Kisspeptin regulates ovarian steroidogenesis during delayed embryonic development in the fruit bat, Cynopterus sphinx

Abstract

Cynopterus sphinx, a fruit bat, undergoes delayed embryonic development during the winter months, a period that corresponds to low levels of progesterone and estradiol synthesis by the ovary. Kisspeptins (KPs) are a group of neuropeptide hormones that act via G-protein coupled receptor 54 (GPR54) to stimulate hypothalamic secretion of Gonadotropin-releasing hormone, thereby regulating ovarian steroidogenesis, folliculogenesis, and ovulation. GPR54 is also expressed in the ovary, suggesting a direct role for KPs in ovarian steroidogenesis. The aim of present study was to determine if a low serum level of KP is responsible for reduced progesterone and estradiol levels during the period of delayed embryonic development in C. sphinx. Indeed, low serum KP abundance corresponded to reduced expression of GPR54 in ovarian luteal cells during the period of delayed development compared to normal development. In vitro and in vivo treatment with KP increased GPR54 abundance, via Extracellular signal regulated kinase and its downstream mediators, leading to increased progesterone synthesis in the ovary during delayed embryonic development. KP treatment also increased cholesterol uptake and elevated expression of Luteinizing hormone receptor and Steroid acute regulatory protein in the ovary, suggesting that elevation in circulating KP during delayed embryonic development may reactivate luteal activity. KPs may also enhance cell survival (BCL-2, reduced Caspase 3 activity) and angiogenesis (Vascular endothelium growth factor) during this period. The findings of this study thus demonstrate a regulatory role for KPs in the maintenance of luteal steroidogenesis during pregnancy in C. sphinx.

Kisspeptin-10 Promotes Progesterone Synthesis in Bovine Ovarian Granulosa Cells via Downregulation of microRNA-1246

“…The expression of kisspeptin and KISS1R in buffalo ovary is affected by the follicles, and the expression is higher in the GCs of the follicles with high P4 concentration [ 16 ], indicating the potential relationship between kisspeptin and P4 synthesis. Previous studies suggest that kisspeptin could stimulate P4 synthesis in porcine, chicken, rat, and bat ovarian GCs [ 17 , 18 , 19 , 20 ]. However, the effect and mechanism of kp-10 on P4 synthesis in bovine ovarian GCs (BGCs) is still unclear.…”

Gametogenic and steroidogenic action of kisspeptin-10 in the Asian catfish, Clarias batrachus: Putative underlying mechanistic cascade

“…Similarly, levels of StAR, CYP11a and 3β-HSD transcripts were also increased by KP-10 in the rat luteal cells (Peng et al, 2013). Recently, Anuradha and Krishna (2017) have also reported increased expressions of StAR and 3β-HSD in response to KP-10 in bat ovarian explants. Thus, these few studies in mammalian species support our notion of KP-10-stimulated gonadal steroidogenesis.…”

“…However, non-availability of such studies makes us difficult to correlate and discuss the present findings. Nevertheless, few studies on mammalian species are available (Anuradha and Krishna, 2017;Peng et al, 2013;Xiao et al, 2011). Xiao et al (2011) have shown that mammalian kisspeptin-10 up-regulates the expressions of, P450scc and StAR in cultured chicken granulosa cells.…”

Kisspeptin promotes follicular development through its effects on modulation of P450 aromatase expression and steroidogenesis in sheep ovarian follicles

“…The production of higher levels of E 2 in the kisspeptin supplemented groups in our study goes parallel with Sirotkin (2014), in which they reported that the support provided by kisspeptin towards the developing follicles in proliferation and further growth was by stimulating granulosa cells to secrete Estradiol‐17β during culture. Nonsignificant increase in the concentration of E 2 during culture (Group I; Table 1) is in line with earlier observation in fruit bat luteal cells cultured in lower concentrations of kisspeptin (Anuradha and Krishna A., 2017). In contrast Peng et al (2013) reported the production of progesterone but not Estradiol‐17β in the cultured luteal cells indicating the possibility of E 2 secretion and its regulation was an indirect action of KP through hypothalamic neuronal networks controlling GnRH secretion (Castellano et al, 2010).…”