title: Triptorelin and cetrorelix induce immune responses and affect uterine development and expressions of genes and proteins of ESR1, LHR, and FSHR of mice.
abstract: BACKGROUND
  GnRH immunity can reduce the expression of pituitary GnRH levels, and cause the changes in reproductive behaviors. It is unclear whether triptorelin (TRI) and cetrorelix (CET) immunity influences uterine development and expression of follicle-stimulating hormone receptor (FSHR), luteinizing hormone receptor (LHR), and estradiol receptor 1 (ERS1) in the uterus.
  
  
  OBJECTIVE
  The study investigated the effects of active immunity of GnRH agonist and antagonist on uterine development, microstructures, expression of hormone receptors mRNAs, and proteins in uteri.
  
  
  METHODS
  One hundred and five mice were assigned into CET, TRI, and control groups (CG). Mice in CET-1, CET-2, and CET-3 (n = 15) were subcutaneously injected with 10, 20, and 40 μg CET antigens for seven days, respectively. Mice in TRI-1, TRI-2, and TRI-3 were injected with 10, 20, and 40 μg TRI antigens for seven days, respectively. The qPCR and Western blot were implemented to determine expressions of ESR1, LHR and FSHR mRNAs, and proteins.
  
  
  RESULTS
  Compared with CG, the uterine weights of CET-1, CET-2, and CET-3 increased by 42.86, 62.86, and 10.00% on day 35 (p < 0.05), respectively. Uterine weights of TRI-2, TRI-3 reduced by 28.57% and 11.43% (p < 0.05), respectively. The uterine cavity in CET-1, CET-2, and CET-3 increased; the uterine wall became thick. The cytoplasm of endometrial epithelial cells (EEC) increased slightly. In TRI group, the uterine wall thinned. Uterine cavity became narrow slightly in TRI-1. Numbers of uterine glands reduced. The endometrium epithelial thickness (EET) in CET-1 and CET-2 increased by 68.21% and 79.46% (p < 0.05), respectively. EET in TRI-1 was decreased by 13.69%. Uterine wall thicknesses (UWT) in CET-1 and CET-2 were higher than CG, with the increment of 28.59% and 30.72%. UWT of TRI-1, TRI-2, and TRI-3 reduced by 29.35, 15.36, and 14.41%, respectively. Expressions of ESR1, FSHR, and LHR mRNAs in CET and TRI mice increased. ESR1 and FSHR protein levels increased in all experimental mice (p < 0.05), with a maximum of TRI-3. LHR protein levels of the CET decreased. LHR protein levels of TRI group increased, with a maximum of TRI-3 (p < 0.05). ESR1 protein level had significant negative correlations to mRNA expressions of ESR1, LHR, and FSHR.
  
  
  CONCLUSIONS
  CET immunity promoted the uterine development, improved EET and UWT, and also promoted the expressions of ESR1 and FSHR protein levels. It lessened the LHR protein levels. TRI immunity blocked EET and UWT, inhibited uterine growth and development. The efficacy of CET immunity was more obvious than TRI.
authors.affiliation: a Engineering & Technology Research Center of Animal Cells of Gansu Province, Northwest University for Nationalities , Lanzhou , China ;|b Life Science and Engineering College, Northwest University for Nationalities , Lanzhou , China ;
authors.forename: Suocheng
authors.initials: S
authors.lastname: Wei
authors.affiliation: c Prevention and Control Center for Animal Diseases of Gansu Province , Lanzhou , China ;
authors.forename: Huiling
authors.initials: H
authors.lastname: Guo
authors.affiliation: d Medicine College, Northwest University for Nationalities , Lanzhou , China.
authors.forename: Zhuandi
authors.initials: Z
authors.lastname: Gong
authors.affiliation: b Life Science and Engineering College, Northwest University for Nationalities , Lanzhou , China ;
authors.forename: Fengwei
authors.initials: F
authors.lastname: Zhang
authors.affiliation: a Engineering & Technology Research Center of Animal Cells of Gansu Province, Northwest University for Nationalities , Lanzhou , China ;
authors.forename: Zhongren
authors.initials: Z
authors.lastname: Ma
mesh_terms: D000818:Animals; D047628:Estrogen Receptor alpha / Q000096:biosynthesis* / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000276:immunology; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D011962:Receptors, FSH / Q000096:biosynthesis* / Q000276:immunology; D011974:Receptors, LH / Q000096:biosynthesis* / Q000276:immunology; D017329:Triptorelin Pamoate / Q000494:pharmacology*; D014599:Uterus / Q000254:growth & development* / Q000276:immunology
chemical_list: D047628:Estrogen Receptor alpha; D011962:Receptors, FSH; D011974:Receptors, LH; D017329:Triptorelin Pamoate; D007987:Gonadotropin-Releasing Hormone; C062876:cetrorelix
keywords: Active immunity; cetrorelix; mice; microstructure; receptor; triptorelin; uterus