Abstract
Aim:
Aquaporin 8 (AQP8) is expressed within the female reproductive system but its physiological function reminds to be elucidated. This study investigates the role of AQP8 during pregnancy using AQP8-knockout (AQP8-KO) mice.
Methods:
Homozygous AQP8-KO mice were mated, and the conception rate was recorded. AQP8-KO pregnant mice or their offspring were divided into 5 subgroups according to fetal gestational day (7, 13, 16, 18 GD) and newborn. Wild type C57 pregnant mice served as the control group. The number of pregnant mice, total embryos and atrophic embryos, as well as fetal weight, placental weight and placental area were recorded for each subgroup. The amount of amniotic fluid in each sac at 13, 16, and 18 GD was calculated. Statistical significance was determined by analysis of variance of factorial design and chi-square tests.
Results:
Conception rates did not differ significantly between AQP8-KO and wild type mice. AQP8-KO pregnant mice had a significantly higher number of embryos compared to wild type controls. Fetal/neonatal weight was also significantly greater in the AQP8-KO group compared to age-matched wild type controls. The amount of amniotic fluid was greater in AQP8-KO pregnant mice than wild type controls, although the FM/AFA (fetal weight/amniotic fluid amount) did not differ. While AQP8-KO placental weight was significantly larger than wild type controls, there was no evidence of placental pathology in either group.
Conclusion:
The results suggest that AQP8 deficiency plays an important role in pregnancy outcome.
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References
Liu H, Wintour EM . Aquaporins in development — a review. Reprod Biol Endocrinol 2005; 3: 18–28.
Liu H, Zheng Z, Wintour EM . Aquaporins and fetal fluid balance. Placenta 2008; 29: 840–7.
Saparov SM, Liu K, Agre P, Pohl P . Fast and selective ammonia transport by aquaporin-8. J Biol Chem 2007; 282: 5296–301.
Itoh T, Rai T, Kuwahara M, Ko SB, Uchida S, Sasaki S, et al. Identification of a novel aquaporin, AQP12, expressed in pancreatic acinar cells. Biochem Biophys Res Commun 2005; 330: 832–8.
Ishibashi K, Kuwahara M, Kageyama Y, Tohsaka A, Marumo F, Sasaki S . Cloning and functional expression of a second new aquaporin abundantly expressed in testis. Biochem Biophys Res Commun 1997; 237: 714–8.
Koyama Y, Yamamoto T, Kondo D, Funaki H, Yaoita E, Kawasaki K, et al. Molecular cloning of a new aquaporin from rat pancreas and liver. J Biol Chem 1997; 272: 30329–33.
Ma T, Yang B, Verkman AS . Cloning of a novel water and urea–permeable aquaporin from mouse expressed strongly in colon, placenta, liver, and heart. Biochem Biophys Res Commun 1997; 240: 324–8.
Koyama N, Ishibashi K, Kuwahara M, Inase N, Ichioka M, Sasaki S, et al. Cloning and functional expression of human aquaporin 8 cDNA and analysis of its gene. Genomics 1998; 54: 169–72.
Calamita G, Mazzone A, Bizzoca A, Cavalier A, Cassano G, Thomas D, et al. Expression and immunolocalization of the aquaporin-8 water channel in rat gastrointestinal tract. Eur J Cell Biol 2001; 80: 711–9.
Calamita G, Mazzone A, Bizzoca A, Svelto M . Possible involvement of aquaporin-7 and -8 in rat testis development and spermatogenesis. Biochem Biophys Res Commun 2001; 288: 619–25.
Calamita G, Mazzone A, Cho YS, Valenti G, Svelto M . Expression and localization of the aquaporin-8 water channel in rat testis. Biol Reprod 2001; 64: 1660–6.
Elkjaer ML, Nejsum LN, Gresz V, Kwon TH, Jensen UB, Frokiaer J, et al. Immunolocalization of aquaporin-8 in rat kidney, gastrointestinal tract, testis, and airways. Am J Physiol Renal Physiol 2001; 281: F1047–57.
Hoque AT, Yamano S, Liu X, Swaim WD, Goldsmith CM, Delporte C, et al. Expression of the aquaporin 8 water channel in a rat salivary epithelial cell. J Cell Physiol 2002; 191: 336–41.
Hurley PT, Ferguson CJ, Kwon TH, Andersen ML, Norman AG, Steward MC, et al. Expression and immunolocalization of aquaporin water channels in rat exocrine pancreas. Am J Physiol Gastrointest Liver Physiol 2001; 280: G701–9.
Tani T, Koyama Y, Nihei K, Hatakeyama S, Ohshiro K, Yoshida Y, et al. Immunolocalization of aquaporin–8 in rat digestive organs and testis. Arch Histol Cytol 2001; 64: 159–68.
Liu H, Koukoulas I, Ross MC, Wang S, Wintour EM . Quantitative comparison of placental expression of three aquaporin genes. Placenta 2004; 25: 475–8.
Wang S, Chen J, Au KT, Ross MG . Expression of aquaporin 8 and its up-regulation by cyclic adenosine monophosphate in human WISH cells. Am J Obstet Gynecol 2003; 188: 997–1001.
Beall MH, Wang S, Yang B, Chaudhri N, Amidi F, Ross MG . Placental and membrane aquaporin water channels: correlation with amniotic fluid volume and composition. Placenta 2007; 28: 421–8.
Anderson J, Brown N, Mahendroo MS, Reese J . Utilization of different aquaporin water channels in the mouse cervix during pregnancy and parturition and in models of preterm and delayed cervical ripening. Endocrinology 2006; 147: 130–40.
Yeung CH, Callies C, Rojek A, Nielsen S, Cooper TG . Aquaporin isoforms involved in physiological volume regulation of murine spermatozoa. Biol Reprod 2009; 80: 350–7.
Yeung CH, Callies C, Tüttelmann F, Kliesch S, Cooper TG . Aquaporins in the human testis and spermatozoa — identification, involvement in sperm volume regulation and clinical relevance. Int J Androl 2010; 33: 629–41.
McConnell NA, Yunus RS, Gross SA, Bost KL, Clemens MG, Hughes FM Jr . Water permeability of an ovarian antral follicle is predominantly transcellular and mediated by aquaporins. Endocrinology 2002; 143: 2905–12.
Brañes MC, Morales B, RÃos M, Villalón MJ . Regulation of the immunoexpression of aquaporin 9 by ovarian hormones in the rat oviductal epithelium. Am J Physiol Cell Physiol 2005; 288: C1048–57.
Jablonski EM, McConnell NA, Hughes FM Jr, Huet-Hudson YM . Estrogen regulation of aquaporins in the mouse uterus: potential roles in uterine water movement. Biol Reprod 2003; 69: 1481–7.
Wang S, Kallichanda N, Song W, Ramirez BA, Ross MG . Expression of aquaporin-8 in human placenta and chorioamniotic membranes: evidence of molecular mechanism for intramembranous amniotic fluid resorption. Am J Obstet Gynecol 2001; 185: 1226–31.
Yang B, Song Y, Zhao D, Verkman AS . Phenotype analysis of aquaporin-8 null mice. Am J Physiol Cell Physiol 2005; 288: C1161–70.
Su W, Qiao Y, Yi F, Guan X, Zhang D, Zhang S, et al. Increased female fertility in aquaporin 8-deficient mice. IUBMB Life 2010; 62: 852–7.
Burghardt B, Nielsen S, Steward MC . The role of aquaporin water channels in fluid secretion by the exocrine pancreas. J Membr Biol 2006; 210: 143–53.
Mann SE, Ricke EA, Torres EA, Taylor RN . A novel model of polyhydramnios: amniotic fluid volume is increased in aquaporin 1 knockout mice. Am J Obstet Gynecol 2005; 192: 2041–6.
Ye X, Hama K, Contos JJ, Anliker B, Inoue A, Skinner MK, et al. LPA3-mediated lysophosphatidic acid signalling in implantation and embryo spacing. Nature 2005; 435: 104–8.
Acknowledgements
The authors thank Dr Alan S VERKMAN, Dr Xue-chao FENG, Lei GUO, and Wei-heng SU for their help and Song-ying SHEN and Xiao-yan XIA for data analysis assistance. This study was supported by the National Natural Sciences Foundation of China (No 30471828, 30973206) and the National Natural Science Funds for Distinguished Young Scholar (No 30325011).
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Sha, Xy., Xiong, Zf., Liu, Hs. et al. Pregnant phenotype in aquaporin 8-deficient mice. Acta Pharmacol Sin 32, 840–844 (2011). https://doi.org/10.1038/aps.2011.45
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DOI: https://doi.org/10.1038/aps.2011.45
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