Different expression of MUC1, FGF2, HBEGF, CSF1, VEGFA in the female reproductive tract in women with and without ectopic pregnancy

Background: Establishment of viable pregnancy requires embryo implantation and placentation. Ectopic pregnancy (EP) implantation junction breakdown occur outside of the uterine cavity with around 98% implanting in the fallopian tube. Among the genes effective in implantation these genes (MUC1), (FGF2), (HB-EGF), (VEGF-A), (CSF-l) are of particular importance. This study aims to investigate mRNA expression of MUC1, FGF2, HB-EGF, VEGF-A, CSF-l in fallopian tubes and endometrium of women who have EP compared with fallopian tubes and endometrium of pseudo-pregnant women. We hypothesize that expression of this genes in human fallopian tubes and endometrium may change during EP. Colony‐stimulating factor 1 (csf1), a cytokine required for the differentiation, proliferation and survival of most macrophages, signals through a high‐affinity receptor, csf1r, that is expressed on macrophages and their precursors. Fibroblast growth factors (FGFs) that signal through FGF receptors (FGFRs) regulate a broad spectrum of biological functions, including cellular proliferation, survival, migration, and differentiation. Mucins are high molecular weight (MW) glycoproteins, which contain at least 50% of carbohydrate O-linked to a threonine/serine rich peptide core. MUC1 functions include lubrication and protection against pathogens. Vascular endothelial growth factor (VEGF) is a potent antigenic factor responsible for vascular development that acts through its receptors. HBEGF is a member of the EGF family, which includes proteins that bind to tyrosine kinase receptors of the human EGF receptor (ERBB) family. HBEGF contributes to trophoblast survival and extra villous differentiation during early pregnancy, and is dysregulated in placental insufficiencies.Objective: Our aim is to evaluate the expression of these genes (MUC1, FGF2, HB-EGF, VEGF-A, CSF-l) in the endometrium and fallopian tube between the ectopic pregnancy and the control group (pseudo pregnancy).Materials and Methods: This was a case-control study. The case group consisted of women who underwent salpingectomy because of EP. The control group consisted of women with normal fallopian tubes that underwent hysterectomy. Prior to tubal sampling, each control subject received an injection of human chorionic gonadotropin (hCG) to produce a state of pseudo-pregnancy. Fallopian tubes and endometrial tissue from both groups were procured. We investigated VEGFA, MUC1, CSF1, FGF2 and HBEGF mRNA expressions in endometrial tissue and Ampulla section of the fallopian tube by Quantitative reverse transcriptase polymerase chain reaction (Q-RT-PCR).Results: Our results showed expressions of these genes in endometrial tissue and Ampulla section of the fallopian tube in both groups. The expression of MUC1, HBEGF, and FGF2 genes in both groups (endometrial and ampulla) was higher in the case group than control. The expression of VEGFA and CSF genes in the endometrium of the case group (EP) was higher than the control group and showed higher expression in the Ampulla of the control group.Conclusion: Different expression of current genes of EP groups in the fallopian tube and endometrium might have a role in the pathogenesis of embryo implantation in women who suffering from ectopic pregnancy. This investigation produce strong evidence of critical roles of molecular aspect which influences in fallopian tube implantation.

Keywords:

Ectopic Pregnancy , Fallopian Tube , Endometrium , Gene Expression , MUC1 , FGF2 , HB-EGF , VEGF-A , CSF-l