The hormonal composition of follicular fluid and its implications for ovarian cancer pathogenesis

Abstract

Ovulation has long been associated with an increased risk in ovarian cancer, yet the underlying molecular mechanisms remain obscure. Two aspects of ovulation have been linked to ovarian cancer pathogenesis. The first is the impact of repetitive tissue injury and repair that occurs with each ovulatory event. The second is the release of follicular fluid that accompanies the follicular rupture and its effect on the ovarian and fallopian tube epithelial cells. Hormones are an important component of follicular fluid, which transiently bathes the ovarian surface and fallopian tube epithelium during ovulation. Much work has been done exploring the role of hormones in fertility, but some, such as estrogen, have also been implicated in the pathogenesis of ovarian and other cancers. Understanding the role of hormones within follicular fluid, as well as how they are altered in disorders which increase ovarian cancer risk, will enhance our ability to assess risk and develop preventative strategies. This review provides an in depth discussion of the logistics of using and studying follicular fluid in ovarian cancer research, and discusses the fluctuations in follicular fluid hormone levels during normal physiological processes versus conditions that increase ovarian cancer risk.

Fimbrial Cells Exposure to Catalytic Iron Mimics Carcinogenic Changes

“…6,34,35 In addition, a model to study follicular fluid effects on fimbria was reported by Bahar-Shany et al, 12 proving the molecular basis and the relative site of ovarian cancer pathogenesis. 36,37 These observations suggest that the carcinogenic pathway originated in the secretory epithelial cells of fimbria, but the molecular mechanism involved is still to be found. Recent studies hypothesize a common oncogenic pathway and similar pathogenetic mechanisms, such as iron-induced oxidative stress derived from retrograde menstruation 7 in epithelial ovarian cancer.…”

Ovarian tumour growth is characterized by mevalonate pathway gene signature in an orthotopic, syngeneic model of epithelial ovarian cancer

“…While the source of this reprogramming is still under investigation, interaction with the hormone- and growth factor-rich ovarian microenvironment is implicated. Recent studies have highlighted the importance of the hormonal environment of the ovary, and follicular fluid in particular, that can induce DNA damage and mutations [4]. …”

Lack of Association between the COMT rs4680 Polymorphism and Ovarian Cancer Risk: Evidence from a Meta-analysis of 3,940 Individuals

“…It has been generally accepted that long-term, excessive exposure to circulating estrogen, which is metabolized to form catechol estrogen, contributes and may be causal to ovarian carcinogenesis. Estrogen is thought to exert its effects in ovarian cancer by enhancing the proliferation of ovarian epithelial cells and increasing their susceptibility to genetic errors during DNA replication (Goodman et al, 2001;Emori and Drapkin, 2014). Accordingly, variations in the genes involved in the biosynthesis and metabolism of estrogen may contribute to altered levels of estrogen and thereby contribute to the risk of ovarian cancer (Holt et al, 2007).…”