AQP7's Expression And Possible Function In Periimplantation Mouse Utrine

The aquaporins (AQPs) are a family of transmembrane proteins that transport water,the discovery of which provided molecular mechanisms for rapid water transport. AQP7 belongs to the aquaglyceroporin subfamily, which can transport water, glycerol, urea and other small solutes. Emerging evidences have shown important physiologic roles for aquaglyceroporins in facilitating glycerol transport in many tissues, including skin, adipocyte, liver, and intestine. One novel concept raised from these studies is that the aquaglyceroporins could facilitate glycerol transport at the cellular level, thus providing glycerol as a substrate for cell energy metabolism, especially in tissues where rapid cell turnover is involved, such as intestinal epithelial regeneration and skin tumorigenesis. During mouse embryo implantation, the endometrium undergoes progressive stromal cell decidualization initiating at the site of embryo attachment, a process that involves complex cellular changes characterized by extensive stromal cell proliferation and differentiation into decidual cells, along with vascular angiogenesis, and the uterus undergoes a substantial increase in volume and weight in a few days, a process somewhat similar to tumor growth regarding cellular behavior and energy metabolism. It is our hypothesis that the process of uterine decidualization might utilize glycerol as an extra energy source through aquaglyceroporin-facilitated glycerol transport. By using in situ hybridization, immunofluorescence, realtime PCR and so on, we investigated the spatial-temporal expression of AQP7 in mouse decidualization process and explored its possible role.The in situ hybridization results showed that there was no obvious expression of AQP7 in D4 uterus, while it showed expanding expression in decidual cells along with decidualization process in D5-D8 uteri. The immunofluorescence results showed a consistent expression pattern comparing with in situ hybridization. Notably, when AQP7 initially appeared in the decidual cells at D5, its localization was intensely confined in the cells surrounding implantation site, with a spotty-like distribution. From D6 to D8, AQP7 became extensively expressed in the primary decidual zone (PDZ). During this period, AQP7 expression showed a region specific pattern: while the peripheral expression region showed spotty-like signal similar to D5, the sub-luminal stroma surrounding the implantation site showed a distinct pattern with strong cell plasma membrane staining. These results showed that there were spatial-temporal expression of AQP7 mRNA and protein in mouse uterus. The expression pattern of AQP7 in artificial decidualization mouse uteri is strikingly similar with that observed in normal decidualization, suggesting that AQP7 induction in uteri is not embryo dependent, but mainly dependent on uterine decidualization process. In in vitro decidualization model, the AQP7 positive cells were increased with the progression of decidualization in a time dependent manner. All these results showed strong relationship between AQP7 expression and decidualization. Since AQP7 is an aquaglyceroporin, we next examined the uterine glycerol contents and glycerol kinase (gyk) mRNA expression during early pregnancy from D4 to D8, and both of them showed significant increase during postimplantation as revealed by linear regression analysis.In summary, the present data demonstrated that the AQP7 is dynamically expressed in mouse decidualizing uteri at post-implantation, and the process of uterine decidualization might involve AQP7-facilitated glycerol accumulation and increased gyk expression, suggesting a possibility that uterine decidualization might use glycerol as a potential energy substrate for extensive cell growth.