Peripheral action of kisspeptin at reproductive tissues—role in ovarian function and embryo implantation and relevance to assisted reproductive technology in livestock: a review

Abstract

Kisspeptin (KISS1) is encoded by the KISS1 gene and was initially found to be a repressor of metastasis. Natural mutations in the KISS1 receptor gene (KISS1R) were subsequently shown be associated with idiopathic hypothalamic hypogonadism and impaired puberty. This led to interest in the role of KISS1 in reproduction. It was established that KISS1 had a fundamental role in the control of GnRH secretion. KISS1 neurons have receptors for leptin and estrogen receptor α (ERα) which places KISS1 at the gateway of metabolic (leptin) and gonadal (ERα) regulation of GnRH secretion. More recently, KISS1 has been shown to act at peripheral reproductive tissues. KISS1 and KISS1R genes are expressed in follicles (granulosa, theca, oocyte), trophoblast and uterus. KISS1 and KISS1R proteins are found in the same tissues. KISS1 appears to have autocrine and paracrine actions in follicle and oocyte maturation, trophoblast development, and implantation and placentation. In some studies, KISS1 was beneficial to in vitro oocyte maturation and blastocyst development. The next phase of KISS1 research will explore potential benefits on embryo survival and pregnancy. This will likely involve longer-term KISS1 treatments during proestrus, early embryo development, trophoblast attachment, and implantation and pregnancy. A deeper understanding of the direct action of KISS1 at reproductive tissues could help to achieve the next step change in embryo survival and improvement in the efficiency of assisted reproductive technology.

The ontogeny of kisspeptin receptor in the uterine contractions in rats: Its possible role in the quiescence of non-pregnant and pregnant uteri

“…The vital role of the endometrial layer in the control of uterine contractility was already demonstrated by the local production of different agents affecting smooth muscle function (Kothencz et al, 2018). A networking is already proved with kisspeptin neurons in the central nervous system (Arthur et al, 2008) and the reproductive organs (D'Occhio et al, 2020), but no data is available for the uterine smooth muscle in this respect.…”

Effects of time-restricted feeding and type of food on fertility competence in female mice

“…Kisspeptin neurons which are located in the hypothalamus as with GnRH neurons are recognized to orchestrate the hypothalamus-pituitary-gonadal (HPG) axis, a robust mechanism for the regulation of reproduction both in male and female mammals 46 – 48 . As the main regulatory clock, the SCN, is controlled by the light–dark cycle 12 , but the circadian rhythms of peripheral tissues deviate from the SCN cycle due to insulin/IGF1-mediated feeding and fasting cycles 17 , 18 , our analysis was focused on the displacement of circadian rhythms in peripheral tissues such as ovary.…”

Role of Kisspeptin on Hypothalamic-Pituitary-Gonadal Pathology and Its Effect on Reproduction

“…The nidation depends on the degree of trophoblast infiltration into the uterine extracellular matrix where kisspeptin combined with other proinflammatory cytokines, notably tumor necrosis factor-alpha, blocks invasion by stimulating apoptosis [ 5 ]. As a result, KISS1 plays a part in controlling the rate of syncytiotrophoblast cell invasion and angiogenesis, ensuring that early placentation occurs in a controlled and sequential manner [ 30 ]. Moreover, KISS1R and GPR54 are predominantly expressed in the trophoblast of the first-trimester placenta, where the invasive capacity is at its highest.…”

“…Moreover, KISS1R and GPR54 are predominantly expressed in the trophoblast of the first-trimester placenta, where the invasive capacity is at its highest. On the contrary, KISS1R and GPR54 are poorly expressed in the full-term gestation placenta [ 30 ]. We can deduce that KISS1 has a similar part in the inhibition of cell migration in both early pregnancy and tumor metastasis [ 30 ].…”

“…On the contrary, KISS1R and GPR54 are poorly expressed in the full-term gestation placenta [ 30 ]. We can deduce that KISS1 has a similar part in the inhibition of cell migration in both early pregnancy and tumor metastasis [ 30 ].…”