Assessment of the proliferative status of epithelial cell types in the endometrium of young and menopausal transition women

Abstract

We determined protein and mRNA expressions of markers of normal human endometrial proliferation and hypothesized that dysregulation of the endometrial response to estradiol (E(2)) and progesterone would be observed in the older menopausal transition (MT) women compared with mid-reproductive age (MRA) controls. Endometrial biopsies were prospectively obtained from MRA and MT non-randomized healthy volunteers during proliferative (+/- exogenous E(2)) 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 dependent 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. 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. E(2)-treatment of MT women led to relatively less MKI67 glandular protein expression compared with MRA women; no other age-related differences were observed. 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.