Decreased expression of aquaporin 2 is associated with impaired endometrial receptivity in controlled ovarian stimulation

Reprod Fertil Dev. 2016 Mar;28(4):499-506. doi: 10.1071/RD13397.

Abstract

Recently, there has been evidence of decreased implantation rates with in vitro fertilisation and embryo transfer due to controlled ovarian stimulation (COS). The aim of this study was to investigate the effect of COS on embryo implantation and the role of aquaporin 2 (AQP2). We recruited eight patients who underwent COS and 40 matched controls. Endometrial samples were collected on Day 4~8 after injection of human chorionic gonadotrophin in the COS group and in the mid-secretory phase in the control group. Human endometrial morphological changes after COS were examined and expression of AQP2, leukaemia inhibitory factor (LIF) and integrin B3 (ITGB3) were determined by quantitative polymerase chain reaction, western blotting and immunohistochemistry in human endometrium and Ishikawa cells. Attachment rates were obtained using the embryo attachment test. The results showed that endometrial epithelial cells from the COS group were disrupted and lacked pinopodes. Messenger RNA and protein levels of AQP2, LIF and ITGB3 decreased in endometrial samples from the COS group. Knockdown of AQP2 resulted in reduced expression of LIF and ITGB3 and reduced embryo attachment rates. In conclusion, impaired endometrial receptivity in patients who underwent COS is correlated with a decreased expression of AQP2.

MeSH terms

  • Animals
  • Aquaporin 2 / genetics
  • Aquaporin 2 / metabolism*
  • Case-Control Studies
  • Cells, Cultured
  • Chorionic Gonadotropin / adverse effects*
  • Down-Regulation
  • Embryo Culture Techniques
  • Embryo Implantation, Delayed*
  • Endometrium / drug effects*
  • Endometrium / metabolism
  • Endometrium / pathology
  • Female
  • Fertility Agents, Female / adverse effects*
  • Humans
  • Leukemia Inhibitory Factor / genetics
  • Leukemia Inhibitory Factor / metabolism
  • Mice
  • Ovulation Induction / adverse effects*
  • Pregnancy
  • RNA Interference
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Time Factors
  • Transfection
  • Transforming Growth Factor beta3 / genetics
  • Transforming Growth Factor beta3 / metabolism

Substances

  • AQP2 protein, human
  • Aquaporin 2
  • Chorionic Gonadotropin
  • Fertility Agents, Female
  • LIF protein, human
  • Leukemia Inhibitory Factor
  • RNA, Messenger
  • TGFB3 protein, human
  • Transforming Growth Factor beta3