Title:Inhibition of Topoisomerase I by Anti-Cancer Drug Altered the Endometrial Cyclicity and Receptivity
Volume: 14
Issue: 1
Author(s): K. Liani-Leibson, I. Har-Vardi and E. Priel
Affiliation:
Keywords:
Camptothecin, chemotherapy, DNA-relaxation, endometrium, estrous cycle, topoisomerase I.
Abstract: Topoisomerase I (topo I) is an essential nuclear enzyme involved in virtually all aspects of gene
expression, and is the target of the anti-cancer drugs- camptothecin (CPT) and its derivatives. Improvement of
the survival rates of young women with cancer has led to the consideration of the effects of long-term
chemotherapy on their fertility. The effect of anticancer drugs on ovarian function was previously investigated;
however, no reports are available concerning their effect on the endometrium, whose integrity is an important
factor in embryo implantation. Here we used a rat animal model to investigate the expression and activity of
topo I in the various physiologic phases of the endometrium and the influence of CPT on its integrity and
receptivity.
The results show, for the first time, that the endometrial topo I level and activity are influenced by the
physiologic phases of the endometrium (estrous cycle) and correlate with the estrogen blood concentration.
Treatment with the anti-cancer drug CPT caused histological disruption of the endometrium and deleterious
effect on its cyclicity. Moreover, CPT treatment significantly reduced the implantation rate of embryos,
suggesting alteration in the receptivity of the endometrium.
These results suggest that topo I is important for maintaining the normal physiologic cyclicity and functionality
of the endometrium in rats. Anti-cancer agents that target topo I severely impair estrous cycle progression and
endometrial integrity and receptivity, emphasizing the importance of addressing the effect of chemotherapy on
the endometrial functionality.
