Heparin-Binding Epidermal Growth Factor–Like Growth Factor Enhances Aquaporin 3 Expression and Function During Mouse Embryo Implantation

• Published in: Reproductive sciences (Thousand Oaks, Calif.) Vol. 24; no. 3; pp. 463 - 470
• Main Authors: Fang, Chuan-Xiang, Nong, Ying-Qi, Liu, Feng-Hua, Fan, Lin, Chen, Ye
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.03.2017; Springer International Publishing
• Subjects: Animals; Aquaporin 3 - metabolism; Blastocyst - drug effects; Blastocyst - metabolism; Coculture Techniques; Copper Sulfate - pharmacology; Embryo Implantation - drug effects; Embryo Implantation - physiology; Embryology; Endometrium - drug effects; Endometrium - metabolism; Female; Heparin-binding EGF-like Growth Factor - pharmacology; Medicine & Public Health; Mice; Obstetrics/Perinatology/Midwifery; Original Article; Phosphorylation - drug effects; Receptor, Epidermal Growth Factor - metabolism; Reproductive Medicine; Signal Transduction - drug effects; aquaporin 3; heparin-binding epidermal growth factor–like growth factor; outgrowth; attachment; embryo implantation; heparin-binding epidermal growth factor-like growth factor
• ISSN: 1933-7191; 1933-7205
• DOI: 10.1177/1933719116657893

Aquaporin 3 (AQP3) is highly expressed in peri-implantation blastocyst trophoblastic cells, indicating its role in cytotrophoblast invasion during embryo implantation. However, the mechanism underlying the regulation of AQP3 expression during embryo implantation remains unclear. In this study, an in vitro co-culture system of blastocysts on a monolayer of uterine endometrial cells was used to mimic in vivo process of embryo attachment and invasion to uterine endometrium and treated with different concentrations of heparin-binding epidermal growth factor–like growth factor (HB-EGF). The results showed that HB-EGF enhanced AQP3 expression in blastocysts in a dose-dependent manner and promoted the attachment and outgrowth of blastocysts on the monolayer of uterine endometrial cells. When the AQP3 activity was inhibited by copper sulfate, both the attachment and outgrowth of blastocysts were inhibited. Furthermore, HB-EGF induced the phosphorylation of EGF receptor (EGFR) and extracellular signal–regulated kinase (ERK). PD153035 (EGFR inhibitor) and U0126 (ERK inhibitor) inhibited AQP3 expression and also the attachment and outgrowth of blastocysts. Collectively, our findings provide the first evidence that HB-EGF stimulates EGFR/ERK signaling to promote AQP3 expression in trophoblastic cells, and AQP3 plays a vital role in HB-EGF-induced embryo implantation.