Cellular and molecular basis for endometriosis-associated infertility

Abstract

Endometriosis is a gynecological disease characterized by the presence of endometrial glandular epithelial and stromal cells growing in the extra-uterine environment. The disease afflicts 10%-15% of menstruating women causing debilitating pain and infertility. Endometriosis appears to affect every part of a woman's reproductive system including ovarian function, oocyte quality, embryo development and implantation, uterine function and the endocrine system choreographing the reproductive process and results in infertility or spontaneous pregnancy loss. Current treatments are laden with menopausal-like side effects and many cause cessation or chemical alteration of the reproductive cycle, neither of which is conducive to achieving a pregnancy. However, despite the prevalence, physical and psychological tolls and health care costs, a cure for endometriosis has not yet been found. We hypothesize that endometriosis causes infertility via multifaceted mechanisms that are intricately interwoven thereby contributing to our lack of understanding of this disease process. Identifying and understanding the cellular and molecular mechanisms responsible for endometriosis-associated infertility might help unravel the confounding multiplicities of infertility and provide insights into novel therapeutic approaches and potentially curative treatments for endometriosis.

Fig. 1

Factors associated with reduced fecundity in women with endometriosis

Fig. 2

Mechanisms by which endometriosis affects apoptosis signaling in embryo development (TNF-α tumor necrosis factor-α)

Fig. 3

Potential mechanisms of aberrant DNA methylation in endometriosis (DNMT DNA methyltransferase, HDAC histone deacetylase)

Fig. 4

Methylation dynamics during mammalian folliculogenesis and early mammalian embryo development (blue paternal genome, red maternal genome) adapted from Reik W. et al.,