Kisspeptin: Applications in Reproductive Health and Enhancement of Fertility Functions

By Cocer Peptides      1 month ago

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1. Overview

Kisspeptin is a neuropeptide encoded by the Kiss1 gene, primarily expressed in the arcuate nucleus and preoptic area of the hypothalamus. It plays a key role in regulating reproductive function and serves as an important upstream regulator of the hypothalamic-pituitary-gonadal (HPG) axis. Kisspeptin binds to the G protein-coupled receptor 54 (GPR54), activating a series of signaling pathways to regulate reproductive function. One of the hallmarks of puberty onset is the pulsatile secretion of gonadotropin-releasing hormone (GnRH) by hypothalamic GnRH neurons, and kisspeptin serves as a critical upstream regulatory component of GnRH neurons, playing a key role in the maturation of the reproductive axis.

Figure 1 Cellular action mechanism of kisspeptin.

2. Function

Regulation of puberty onset: In mammals, the expression of kisspeptin and its receptor GPR54 significantly increases before the onset of puberty. It activates GnRH neurons, promoting pulsatile GnRH release and thereby initiating puberty. In humans and other mammals, the absence of kisspeptin signaling leads to hypogonadism due to insufficient gonadotropin secretion, thereby impairing the normal onset of puberty.

Regulation of reproductive hormone secretion: Kisspeptin stimulates the anterior pituitary gland to secrete gonadotropins, including follicle-stimulating hormone (FSH) and luteinizing hormone (LH). This is achieved by increasing GnRH secretion, which in turn stimulates anterior pituitary cells to synthesize and release FSH and LH, thereby regulating gonadal function, promoting the synthesis of gonadal steroid hormones, and facilitating the development of germ cells.

Influencing the reproductive cycle: In female animals, kisspeptin participates in regulating the menstrual cycle or estrous cycle. During the menstrual cycle, kisspeptin neurons are highly sensitive to feedback regulation by estrogen. When estrogen levels rise, kisspeptin neuron activity increases, further promoting GnRH release, triggering an LH surge, and inducing ovulation. In seasonally breeding animals such as sheep, the expression and activity of Kisspeptin neurons change with seasonal variations, affecting GnRH secretion and thereby regulating the breeding season.

Participation in reproductive-related physiological processes: Kisspeptin not only directly influences the gonadal axis but also participates in other reproductive-related physiological processes. In the ovaries, the expression of Kisspeptin and its receptors is closely associated with follicle development, maturation, and ovulation. It influences follicle growth and steroid hormone synthesis by regulating local endocrine and paracrine signals in the ovaries. In the testes, Kisspeptin may also participate in the regulation of spermatogenesis and testosterone secretion.  

3. Applications

Treatment of female infertility: In the treatment of female infertility, Kisspeptin has demonstrated potential application value. For patients with ovulatory abnormalities or insufficient gonadotropin secretion due to hypothalamic-pituitary dysfunction, exogenous administration of Kisspeptin or its analogues may restore normal ovulatory function by stimulating GnRH and gonadotropin secretion. For example, in some clinical studies, treatment with Kisspeptin analogues in patients with functional hypothalamic amenorrhea was found to induce increased secretion of LH and FSH, with some patients regaining ovulation and menstrual cycles.

Improving male reproductive function: In the field of male reproductive health, Kisspeptin also holds promising applications. For male patients with oligoasthenozoospermia or hypogonadism caused by insufficient gonadotropin secretion, Kisspeptin therapy may improve sperm quality and quantity by promoting the release of GnRH and gonadotropins, thereby increasing testosterone secretion. Animal studies have shown that administration of Kisspeptin can increase testosterone levels in male animals, promote spermatogenesis, and enhance reproductive capacity.

Assisted reproductive technology: In the in vitro fertilization-embryo transfer (IVF-ET) process, precise control of female ovulation and hormone levels is critical. Kisspeptin can serve as a new drug target for optimizing ovulation induction protocols. By regulating the Kisspeptin signaling pathway, it may be possible to more precisely control follicle development and ovulation, improve egg retrieval rates and embryo quality, thereby enhancing the success rate of IVF-ET.

4. Conclusion

In summary, Kisspeptin offers new approaches for enhancing reproductive function in human fertility treatment.

Sources

[1] Szeliga A, Męczekalski B. Kisspeptin Modulation of Reproductive Function[J]. Endocrines, 2022. https://api.semanticscholar.org/CorpusID:250228276.

[2] Rt A K U K, Kuru M, Başer O M, et al. Kisspeptin: Role in Female Infertility[J]. Reproductive Hormones, 2020. https://api.semanticscholar.org/CorpusID:229493075.

[3] Smith J T, Hawken P A R, Lehman M N, et al. The role of kisspeptin in reproductive function in the ewe[J]. Bioscientifica Proceedings, 2019. https://api.semanticscholar.org/CorpusID:85961626.

[4] Clarke H, Dhillo W S, Jayasena C N. Comprehensive Review on Kisspeptin and Its Role in Reproductive Disorders[J]. Endocrinology and Metabolism, 2015,30(2):124-141.DOI:10.3803/EnM.2015.30.2.124.

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