Rm. Ponnamperuma et al., Ovariectomy increases squamous metaplasia of the uterine horns and survival of SENCAR mice fed a vitamin A-deficient diet, AM J CLIN N, 70(4), 1999, pp. 502-508
Background: Retinoic acid is necessary for the growth and differentiation o
f organisms and exerts its molecular actions by binding to specific nuclear
receptors that belong to the thyroid-steroid hormone receptor superfamily.
Steroids and retinoids control the differentiation of the female reproduct
ive epithelia: estrogen maintains the squamous differentiation of vaginal a
nd ectocervical epithelia, whereas retinoic acid maintains the simple colum
nar endocervical and uterine epithelia. These lining epithelia transform in
to a squamous metaplastic phenotype in vitamin A-deficient animals. Further
more, mortality due to vitamin A deficiency is usually attributed to infect
ion resulting in part from dysfunction of the protective epithelia.
Objective: Our objective was to test the hypothesis that estrogen depletion
might change the squamous metaplastic response to vitamin A deficiency and
affect animal survival.
Design: We used female SENCAR mice maintained on a purified vitamin A-defic
ient diet containing either 0 or 3 mu g retinoic acid/g diet. Mice were eit
her ovariectomized or intact. Squamous cells arising in the normally simple
columnar epithelium of the endocervix and uterine cavity were monitored by
keratin 5 expression with immunohistochemistry.
Results: Ovariectomy did not change the time to onset of vitamin A deficien
cy. It increased the number of squamous metaplastic cells and prolonged sur
vival in mice consuming a vitamin A-deficient diet by as much as 40%.
Conclusions: Factors other than epithelial differentiation per se control s
urvival outcome of vitamin A-deficient mice. The results also show a signif
icant increase in longevity of vitamin A-deficient mice when ovariectomized
.