Expression And Regulation Of Hoxa-10 And IL-11Rα In Canine Uterus

Blastocyst implantation is a key step for successful establishment of pregnancy during mammalian reproduction. Successful implantation is dependent upon the interaction between the blastocyst and the uterus. The most fundamental feature of this process is the synchronized development of the embryo to the blastocyst stage and differentiation of the uterus to the receptive state. The aim of this study was to investigate the differential expression of Hoxa10 and IL-11Rαin canine uterus during early pregnancy and estrus cycle,and its regulation under steroid treatment by in situ hybridization.Hoxa10, a homeobox gene, is necessary for endometrial receptivity to blastocyst implantation in human and mice. Mice with a targeted disruption of the Hoxa10 gene are infertile due to defective embryo implantation and decidualization. Throughout the menstrual cycle, HOXA10 expression increases dramatically in the midsecretory at the time of implantation in human endometrium. However, the expression and regulation of Hoxa10 in canine reproduction are still undefined. Hoxa10 mRNA was mainly localized in glandular epithelium and myometrium in canine uterus. There was a low level of Hoxa10 expression in the glandular epithelium on days 6, 12 and 17 of pregnancy. On day 20 of pregnancy when embryo implanted, Hoxa10 mRNA was highly expressed in the glandular epithelium immediately surrounding the embryo. The expression of Hoxa10 mRNA gradually declined from day 23 and reached a low level on day 28. In the myometrium, a low level of Hoxa10 mRNA signal was seen on days 6, 12 and 17 of pregnancy and reached a high level on day 20 of pregnancy. During the estrous cycle, there was no detectable Hoxa10 mRNA signal in canine uteri at anestrous stage. But at estrous stage, a high level of Hoxa10 mRNA signal was found in the glandular epithelium and a low level was found in the myometrium of canine uteri. Either estrogen or progesterone significantly induced the expression of Hoxa10 mRNA in the ovariectomized canine uterus. These results suggest that Hoxa10 expression is closely related to canine implantation and up-regulated by estrogen and progesterone.Interleukin -11(IL-11), a pleiotropic cytokine, belongs to the IL-6 family of cytokines. IL-11 brings about its effect by interacting with specific membrane receptor,the IL-11 receptorαchain (IL-11Rα) and the signalling component,gp130. IL-11 and IL-11Rαare very important in the process of mammalian reproduction.They play important roles in mammalian embryo implantation, decidualization and placentation.Female mice lacking the IL-11Rαgene are infertile due to a defective uterine response to the implanting blastocyst which is characterized by severely limited stromal differentiation,followed by uncontrolled trophoblast invasion. Mutant deciduae degenerate progressively, and consequently embryo-derived trophoblast cells generate a network of trophoblast giant cells but fail to form a chorioallantoic placenta.Further study demonstrated that defects in IL-11Rαinterfere with the efficiency of decidualization and negatively impact two processes characteristic of postimplantation pregnancy:decidual vascularization and uterine NK cell differentiation. However, the expression and regulation of Hoxa10 in canine reproduction are still undefined.IL-11RαmRNA was mainly localized in glandular epithelium and placenta in canine uterus.There was moderate level of IL-11Rαexpression in the glandular epithelium on days 6 of pregnancy and gradually decreased to a basal level from day 12 and 17 of pregnancy. On day 20 of pregnancy when embryo implanted, IL-11RαmRNA was highly expressed in the glandular epithelium. On day 23 of pregnancy the expression of IL-11RαmRNA maintains a constant level compared to the expression of day 20 and increased on day 28 of pregnancy. During the estrous cycle, a high level of IL-11RαmRNA expression was seen in the estrous uterus. There was a low level expression of IL-11RαmRNA in the uterus of ovariectomized canine. IL-11RαmRNA expression was not detected after estrogen treatment. However, IL-11RαmRNA signals were strongly detected in the glandular epithelium,after the overiectomized canines were treated with progesterone.These present study suggests that IL-11Rαmight play an important role during canine implantation and in the maintenance of early pregnancy. Progesterone can up-regulate the expression of IL-11Rαand estrogen down-regulate the expression of IL-11Rαin the ovariectomized canine uterus.