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RESEARCH ARTICLE
Contents Vol 35(14)

Aquaporin 7 is upregulated through the PI3K-Akt pathway and modulates decidualisation of endometrial stromal cells

Min Liu https://orcid.org/0000-0001-9200-3265 A * , Yong-Jie Mi A and Juan Dai B
+ Author Affiliations
- Author Affiliations

A National Demonstration Centre for Experimental Clinical Medicine Education, Chengdu Medical College, Chengdu, People’s Republic of China.

B College of Laboratory Medicine, Chengdu Medical College, Chengdu, People’s Republic of China.

* Correspondence to: qwlmin@163.com

Handling Editor: Gilles Charpigny

Reproduction, Fertility and Development 35(14) 669-675 https://doi.org/10.1071/RD23054
Published online: 26 October 2023

© 2023 The Author(s) (or their employer(s)). Published by CSIRO Publishing

Abstract

Context

Aquaporin 7 (AQP7) is selectively expressed in decidualised endometrial stromal cells (ESCs) of mice surrounding the embryonic implantation sites. However, the roles of AQP7 and the underlying mechanism that regulates AQP7 expression in endometrial decidualisation after implantation are still unclear.

Aims

This study aimed to investigate the role of the PI3K-Akt pathway in regulating the expression of AQP7 in ESCs and decidualisation.

Methods

Primary ESCs of pregnant mice were isolated to establish in vitro decidualisation models. PI3K inhibitor LY294002 was added to the decidualisation models, then AQP7 expression, changes in decidualised ESC morphology and expression of decidualisation marker molecules were examined.

Key results

AQP7 knockdown reduced the proliferation and differentiation of ESCs with in vitro induced decidualisation. Furthermore, when the activity of PI3K was inhibited by LY294002, the expression of AQP7 in decidualised ESCs was decreased and both the proliferation and differentiation of ESCs were significantly reduced.

Conclusions

This indicates that AQP7 is a key molecule involved in endometrial decidualisation and the expression of AQP7 is upregulated through activation of the PI3K-Akt pathways, which promotes the proliferation and differentiation of the ESCs, thus affecting occurrence of decidualisation.

Implications

This study may provide a new biomarker for the diagnosis of infertility and a new drug target for the prevention and treatment of infertility.

Keywords: AQP7, decidualisation, decidualised ESCs, decidualised stromal cells, early pregnancy, endometrial stromal cells, glycerol aquaporins, implantation, infertility, phosphoinositide 3 kinase.

References

Agre P, King LS, Yasui M, Guggino WB, Ottersen OP, Fujiyoshi Y, Engel A, Nielsen S (2002) Aquaporin water channels – from atomic structure to clinical medicine. The Journal of Physiology 542(1), 3-16.
| Crossref | Google Scholar |

Chinigarzadeh A, Muniandy S, Salleh N (2016) Estradiol, progesterone and genistein differentially regulate levels of aquaporin (AQP)-1, 2, 5 and 7 expression in the uteri of ovariectomized, sex-steroid deficient rats. Steroids 115, 47-55.
| Crossref | Google Scholar |

Chinigarzadeh A, Muniandy S, Salleh N (2017) Combinatorial effect of genistein and female sex-steroids on uterine fluid volume and secretion rate and aquaporin (AQP)-1, 2, 5, and 7 expression in the uterus in rats. Environmental Toxicology 32(3), 832-844.
| Crossref | Google Scholar | PubMed |

Das SK (2009) Cell cycle regulatory control for uterine stromal cell decidualization in implantation. Reproduction 137(6), 889-899.
| Crossref | Google Scholar | PubMed |

Fujiki K, Inamura H, Matsuoka M (2014) PI3K signaling mediates diverse regulation of ATF4 expression for the survival of HK-2 cells exposed to cadmium. Archives of Toxicology 88(2), 403-414.
| Crossref | Google Scholar |

Han L, Yang Y, Yue X, Huang K, Liu X, Pu P, Jiang H, Yan W, Jiang T, Kang C (2010) Inactivation of PI3K/AKT signaling inhibits glioma cell growth through modulation of β-catenin-mediated transcription. Brain Research 1366, 9-17.
| Crossref | Google Scholar |

Hara-Chikuma M, Verkman AS (2008) Prevention of skin tumorigenesis and impairment of epidermal cell proliferation by targeted aquaporin-3 gene disruption. Molecular and Cellular Biology 28(1), 326-332.
| Crossref | Google Scholar | PubMed |

Hibuse T, Maeda N, Nagasawa A, Funahashi T (2006) Aquaporins and glycerol metabolism. Biochimica et Biophysica Acta (BBA) - Biomembranes 1758(8), 1004-1011.
| Crossref | Google Scholar | PubMed |

Huang H-F, He R-H, Sun C-C, Zhang Y, Meng Q-X, Ma Y-Y (2006) Function of aquaporins in female and male reproductive systems. Human Reproduction Update 12(6), 785-795.
| Crossref | Google Scholar | PubMed |

Khan S, Ricciardelli C, Yool AJ (2021) Targeting aquaporins in novel therapies for male and female breast and reproductive cancers. Cells 10(2), 215.
| Crossref | Google Scholar | PubMed |

Kotova PD, Kochkina EN, Lyamin OO, Rogachevskaja OA, Korolenko NP, Ivashin DS, Bystrova MF, Enukashvily NI, Kolesnikov SS (2020) Calcium signaling mediated by aminergic GPCRs is impaired by the PI3K inhibitor LY294002 and its analog LY303511 in a PI3K-independent manner. European Journal of Pharmacology 880, 173182.
| Crossref | Google Scholar |

Lim HJ, Wang H (2010) Uterine disorders and pregnancy complications: insights from mouse models. The Journal of Clinical Investigation 120(4), 1004-1015.
| Crossref | Google Scholar | PubMed |

Murakami K, Lee YH, Lucas ES, Chan Y-W, Durairaj RP, Takeda S, Moore JD, Tan BK, Quenby S, Chan JKY, Gargett CE, Brosens JJ (2014) Decidualization induces a secretome switch in perivascular niche cells of the human endometrium. Endocrinology 155(11), 4542-4553.
| Crossref | Google Scholar | PubMed |

Peng S, Li J, Miao C, Jia L, Hu Z, Zhao P, Li J, Zhang Y, Chen Q, Duan E (2008) Dickkopf-1 secreted by decidual cells promotes trophoblast cell invasion during murine placentation. Reproduction 135(3), 367-375.
| Crossref | Google Scholar | PubMed |

Peng H, Zhang Y, Lei L, Chen Q, Yue J, Tan Y, Duan E (2011) Aquaporin 7 expression in postimplantation mouse uteri: a potential role for glycerol transport in uterine decidualization. Fertility and Sterility 95(4), 1514-1517.e3.
| Crossref | Google Scholar |

Preston GM, Agre P (1991) Isolation of the cDNA for erythrocyte integral membrane protein of 28 kilodaltons: member of an ancient channel family. Proceedings of the National Academy of Sciences of the United States of America 88(24), 11110-11114.
| Crossref | Google Scholar | PubMed |

Ramathal CY, Bagchi IC, Taylor RN, Bagchi MK (2010) Endometrial decidualization: of mice and men. Seminars in Reproductive Medicine 28(1), 17-26.
| Crossref | Google Scholar | PubMed |

Richard C, Gao J, Brown N, Reese J (2003) Aquaporin water channel genes are differentially expressed and regulated by ovarian steroids during the periimplantation period in the mouse. Endocrinology 144, 1533-1541.
| Crossref | Google Scholar | PubMed |

Rodríguez A, Catalan V, Gómez-Ambrosi J, García-Navarro S, Rotellar F, Valentí V, Silva C, Gil MJ, Salvador J, Burrell MA, Calamita G, Malagón MM, Frühbeck G (2011) Insulin- and leptin-mediated control of aquaglyceroporins in human adipocytes and hepatocytes is mediated via the PI3K/Akt/mTOR signaling cascade. The Journal of Clinical Endocrinology & Metabolism 96(4), E586-E597.
| Crossref | Google Scholar |

Rodríguez A, Moreno NR, Balaguer I, Méndez-Giménez L, Becerril S, Catalán V, Gómez-Ambrosi J, Portincasa P, Calamita G, Soveral G, Malagón MM, Frühbeck G (2015) Leptin administration restores the altered adipose and hepatic expression of aquaglyceroporins improving the non-alcoholic fatty liver of ob/ob mice. Scientific Reports 5, 12067.
| Crossref | Google Scholar |

Salleh N, Mokhtar HM, Kassim NM, Giribabu N (2015) Testosterone induces increase in aquaporin (AQP)-1, 5, and 7 expressions in the uteri of ovariectomized rats. The Journal of Membrane Biology 248(6), 1097-1105.
| Crossref | Google Scholar | PubMed |

Shahzad H, Giribabu N, Karim K, Kassim N, Muniandy S, Kumar KE, Salleh N (2017) Quercetin interferes with the fluid volume and receptivity development of the uterus in rats during the peri-implantation period. Reproductive Toxicology 71, 42-54.
| Crossref | Google Scholar | PubMed |

Suzuki M, Shibata Y, Ogushi Y, Okada R (2015) Molecular machinery for vasotocin-dependent transepithelial water movement in amphibians: aquaporins and evolution. The Biological Bulletin 229(1), 109-119.
| Crossref | Google Scholar | PubMed |

Tanski D, Skowronska A, Tanska M, Lepiarczyk E, Skowronski MT (2021) The in vitro effect of steroid hormones, arachidonic acid, and kinases inhibitors on aquaporin 1, 2, 5, and 7 gene expression in the porcine uterine luminal epithelial cells during the estrous cycle. Cells 10(4), 832.
| Crossref | Google Scholar |

Thiagarajah JR, Zhao D, Verkman AS (2007) Impaired enterocyte proliferation in aquaporin-3 deficiency in mouse models of colitis. Gut 56(11), 1529-1535.
| Crossref | Google Scholar | PubMed |

Verkman AS (2005) More than just water channels: unexpected cellular roles of aquaporins. Journal of Cell Science 118(15), 3225-3232.
| Crossref | Google Scholar |

Verkman AS, Mitra AK (2000) Structure and function of aquaporin water channels. American Journal of Physiology - Renal Physiology 278(1), F13-F28.
| Crossref | Google Scholar |

Zhang X, Fu L-J, Liu X-Q, Hu Z-Y, Jiang Y, Gao R-F, Feng Q, Lan X, Geng Y-Q, Chen X-M, He J-L, Wang Y-X, Ding Y-B (2016) nm23 regulates decidualization through the PI3K-Akt-mTOR signaling pathways in mice and humans. Human Reproduction 31(10), 2339-2351.
| Crossref | Google Scholar | PubMed |

Zhu C, Jiang Z, Bazer FW, Johnson GA, Burghardt RC, Wu GY (2015) Aquaporins in the female reproductive system of mammals. Frontiers in Bioscience 20(5), 838-871.
| Crossref | Google Scholar |