Abstract
BackgroundRecent evidence from rodent ovaries has demonstrated expression of fractalkine and the existence of fractalkine receptor, and showed that there is a significant increase in steroidogenesis in response to fractalkine, yet the role of fractalkine and CX3CR1 in the human ovary is still unknown. This study aimed to determine the expression levels of fractalkine and CX3CR1 in the human ovary and to investigate their roles in sexual hormone biosynthesis by human luteinising granulosa cells. This is the first detailed report of fractalkine and CX3CR1 expression and function in the human ovary.MethodsFractalkine and CX3CR1 expression levels were measured by immunohistochemistry using ovarian tissue from pathological specimens from five individuals. Granulosa cells were obtained from patients during IVF treatment. They were cultured and treated with increasing doses of hCG with or without fractalkine. Media were collected to detect estradiol and progesterone by chemiluminescence. StAR, 3-βHSD and CYP11A expression were determined in granulosa cells treated with or without fractalkine by real-time RT-PCR.ResultsFractalkine and CX3CR1 were expressed in the human ovary and in luteinising granulosa cells. However, fractalkine expression was stronger in luteinising granulosa cells. Treatment with fractalkine augmented hCG stimulation of progesterone production in a dose-dependent manner with concomitant increases in transcript levels for key steroidogenic enzymes (StAR, 3-βHSD and CYP11A) but had no effect on estradiol biosynthesis(P < 0.05).ConclusionsFractalkine and CX3CR1 were found to express in human ovary and luteinising granulosa cells. Fractalkine can increase the biosynthesis of progesterone in a dose-dependent manner by enhancing transcript levels of key steroidogenic enzymes.
Highlights
Recent evidence from rodent ovaries has demonstrated expression of fractalkine and the existence of fractalkine receptor, and showed that there is a significant increase in steroidogenesis in response to fractalkine, yet the role of fractalkine and CX3CR1 in the human ovary is still unknown
Expression of fractalkine and its receptor CX3CR1 in the human ovary Immunohistochemical analysis from pathological specimens from 5 individuals demonstrated that fractalkine was expressed in granulosa cells in the follicular phase in human ovaries
Location of fractalkine and CX3CR1 in human luteinised granulosa cells Observation using a confocal laser scanning microscope showed that fractalkine was distributed in the cytoplasm of human luteinised granulosa cells, and CX3CR1 was expressed in the membranes of human luteinised granulosa cells (Figure 2)
Summary
Recent evidence from rodent ovaries has demonstrated expression of fractalkine and the existence of fractalkine receptor, and showed that there is a significant increase in steroidogenesis in response to fractalkine, yet the role of fractalkine and CX3CR1 in the human ovary is still unknown. This study aimed to determine the expression levels of fractalkine and CX3CR1 in the human ovary and to investigate their roles in sexual hormone biosynthesis by human luteinising granulosa cells. This is the first detailed report of fractalkine and CX3CR1 expression and function in the human ovary. Previous studies have demonstrated the importance of multiple intraovarian ligand-receptor signalling systems in modulating ovarian function. These factors play paracrine and/or autocrine role(s) in oocyte maturation, ovulation, and luteinisation [1,2]. Recombinant fractalkine was found to activate a seven transmembrane receptor CX3CR1 [6]
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