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Endometrial expression of the estrogen-sensitive genes MMP-26 and TIMP-4 is altered by a substitution protocol without down-regulation in IVF patients.

Pilka, Radovan LU ; Oborna, I ; Lichnovsky, V ; Havelka, P ; Fingerova, H ; Eriksson, P ; Hansson, Stefan LU orcid and Casslén, Bertil LU (2006) In Human Reproduction 21(12). p.3146-3156
Abstract
BACKGROUND: The aim of this study was to analyse the effects of an estradiol (E2)–progesterone substitution protocol on the endometrial expression of estrogen-sensitive genes during the peri-implantation period. METHODS: Peripheral blood and endometrial biopsies were obtained from 13 infertile women both in a natural cycle (NC), on days 5 and 7 after ovulation (NC5, NC7), and in an artificial (substituted) cycle (AC), on days 5 and 7 of progesterone addition (AC5, AC7). Estrogen receptor-{alpha} (ER{alpha}) and progesterone receptor (PR) were assayed by immunohistochemistry. Matrix metalloproteinase-26 (MMP-26) mRNA and tissue inhibitor of metalloproteinase-4 (TIMP-4) mRNA were semiquantitatively assessed in tissue sections using in situ... (More)
BACKGROUND: The aim of this study was to analyse the effects of an estradiol (E2)–progesterone substitution protocol on the endometrial expression of estrogen-sensitive genes during the peri-implantation period. METHODS: Peripheral blood and endometrial biopsies were obtained from 13 infertile women both in a natural cycle (NC), on days 5 and 7 after ovulation (NC5, NC7), and in an artificial (substituted) cycle (AC), on days 5 and 7 of progesterone addition (AC5, AC7). Estrogen receptor-{alpha} (ER{alpha}) and progesterone receptor (PR) were assayed by immunohistochemistry. Matrix metalloproteinase-26 (MMP-26) mRNA and tissue inhibitor of metalloproteinase-4 (TIMP-4) mRNA were semiquantitatively assessed in tissue sections using in situ hybridization (ISH) and quantified in tissue extracts using real-time PCR. RESULTS: Levels of both E2 and progesterone were higher in the peripheral blood in AC than in NC. Also on day AC5, expressions of ER{alpha}, PR and MMP-26 mRNA (focally) were increased in the epithelium and TIMP-4 mRNA in the stroma. Expression levels of these genes dropped significantly between AC5 and AC7, but not between NC5 and NC7. Abnormally high levels in AC5 samples suggest overstimulation with E2, and the rapid decrease between AC5 and AC7 suggests overstimulation with progesterone. CONCLUSIONS: In ACs, increased levels of E2 in the blood exaggerate the endometrial expression of estrogen-sensitive genes, whereas higher levels of progesterone in the blood in the secretory phase exaggerate the drop in expression of these genes. Dramatic variations in the gene expression may not be optimal for the implantation process. (Less)
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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
estrogen/implantation/mRNA/progesterone receptor/regulation
in
Human Reproduction
volume
21
issue
12
pages
3146 - 3156
publisher
Oxford University Press
external identifiers
  • wos:000242271600018
  • scopus:33751370625
  • pmid:17012332
ISSN
0268-1161
DOI
10.1093/humrep/del180
language
English
LU publication?
yes
id
9191a0b0-89ba-4489-9cd2-fd47aae44ab4 (old id 162466)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17012332&dopt=Abstract
date added to LUP
2016-04-01 12:17:16
date last changed
2021-02-17 08:00:13
@article{9191a0b0-89ba-4489-9cd2-fd47aae44ab4,
  abstract     = {BACKGROUND: The aim of this study was to analyse the effects of an estradiol (E2)–progesterone substitution protocol on the endometrial expression of estrogen-sensitive genes during the peri-implantation period. METHODS: Peripheral blood and endometrial biopsies were obtained from 13 infertile women both in a natural cycle (NC), on days 5 and 7 after ovulation (NC5, NC7), and in an artificial (substituted) cycle (AC), on days 5 and 7 of progesterone addition (AC5, AC7). Estrogen receptor-{alpha} (ER{alpha}) and progesterone receptor (PR) were assayed by immunohistochemistry. Matrix metalloproteinase-26 (MMP-26) mRNA and tissue inhibitor of metalloproteinase-4 (TIMP-4) mRNA were semiquantitatively assessed in tissue sections using in situ hybridization (ISH) and quantified in tissue extracts using real-time PCR. RESULTS: Levels of both E2 and progesterone were higher in the peripheral blood in AC than in NC. Also on day AC5, expressions of ER{alpha}, PR and MMP-26 mRNA (focally) were increased in the epithelium and TIMP-4 mRNA in the stroma. Expression levels of these genes dropped significantly between AC5 and AC7, but not between NC5 and NC7. Abnormally high levels in AC5 samples suggest overstimulation with E2, and the rapid decrease between AC5 and AC7 suggests overstimulation with progesterone. CONCLUSIONS: In ACs, increased levels of E2 in the blood exaggerate the endometrial expression of estrogen-sensitive genes, whereas higher levels of progesterone in the blood in the secretory phase exaggerate the drop in expression of these genes. Dramatic variations in the gene expression may not be optimal for the implantation process.},
  author       = {Pilka, Radovan and Oborna, I and Lichnovsky, V and Havelka, P and Fingerova, H and Eriksson, P and Hansson, Stefan and Casslén, Bertil},
  issn         = {0268-1161},
  language     = {eng},
  number       = {12},
  pages        = {3146--3156},
  publisher    = {Oxford University Press},
  series       = {Human Reproduction},
  title        = {Endometrial expression of the estrogen-sensitive genes MMP-26 and TIMP-4 is altered by a substitution protocol without down-regulation in IVF patients.},
  url          = {http://dx.doi.org/10.1093/humrep/del180},
  doi          = {10.1093/humrep/del180},
  volume       = {21},
  year         = {2006},
}