Effect of Folate Deficiency on the Reproductive Organs of Female Rhesus Monkeys: a Cytomorphological and Cytokinetic Study

Abstract

The effect of folate deficiency was studied on the cytomorphology and the kinetics of proliferation of ovarian granulosa cells, and the epithelial cells lining the uterus, cervix and vagina of six sexually mature female rhesus monkeys. The cellular kinetics were studied by in vivo labeling with [3H]thymidine, followed by autoradiography of the histological sections of tissue biopsies taken at various time intervals and labeled mitosis curves. The folate-deficient monkeys showed an increased number of atresic and cystic ovarian follicles with depletion of granulosa cells. There was also a significant impairment of the proliferation kinetics of granulosa cells as indicated by decreased [3H]thymidine labeling index (L.I.), and marked prolongation of the pre-DNA-synthetic time (G1 phase); the DNA-synthetic (S phase) and postsynthetic (G2 phase) periods were only mildly prolonged. These changes may have impaired the ovarian synthesis of the steroidal hormones, estrogen and progesterone. The cervicovaginal epithelium showed megaloblastosis, multinucleation and impairment of orderly proliferaton and maturation. Less pronounced changes were also seen in the uterus. The cytomorphological and functional disturbances in the uterus, cervix and vagina may be partly secondary to those in the ovaries, and partly due to the depletion of their essential folate coenzymes.folate deficiency cytomorphology cytokinetics [3H]thymidine rhesus monkey