Ovariectomy increases squamous metaplasia of the uterine horns and survival of SENCAR mice fed a vitamin A-deficient diet

• Published in: The American journal of clinical nutrition Vol. 70; no. 4; pp. 502 - 508
• Main Authors: PONNAMPERUMA, R. M, KIRCHHOF, S. M, TRIFILETTI, L, DE LUCA, L. M
• Format: Conference Proceeding Journal Article
• Language: English
• Published: Bethesda, MD American Society for Clinical Nutrition 01.10.1999; American Society for Clinical Nutrition, Inc
• Subjects: Animals; Biological and medical sciences; Epithelium - pathology; Estrogens; Female; Fundamental and applied biological sciences. Psychology; Hormone metabolism and regulation; Hormones; Immunohistochemistry; Keratins - analysis; Mammalian female genital system; Medical research; Metaplasia; Mice; Mice, Inbred SENCAR; Ovariectomy - adverse effects; Reproductive system; Uterus - pathology; Vertebrates: reproduction; Vitamin A; Vitamin A Deficiency - pathology; Ovariectomy; Rodentia; Vitamin; Estrogen; Uterine horn; Survival; Ovarian hormone; Feeding; Squamous metaplasia; Retinol; Vertebrata; Mammalia; Uterus; Mouse; Surgery; Animal; Female genital system; Sex steroid hormone; Differentiation; Restricted diet
• ISSN: 0002-9165; 1938-3207
• DOI: 10.1093/ajcn/70.4.502

Retinoic acid is necessary for the growth and differentiation of 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 reproductive epithelia: estrogen maintains the squamous differentiation of vaginal and ectocervical epithelia, whereas retinoic acid maintains the simple columnar endocervical and uterine epithelia. These lining epithelia transform into a squamous metaplastic phenotype in vitamin A-deficient animals. Furthermore, mortality due to vitamin A deficiency is usually attributed to infection resulting in part from dysfunction of the protective epithelia. Our objective was to test the hypothesis that estrogen depletion might change the squamous metaplastic response to vitamin A deficiency and affect animal survival. We used female SENCAR mice maintained on a purified vitamin A-deficient diet containing either 0 or 3 microg retinoic acid/g diet. Mice were either 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. Ovariectomy did not change the time to onset of vitamin A deficiency. It increased the number of squamous metaplastic cells and prolonged survival in mice consuming a vitamin A-deficient diet by as much as 40%. Factors other than epithelial differentiation per se control survival outcome of vitamin A-deficient mice. The results also show a significant increase in longevity of vitamin A- deficient mice when ovariectomized.