Circulating hormones and estrous stage predict cellular and stromal remodeling in murine uterus

Abstract

The understanding of how estrogen and progesterone (P 4 ) drive uterine remodeling in rodents has largely been based on studies involving administration of exogenous hormones, using steroid receptor-deficient mice, or relying on vaginal smears. In all these cases, the actual serum levels of 17b-estradiol (E 2 ) and P 4 are not directly measured, and the relationship between physiological levels of female sex hormones and uterine remodeling in cycling mice has not been fully explored. Here, we measured the circulating levels of E 2 and P 4 in cycling mice and performed correlation analysis between hormone levels and epithelial and stromal uterine parameters, irrespective of the estrous stage. In parallel, these parameters were analyzed in relation to the more conventional method of vaginal smear classification of estrous stage. We found that circulating P 4 inversely correlated with uterine width, luminal epithelial proliferation, stromal apoptosis, and degradation of luminal epithelial basement membrane collagen type-IV. Circulating E 2 positively correlated with uterine width, stromal cell proliferation, and collagen type-I content, while it negatively correlated with glandular epithelial proliferation, loss of collagen type-IV surrounding glandular epithelium, and apoptosis in luminal, glandular, and stromal compartments. Our findings indicate that measuring P 4 or E 2 levels can predict many concurrent cellular and stromal events in the mouse uterus, suggesting that in naturally cycling mice cellular responses to hormone changes are not delayed, but occur very rapidly.

A novel shift in estrogen receptor expression occurs as estradiol suppresses inflammation-associated colon tumor formation

“…Plasma E 2 concentrations of both the WT and ERbKO mice administered E 2 pellets averaged 0.8 nmol/l, which were marginally lower than the peak E 2 concentrations in a premenopausal non-pregnant woman and well below the levels observed in pregnancy (Lenton et al 1982, Lof et al 2009). In non-ovariectomized mice, E 2 concentrations reached peak levels during estrus at around 0.24 nmol/l (Wood et al 2007). Mice not administered E 2 had mean plasma E 2 concentrations of 0.03 and 0.04 nmol/l in the WT and ERbKO groups respectively.…”

Uterine epithelial estrogen receptor α is dispensable for proliferation but essential for complete biological and biochemical responses

“…In the uterus, steroid hormones regulate apoptosis. Circulating levels of E 2 are inversely correlated with apoptosis in uterine luminal and glandular epithelium during the estrous cycle, with the highest level of apoptosis in the epithelium at metestrous as E 2 levels decline (20). Estrogen was shown to suppress apoptosis in the neonatal mouse uterine epithelium via an ERα-dependent induction of apoptosis inhibitory proteins (AIPs) including Birc1a (Baculoviral inhibitors of apoptosis repeat-containing 1) and the inhibition of the activation of the apoptosis executioner, cysteine-aspartic protease-3 (caspase-3) (21).…”

Effect of water decoction of Langsat bark (Lansium domesticum Corr.) on estrous cycle and uterus weight in mice (Mus musculus L.)

“…The estrous phase has high estrogen levels, thus stimulating uterine cells to proliferate and increase the weight of the uterus. 16 If an anti-fertility substance can suppress estrous cycle, it indirectly can also reduce the weight of the uterus. Treatment with water decoction of Langsat's bark had no effect on inducing proliferation, so it did not give a significant effect on uterine weight in mice ( Table 1).…”