Improvement of fertility in female mice by a single treatment with telomerase increasing compounds

Abstract

The need for pharmaceutical compounds that improve female fertility is crucial since many women that postpone childbearing today face a decline in their fertility. The essential role of telomerase in female fertility was previously demonstrated and the 4th generation of telomerase knockout mice are infertile. Therefore, increasing telomerase in the ovary may improve fertility by influencing folliculogenesis, oocyte maturation and ovulation processes. We used novel compounds (AGS) that transiently increased telomerase reverse transcriptase (TERT) expression and activity in vitro and in-vivo, to examine their effect on the folliculogenesis and ovulation processes in WT (TERT+/+) and TERT knock out (KO) mice. A single injection of AGS increased telomerase expression and activity in the WT mouse ovary, accelerated oocyte maturation and ovulation and increased the expression of fertility related genes. An increase in the plasma progesterone level and the gonadotropins hormones expression was also observed. The outcome of these enhancements is an increase in the number of embryos and offspring which exhibited a normal development and growth. In TERT KO mice AGS treatment did not affect the mouse ovary stage and the expression of specific genes. These data demonstrate the importance of the transient increase of telomerase in the ovary by pharmaceutical compounds for the improvement of female fertility.