these short oscillations range from seconds to hours, and the mechanisms underlying ultradian rhythms remain largely unknown. This review aims to explore and emphasize the implications of ultradian rhythms and their underlying regulations. Reproduction and developmental processes show ultradian rhythms, and these physiological systems can be regulated by short biological rhythms. Specifically, we recently uncovered synchronized calcium oscillations in the organotypic culture of hypothalamic arcuate nucleus (ARN) kisspeptin neurons that regulate reproduction. Synchronized calcium oscillations were dependent on voltage-gated ion channel-mediated action potentials and were repressed by chemogenetic inhibition, suggesting that the network within the ARN and between the kisspeptin population mediates the oscillation. This minireview describes that ultradian rhythms are a general theme that underlies biological features, with special reference to calcium oscillations in the hypothalamic ARN from a developmental perspective. We expect that more attention to these oscillations might provide insight into physiological or developmental mechanisms, since many oscillatory features in nature still remain to be explored.

• Journal of Marine Life Science
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• v.1 no.1
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• pp.41-49
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• 2016

Kisspeptin (Kiss) and its cognate receptor, kisspeptin receptor (KissR; G protein coupled receptor 54, GPR54), have recently been recognized as potent regulators of reproduction in teleosts. Additionally, leptin plays an important role in energy homeostasis and reproductive function in teleosts. The purpose of this study was to examine differences in the concentration of the hormones of the Kiss/KissR system and leptin and the expression of their underlying genes, all of which are involved in the sexual maturation of female goldfish, Carassius auratus, following treatment with Kiss. The expression levels of KissR increased after the Kiss injection. Furthermore, the peptide hormone leptin also increased after the injection (in vivo and in vitro). Additionally, the expression of GnRH and GTHs (GTHα, FSHβ, and LHβ) increased in the brain and pituitary (in vitro and in vitro). These results support the hypothesis that Kiss plays important roles in the direct regulation of the hypothalamus-pituitary-gonad axis and leptin in goldfish. Therefore, we suggest that Kiss system gene expression is correlated with energy balance and reproduction.

• Asian-Australasian Journal of Animal Sciences
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• v.25 no.9
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• pp.1229-1236
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• 2012

Our previous studies showed that kisspeptin-10 (Kp-10) injected in vivo can markedly increase lipid anabolism in liver of quails. In order to investigate the direct effect of Kp-10 on lipid metabolism of hepatocytes in birds, cells were separated from embryos livers and cultured in vitro with 0, 100 and 1,000 nM Kp-10, respectively. The results showed that after 24 h treatment, cells viability was not affected by 100 nM Kp-10, but showed a mild decrease with 1,000 nM Kp-10 compared to the control cells. Based on the results of the cell viability, 100 nM dosage of Kp-10 was selected for the further study and analysis. Compared with control cells, total cholesterol (Tch) contents in 100 nM treated cells were increased by 51.23%, but did not reach statistical significance, while the level of triglyceride (TG), high density of lipoprotein-cholesterol (HDL-C) and low density of lipoprotein-cholesterol (LDL-C) were significantly increased. Real-time PCR results showed that ApoVLDL-II mRNA expression had a tendency to increase, genes including sterol regulatory element-binding protein-1 (SREBP-1), acetyl coenzyme A carboxylase ${\alpha}$ ($ACC{\alpha}$), carnitine palmitoyltransferase 1 (CPT1), 3-hydroxyl-3-methylglutaryl-coenzyme A reductases (HMGCR) and stearyl coenzyme A dehydrogenase-1 (SCD1) mRNA in hepatocytes were significantly down-regulated by 100 nM Kp-10. However, contrary to its gene expression, SREBP-1 protein expression was significantly up-regulated by 100 nM Kp-10. Some of the significant correlations in mRNA expression were found between genes encoding hepatic factors or enzymes involved in lipid metabolism in liver of birds. These results indicate that Kp-10 stimulates lipid synthesis directly in primary cultured hepatocytes of chickens.