BACKGROUND: The aim of this study was to analyse the effects of an estradiol (E(2))-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 (ERalpha) 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 E(2) and progesterone were higher in the peripheral blood in AC than in NC. Also on day AC5, expressions of ERalpha, 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 E(2), and the rapid decrease between AC5 and AC7 suggests overstimulation with progesterone. CONCLUSIONS: In ACs, increased levels of E(2) 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.
- MeSH
- alfa receptor estrogenů metabolismus MeSH
- dospělí MeSH
- down regulace * MeSH
- endometrium metabolismus MeSH
- estrogeny farmakologie MeSH
- fertilizace in vitro * MeSH
- lidé MeSH
- menstruační cyklus metabolismus MeSH
- metaloproteinasy secernované do matrix genetika metabolismus MeSH
- receptory progesteronu metabolismus MeSH
- regulace genové exprese MeSH
- tkáňové inhibitory metaloproteinas genetika metabolismus MeSH
- tkáňový inhibitor metaloproteinasy 4 MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- práce podpořená grantem MeSH
- Názvy látek
- alfa receptor estrogenů MeSH
- estrogeny MeSH
- metaloproteinasy secernované do matrix MeSH
- MMP26 protein, human MeSH Prohlížeč
- receptory progesteronu MeSH
- tkáňové inhibitory metaloproteinas MeSH
OBJECTIVE: To examine possible estrogen dependent endometrial expression of MMP-26 in vitro. DESIGN: Experimental study. SETTING: Department of Obstetrics and Gynecology of the Palacky University Medical School and University Hospital, Olomouc, Czech Republic, Department of Obstetrics and Gynecology, University Hospital, Lund, Sweden. METHODS: We studied MMP-26 mRNA in 14 normal endometrial samples obtained from the proliferative phase of the menstrual cycle. Samples were cultured for five days either with estradiol alone or in combination with progesterone. Samples cultured with ethanol represented control groups. MMP-26 mRNA expression was examined in frozen samples using in situ hybridization. Immunohistochemistry was used to study the presence of estrogen and progesterone receptors in endometrial explants. RESULTS: MMP-26 mRNA expression was highest in fresh (non cultured) samples. Signal intensity decreased during the first two days of culture and was negligable in the following days. Nuclear intensity for estrogen and progesterone receptor was high after five days of culture. CONCLUSION: We did not find MMP-26 mRNA in vitro expression to be directly estrogen dependent.
- MeSH
- dospělí MeSH
- endometrium účinky léků metabolismus MeSH
- estradiol farmakologie MeSH
- folikulární fáze MeSH
- lidé MeSH
- matrixové metaloproteinasy metabolismus MeSH
- metaloproteinasy secernované do matrix MeSH
- progesteron farmakologie MeSH
- techniky in vitro MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- Názvy látek
- estradiol MeSH
- matrixové metaloproteinasy MeSH
- metaloproteinasy secernované do matrix MeSH
- MMP26 protein, human MeSH Prohlížeč
- progesteron MeSH
OBJECTIVE: To examine the expression pattern of some novel matrix metalloproteinases (MMPs) in cycling endometrium. DESIGN: Experimental study. SETTING: Department of Obstetrics and Gynecology of the Palacky University Medical School and University Hospital, Olomouc, Czech Republic, Department of Obstetrics and Gynecology, University Hospital, Lund, Sweden. METHODS: We studied MMP-12, -16, -17, -19 and -26 mRNA in 39 normal endometrial samples obtained across the menstrual cycle. Based on histological examination, all specimens were classified according to an ideal 28 day menstrual cycle as early (n=8), mid (n=6) and late (n=7) proliferative phase, early (n=4), mid (n=4) and late (n=8) secretory phase and menstrual (n=3) phase. Cycle variation was examined in frozen samples using in situ hybridization. RESULTS: Three distinct pattern of MMP mRNA expression were detected in cycling endometrium. MMP-12 was expressed predominantly in perimenstrual period, MMP-16, -17 and 19 were expressed throughout the cycle and MMP-26 was found to be maximal in periovulatory period. CONCLUSION: Different endometrial expression patterns of novel MMPs during menstrual cycle may indicate their specific roles for menstruation, endometrial growth and remodelling and implantation.
- MeSH
- dospělí MeSH
- endometrium enzymologie MeSH
- hybridizace in situ MeSH
- lidé středního věku MeSH
- lidé MeSH
- matrixové metaloproteinasy metabolismus MeSH
- menstruační cyklus metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- Názvy látek
- matrixové metaloproteinasy MeSH