title: Integrins β1 and β3 are biomarkers of uterine condition for embryo transfer.
abstract: Clinical ovulation induction induces blood estrogen (E2) in excess of physiological levels, which can hinder uterine receptivity. In contrast, progesterone produces the opposite clinical effect, suggesting that it might be capable of recovering the lost receptivity resulting from exposure to high estrogen levels. Integrins are the most widely used biological markers for monitoring uterine conditions. We studied progesterone-induced changes in integrin β expression patterns as biomarkers for changes in uterine receptivity in response to increased estrogen levels.
  
  
  
  Endometrial biopsy samples from patients were screened for their estrogen (E2) and progesterone (P4) content and expressing levels of integrin β1 and β3. Uterine receptivity was evaluated using human endometrial adenocarcinoma cells in an embryo attachment model. The respective and concatenated effects of embryo attachment and changes in the integrin β1 and β3 expression patterns on the adenocarcinoma cell plasma membranes in response to 100 nM concentrations of E2and P4 were evaluated.
  
  
  
  Increased blood E2concentrations were associated with significantly decreased the levels of integrin β3 expression in uterine biopsy samples. In vitro experiments revealed that a 100 nM E2concentration inhibited the distribution of integrin β3 on the plasma membranes of human endometrial adenocarcinoma cells used in the embryo attachment model, and resulted in decreased rates of embryo attachment. In contrast, P4 enhanced the expression of integrin β1 and promoted its distribution on the plasma membranes. Furthermore, P4 recovered the embryo attachment efficiency that was lost by exposure to 100 nM E2.
  
  
  
  Blood E2 and P4 levels and integrin β3 and β1 expression levels in uterine biopsy samples should be considered as biomarkers for evaluating uterine receptivity and determining the optimal time for embryo transfer. Trial registration Trial number: ChiCTR-TRC-13003777; Name of registry: Chinese Clinical Trial Registry; Date of registration: 4 September 2013; Date of enrollment of the first study participant: 15 October 2013.
authors: Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, China.
authors: Guowu
authors: G
authors: Chen
authors: Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, China.|Shanghai Ji Ai Genetics and IVF Institute, Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, 200011, China.
authors: Aijie
authors: A
authors: Xin
authors: Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, China.|Shanghai Ji Ai Genetics and IVF Institute, Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, 200011, China.
authors: Yulin
authors: Y
authors: Liu
authors: China National Population and Family Planning Key Laboratory of Contraceptive Drugs and Devices, SIPPR, Shanghai, 200032, China.
authors: Changgen
authors: C
authors: Shi
authors: Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, China.|Shanghai Ji Ai Genetics and IVF Institute, Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, 200011, China.
authors: Junling
authors: J
authors: Chen
authors: Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, China.|Shanghai Ji Ai Genetics and IVF Institute, Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, 200011, China.
authors: Xiaofeng
authors: X
authors: Tang
authors: Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, China.|Shanghai Ji Ai Genetics and IVF Institute, Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, 200011, China.
authors: Ying
authors: Y
authors: Chen
authors: Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, China.|Shanghai Ji Ai Genetics and IVF Institute, Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, 200011, China.
authors: Min
authors: M
authors: Yu
authors: Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, China.|Shanghai Ji Ai Genetics and IVF Institute, Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, 200011, China.
authors: Xiandong
authors: X
authors: Peng
authors: Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, China.|Shanghai Ji Ai Genetics and IVF Institute, Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, 200011, China.
authors: Lu
authors: L
authors: Li
authors: Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, China. sunxiaoxi_sci@qq.com.|Shanghai Ji Ai Genetics and IVF Institute, Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, 200011, China. sunxiaoxi_sci@qq.com.|Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, China. sunxiaoxi_sci@qq.com.
authors: Xiaoxi
authors: X
authors: Sun
mesh_terms: D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003710:Demography; D010064:Embryo Implantation / Q000187:drug effects; D004624:Embryo Transfer; D004958:Estradiol / Q000378:metabolism; D005260:Female; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D039661:Integrin beta3 / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D011374:Progesterone / Q000008:administration & dosage / Q000378:metabolism; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D006063:Chorionic Gonadotropin; D019012:Integrin beta1; D039661:Integrin beta3; D011374:Progesterone; D004958:Estradiol
keywords: Biomarkers; Concatenated progesterone effect; Integrin β1; Integrin β3; Uterine receptivity