Defining the chemokine repertoire of the mouse female reproductive tract

Background: The mechanisms governing leukocyte recruitment to the femalereproductive tract (FRT) play a critical role in protection from infection,remodelling during the estrus cycle, pregnancy and post-partum remodelling.Chemokines are key factors in driving tissue-specifi c leukocyte homing,yet little is known about their expression in the FRT. In this study, we havecharacterised the chemokine profi le of distinct anatomical compartments ofthe mouse FRT at each estrus cycle stage.
Methods: Ovary, uterine horn, cervix and vagina were obtained from nonpregnantmice (n=20) during proestrus, estrus, metestrus and diestrus, andexpression of 34 chemokines and 11 chemokine receptors were analysed usingTaqman Low Density Arrays. Lung, skin, small intestine and colon were usedas control tissues. Gene expression differences between tissues, and betweenestrus cycle stage were assessed by the Kruskal-Wallis test, followed by theDunn’s Multiple Comparison Test. p<0.05 was accepted as signifi cant.Results: The uterine horn exhibited expression of the largest number ofchemokines, with CCL28 and XCL1 predominantly expressed. Uterine CCL28expression was 20-fold higher than the ovaries (p<0.05), 50-fold higher thanthe cervix (p<0.0001) and 14-fold higher than the vagina (p<0.05). XCL1expression was approximately 20-fold higher than the ovaries and cervix, and30-fold higher than the vagina (all p<0.0001). Estrus cycle stage had minimaleffects on chemokine expression, although CCL7 was reduced during estrusand metestrus in the ovary (p<0.0269), cervix (p<0.0216) and vagina (p<0.015),and CCR4 dropped during diestrus in the ovary (p<0.0212), uterine horn(p<0.0291) and vagina (p<0.0051). Analysis of leukocyte marker expression(F4/80, CD3, CD11c, CD19, CD56, MBP) suggests that the uterine horn isthe principal home of most leukocyte subsets within the FRT, while the vaginaexhibited low expression of CD56, a marker of NK cells.
Conclusion: This study provides a foundation for more detailed analyses ofthe role of chemokines in leukocyte traffi cking to the FRT, and will aid studiesaimed at defi ning FRT leukocyte function in female reproductive health.