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

Roshini M. Ponnamperuma, Susan M. Kirchhof, Lisa Trifiletti, Luigi M. De Luca

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Background: 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. 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-deficient diet containing either 0 or 3 μg 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. Results: 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%. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)502-508
Number of pages7
JournalAmerican Journal of Clinical Nutrition
Issue number4
StatePublished - Oct 1999
Externally publishedYes


  • Differentiation
  • Estrogen
  • Female reproductive epithelium
  • Mice
  • Ovariectomy
  • Retinoic acid
  • Survival
  • Vitamin A deficiency

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics


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