Regulation of kisspeptin and gonadotropin-releasing hormone expression in rat placenta: study using primary cultures of rat placental cells

Abstract

BackgroundGonadotropin-releasing hormone (GnRH) and kisspeptin in the hypothalamus are thought to be crucial components of the hypothalamic-pituitary-gonadal (HPG) axis and maintain reproductive function. These neuropeptides are also expressed in the placenta, where they may contribute to placental physiology. In this study, we examined how these peptides are regulated within the placenta.MethodsWe used primary cultures of placental tissue from rats of 16–18 days gestation. After stimulation with estradiol, GnRH, kisspeptin, and neurokinin B (NKB), changes in placental GnRH, kisspeptin, and human chorionic gonadotropin (hCG) mRNA expression were evaluated by real-time quantitative RT-PCR analysis.ResultsImmunocytochemical analysis showed that rat placental cells contained cells expressing kisspeptin or GnRH. GnRH and kisspeptin mRNA expression was significantly increased in placental cells in the presence of estradiol; NKB mRNA expression was also stimulated by estradiol. Stimulation of the cells with kisspeptin failed to stimulate GnRH mRNA expression. Conversely, both GnRH itself and NKB increased GnRH mRNA expression. Kisspeptin mRNA expression was not increased by kisspeptin itself; however, GnRH and NKB significantly increased kisspeptin mRNA expression. hCG expression was increased in the presence of estradiol. In addition, kisspeptin, GnRH, and NKB could stimulate the expression of hCG mRNA in placental cells.ConclusionsOur experiments using primary cultures of rat placental cells showed that GnRH, kisspeptin, and NKB expression was enhanced by estradiol, and unlike in the hypothalamus, kisspeptin did not control the expression of GnRH in placental cells. NKB might be located upstream of kisspeptin and GnRH, and these neuropeptides might be involved in the induction of hCG expression in placental cells.

Maternal plasma kisspeptin‐10 level in preeclamptic pregnant women and its relation in changing their reproductive hormones

“…However, a positive correlation between KP‐10 and β‐hCG was noticed during the 3rd trimester in PE women. A finding that was also noticed by other researchers Oride et al . who reported the stimulatory effect of kisspeptin on hCG mRNA expression in rat placental cells.…”

“…High concentrations of KP‐10 have been observed to correlate with sex steroids, which suggests KP‐10 is released during pregnancy and related to the placental size. Likewise, expression of KP‐10 mRNA has been observed to be augmented in both human and rat placenta . High concentrations of KP‐10 have been found in syncytiotrophoblasts, which secrete several hormones.…”

“…High concentrations of KP‐10 have been found in syncytiotrophoblasts, which secrete several hormones. This includes, human chorionic gonadotropin (hCG), placental growth hormone, estrogen (E2) and progesterone (PRG) . The effect of KP‐10 on luteinizing hormone (LH) surge, gonadotropin‐releasing hormone and follicle stimulating hormone (FSH) secretion has been demonstrated in humans as well as in animal models …”

Kisspeptin‐10 and the G protein‐coupled receptor 54 are differentially expressed in the canine pregnant uterus and trophoblast cells

“…Regulation of KP and GPR54 expressions in the uterus and placenta is unclear. In cultured rat trophoblasts, GnRH increases KP‐10 expression, which is just the opposite effect in the hypothalamus (Oride et al., ). GnRH and its receptor are expressed in canine trophoblast cells and are upregulated at uteroplacental sites (Schäfer‐Somi et al., ).…”

Kisspeptin and Glucose Homeostasis

“…53,54 The extent of placental kisspeptin release in animal models is unclear due to the lack of reliable assays; however, kisspeptin mRNA is expressed and increases through pregnancy in rodent and dog placenta, supporting placental kisspeptin release in other animals. [55][56][57] Thus, pregnancy represents a physiological state in which the islets are exposed to kisspeptin at elevated levels, which may be stimulatory.…”