title: Polyethylene glycated leukemia inhibitory factor antagonist inhibits human blastocyst implantation and triggers apoptosis by down-regulating embryonic AKT.
abstract: OBJECTIVE
  To study the effect of polyethylene glycated leukemia inhibitory factor (LIF) antagonist (PEGLA) in the human blastocyst viability and implantation process.
  
  
  METHODS
  In vitro study.
  
  
  METHODS
  University hospital and research laboratory.
  
  
  METHODS
  Endometrial biopsy samples from fertile donors (n = 20), and surplus, frozen, good-quality human embryos obtained from an in vitro fertilization (IVF) clinic that survived thawing (n = 51).
  
  
  METHODS
  Timed human endometrial biopsy on the day of luteinizing hormone peak + 4 days (LH + 4).
  
  
  METHODS
  Human embryo attachment rate, embryo quality, and expression of AKT and caspase-3.
  
  
  RESULTS
  PEGLA significantly reduced the embryo attachment rate to the endometrial construct. It decreased both mRNA and protein for LIF in the endometrial construct. Inhibition of embryonic LIF triggered apoptosis. Analysis of these blastocysts by immunofluorescence and real-time polymerase chain reaction showed a down-regulation in AKT activation and an increase in caspase-3 activation compared with the control group of blastocysts.
  
  
  CONCLUSIONS
  The LIF inhibitor PEGLA could be a potential nonsteroidal fertility-regulating agent in humans. It acts on endometrial epithelial cells by down-regulating endometrial epithelial LIF. Inhibition of blastocyst LIF decreased its cell survival factor p-AKT and increased apoptosis (cleaved caspase-3). This highlights that embryonic LIF is vital for human embryo implantation.
authors.affiliation: Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Sujata
authors.initials: S
authors.lastname: Lalitkumar
authors.forename: Nageswara R
authors.initials: NR
authors.lastname: Boggavarapu
authors.forename: Judith
authors.initials: J
authors.lastname: Menezes
authors.forename: Evdokia
authors.initials: E
authors.lastname: Dimitriadis
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Zhang
authors.forename: Nicos A
authors.initials: NA
authors.lastname: Nicola
authors.forename: Kristina
authors.initials: K
authors.lastname: Gemzell-Danielsson
authors.forename: Luther P G
authors.initials: LP
authors.lastname: Lalitkumar
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001706:Biopsy; D001755:Blastocyst / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D015536:Down-Regulation; D046149:Embryo Culture Techniques; D010064:Embryo Implantation / Q000187:drug effects*; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D053605:Leukemia Inhibitory Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology*; D010766:Phosphorylation; D011092:Polyethylene Glycols / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D012333:RNA, Messenger; C525879:pegylated MH35-BD-Q29A+G124R protein; D011092:Polyethylene Glycols; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; C505407:CASP3 protein, human; D053148:Caspase 3
keywords: AKT; LIF; PEGLA; apoptosis; embryo attachment