TY - JOUR
T1 - Assessment of the proliferative status of epithelial cell types in the endometrium of young and menopausal transition women
AU - Niklaus, Andrea L.
AU - Aubuchon, Mira
AU - Zapantis, Gregory
AU - Li, Ping
AU - Qian, Hong
AU - Isaac, Barbara
AU - Kim, Mimi Y.
AU - Adel, Goli
AU - Pollard, Jeffrey W.
AU - Santoro, Nanette F.
N1 - Funding Information:
We thank Liyin Zhu for technical advice and Dr James Bisley for useful discussions about the data. This work was supported by grants from the NIH RO1 AG12222 and K24 HD041978 (N.S.), NCI RO1 89617 (J.W.P.) and to the GCRC RR95261064.
PY - 2007/6
Y1 - 2007/6
N2 - Background: We determined protein and mRNA expressions of markers of normal human endometrial proliferation and hypothesized that dysregulation of the endometrial response to estradiol (E2) and progesterone would be observed in the older menopausal transition (MT) women compared with mid-reproductive age (MRA) controls. Methods: Endometrial biopsies were prospectively obtained from MRA and MT non-randomized healthy volunteers during proliferative (± exogenous E2) and secretory (MRA only) menstrual cycle phases. mRNA and/or nuclear protein expressions of proliferative markers (MKI67, PCNA and MCM2), cell-cycle regulators (cyclins A1, E1 and D1 and cyclin dependant kinase Inhibitor B; CCNA1, CCNE1, CCND1 and CDKN1B) and sex-steroid receptors [estrogen receptor (ER) and progesterone receptor (PR)] were assessed in endometrial lumen, gland and stroma. Results: MRA women had significantly higher proliferative than secretory expression of MKI67, PCNA, MCM2, CCNA1, CCNE1, ESR1 and PGR in lumen and gland (minimal stromal changes), whereas CDKN1B protein expression was higher during the secretory phase. E2-treatment of MT women led to relatively less MKI67 glandular protein expression compared with MRA women; no other age-related differences were observed. Conclusion: Although the MT does not appear to alter the proliferative cell phenotype of endometrial epithelium and stroma, the data suggest that prior to the MT, age is associated with a decrease in some proliferative markers and steroid receptor expression status within different endometrial cell types.
AB - Background: We determined protein and mRNA expressions of markers of normal human endometrial proliferation and hypothesized that dysregulation of the endometrial response to estradiol (E2) and progesterone would be observed in the older menopausal transition (MT) women compared with mid-reproductive age (MRA) controls. Methods: Endometrial biopsies were prospectively obtained from MRA and MT non-randomized healthy volunteers during proliferative (± exogenous E2) and secretory (MRA only) menstrual cycle phases. mRNA and/or nuclear protein expressions of proliferative markers (MKI67, PCNA and MCM2), cell-cycle regulators (cyclins A1, E1 and D1 and cyclin dependant kinase Inhibitor B; CCNA1, CCNE1, CCND1 and CDKN1B) and sex-steroid receptors [estrogen receptor (ER) and progesterone receptor (PR)] were assessed in endometrial lumen, gland and stroma. Results: MRA women had significantly higher proliferative than secretory expression of MKI67, PCNA, MCM2, CCNA1, CCNE1, ESR1 and PGR in lumen and gland (minimal stromal changes), whereas CDKN1B protein expression was higher during the secretory phase. E2-treatment of MT women led to relatively less MKI67 glandular protein expression compared with MRA women; no other age-related differences were observed. Conclusion: Although the MT does not appear to alter the proliferative cell phenotype of endometrial epithelium and stroma, the data suggest that prior to the MT, age is associated with a decrease in some proliferative markers and steroid receptor expression status within different endometrial cell types.
KW - Cell cycle
KW - Endometrium
KW - Laser-capture
KW - Menopausal transition
KW - Proliferation
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U2 - 10.1093/humrep/dem032
DO - 10.1093/humrep/dem032
M3 - Article
C2 - 17371803
AN - SCOPUS:34447333658
VL - 22
SP - 1778
EP - 1788
JO - Human reproduction (Oxford, England)
JF - Human reproduction (Oxford, England)
SN - 0268-1161
IS - 6
ER -