The immune environment in human endometrium during the window of implantation.
OBJECTIVE
Changes in the immune environment in the endometrium are believed to be important for successful implantation and maintenance of pregnancy. We have previously investigated global gene profiling in human endometrium during the window of implantation by oligonucleotide microarray technology, and analysis of these data underscore the regulation of a group of immune-related genes. The present study was therefore conducted to examine the pattern of expression and regulation of these genes including decay accelerating factor (DAF), indoleamine 2,3 dioxygenase (IDO), interleukin-15 (IL-15), IL-15 receptor alpha subunit (IL-15Ralpha), interferon regulatory factor-1 (IRF-1), lymphotactin (Lpn), natural killer-associated transcript 2 (NKAT2) and NKG5 in secretory and proliferative human endometrium.


METHODS
Endometrial biopsies were obtained from normally cycling women in the late proliferative and mid-secretory phase of the menstrual cycle. Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and Northern blot analysis were used to determine the expression and regulation of these genes in secretory and proliferative human endometrium. Cellular localization of NKG5, Lpn and IDO by in situ hybridization in secretory-phase endometrium was also examined.


RESULTS
Semi-quantitative RT-PCR and Northern blot results demonstrate that there is a coordinated upregulation of this group of genes during the window of implantation.


CONCLUSIONS
We demonstrate the upregulation of immune-related genes IL-15Ralpha, Lpn and NKG5 in secretory versus proliferative human endometrium. We also demonstrate a similar upregulation in secretory endometrium of other immune-related genes, viz, DAF, IDO, IL-15, IRF-1 and NKAT2. The functions of these genes include stimulation of proliferation of uterine natural killer (uNK) cells, inhibition of cytolytic activity of uNK cells, inhibition of cell growth of T cells and other pathogens and inhibition of the classical complement pathway. Upregulation of these immune-related genes in the window of implantation suggests their role during the process of implantation and in immune tolerance of the implanting conceptus.
Lobo
Shalini C
SC
Department of Gynecology and Obstetrics, Stanford University Medical Center, Stanford, CA 94305-5317, USA.
Huang
S-T Joseph
ST
Germeyer
Ariane
A
Dosiou
Chrysoula
C
Vo
Kim Chi
KC
Tulac
Suzana
S
Nayak
Nihar R
NR
Giudice
Linda C
LC
D015152:Blotting, Northern; D010064:Embryo Implantation / Q000276:immunology*; D004717:Endometrium / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020133:Reverse Transcriptase Polymerase Chain Reaction