The low expression of leukemia inhibitory factor in endometrium: Possible relevant to unexplained infertility with multiple implantation failures

Abstract

Unexplained infertility affects 25% of infertile couples. Cytokines and growth factors have been suggested to play an important role in the initial process of successful implantation in humans and failures in their production may be a cause of unexplained infertility. Leukemia inhibitory factor (LIF) and Interleukin-6 (IL-6) have demonstrated their importance in implantation in both animal and human studies. Lower expression of LIF is found in proliferative phase and maximal expression is found in secretory phase of the menstrual cycle. Lower expression of LIF is also found in secretory phase endometrium in patients with infertility. However, studies investigating whether the levels of LIF in proliferative phase are associated with multiple implantation failures (MIFs) are limited. 30 Endometrial biopsies in proliferative phase from unexplained infertile women with MIF with normal hormone levels were collected. The expression of LIF, IL-6 and its receptor gp130 were measured by immunohistochemistry and western blotting. Moderate expression of LIF in the proliferative phase and high expression of LIF in the secretory phase were found in fertile women. However, lower expression of LIF was found in unexplained infertile women with MIF compared to fertile women. There was no difference in endometrial IL-6 and gp130 expression between unexplained infertile women with MIF and fertile women. LIF expression is independent of the process of embryo and dependent partially on the maternal sex hormone levels. Our data suggest that the initial lower expression of LIF in proliferative phase may be one of the causes for multiple failure of implantation.