Research Description

BIRCWH project title: The Role of PI3K/AKT/NF-κβ Signaling Pathway in High-Fat Diet-Induced Ovarian Dysfunction and Ovarian Aging

Current research focus: I currently focus on investigating the mechanisms behind ovarian dysfunction associated with high-fat diet exposure.

How Dr. Skaznik-Wikiel became interested in this work: During my early scientific career I have developed special interest in studying the effects of different diets and environmental insults on ovarian function and premature ovarian aging. I previously discovered that prolonged exposure to high-fat diet causes diminished ovarian reserve, increased microphage infiltration in the ovary, altered levels of systemic pro-inflammatory and anti-inflammatory cytokines, and subfertility, even in the absence of obesity. Moreover, I established that high-fat diet is associated with downregulation of genes critical to normal ovulatory function. Interestingly, I fund that many repressor genes critical in the inflammatory responses mediated through the PI3K/AKT/NF-κβ signaling pathway are downregulated in mice exposed to high-fat diet, regardless of obesity. The PI3K/AKT/NF-κβ pathway largely depends on NF-κβ mediated transcriptional activation of proinflammatory cytokines, chemokines, and adhesion molecules. A significant knowledge gap exists whether chronic PI3K/AKT/NF-κβ pathway activation occurs in ovaries of individuals eating high-fat diet who do not become obese.

Clinical significance of this research: A high fat intake causes excessive storage of lipid in non-adipose tissue, including the ovary, leading to lipotoxicity, which can affect its physiological function without obesity. Recommended daily intake of fat is 20-35%, however, most American women consume a diet containing 35% fat or more. Analysis of the NHANES data indicates that over 27% of reproductive age women consume diet containing >40% of fat. In addition, high-fat diets are very popular and frequently not associated with obesity. Therefore, understanding the impact of high-fat diet on ovarian function in this group of women has the potential to identify reproductive disturbances typically only considered with obesity. Clarifying the role of high-fat diet in ovarian dysfunction may provide a mechanism for cases of formerly unexplained infertility. 

Relevance of this work to women's health or sex/gender differences: Infertility affects 15% of couples and 30% of cases have no identifiable cause. Treatment options are limited in many cases, even with an implementation of in vitro fertilization. As a reproductive endocrinologist I am truly passionate about women's health and the fact that some day I can apply the findings of my research in clinical practice and improve lives of women and families. Potential outcomes of the current studies could serve as the basis for designing treatments for infertile couples.