Key Findings
Estrogen replacement therapy is effective for the treatment of postmenopausal-related conditions such as bone loss, nut is associated with adverse side effects, including coronary events, pulmonary embolism, and breast cancer. The present study was designed to determine if flaxseed (FS) enhances the estrogenic effect of LD on markers of uterine health (i.e., morphology and cell proliferation of luminal epithelia) in the OVX rat model of postmenopausal osteoporosis. Feeding whole ground FS alone, and when combined with LD, did not induce higher cell proliferation compared with the OVX group. The results suggest that FS may not induce uterotrophic effects and that it does not enhance the potential estrogenic effect of LD in OVX rats. Cell proliferation did not differ among the FS, LD, FS + LD, and OVX groups suggesting that FS and LD alone or in combination do not stimulate rapid division of luminal epithelia. Morphological observations in the current study demonstrated estrogen-like effects on the structure of the luminal epithelial cells in animals treated with FS, LD, and FS + LD compared with the OVX group, suggesting that FS, LD, and FS + LD result in some signs of estrogenicity (epithelial cell structure) and not others (PCNA). In conclusion, 10% FS alone and in combination with LD does not affect cell proliferation at the luminal epithelium in the OVX rat model of postmenopausal osteoporosis. The observation that FS alone and combined with LD induces estrogen-like effects on the morphology of the luminal epithelium that are lower in magnitude compared with the SHAM group suggests that FS and LD may not be significant modulators of carcinoma risk in the uterine luminal epithelium.
ABSTRACT
Flaxseed (FS) is an oilseed rich in phytoestrogens and n-3 polyunsaturated fatty acids, compounds that may attenuate bone loss during aging. We previously demonstrated using the ovariectomized (OVX) rat model of postmenopausal osteoporosis that 10% dietary FS combined with low-dose estrogen therapy (LD) preserves vertebral bone mass and strength more so than either treatment alone. However, it was prudent to also consider the effect of this intervention on uterine tissue as LD, and possibly FS, may have estrogenic, and thus negative, effects on uterine tissue. The present study investigated if FS enhances the estrogenic effect of LD on markers of uterine health in OVX rats. Three-month-old rats were randomized to groups: (1) SHAM, (2) OVX, (3) OVX+ FS, (4) OVX+ LD, or (5) OVX+ FS + LD. Ground FS was added to the AIN-93M diet (100 g/kg of diet), and LD was delivered by subcutaneous implant (0.42 lg of 17b-estradiol/kg of body weight/day) to mimic LD in postmenopausal women. After 12 weeks, histological analyses of uterine tissue demonstrated flattened or cuboidal luminal epithelia organized in a single layer in the OVX group, while FS, LD, and FS + LD induced a single layer of elongated luminal epithelia, columnar in shape. The SHAM group had the greatest epithelial mass. Cell proliferation was similar among all OVX groups. Therefore FS and FS +LD similarly induce estrogen-like effects on the morphology of luminal epithelia that are weaker than in the SHAM group without inducing cell proliferation in OVX rats. Thus, FS does not enhance the estrogenic effect of LD on markers of uterine health in OVX rats.
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