PPAR Gamma: Coordinating Metabolic and Immune Contributions to Female Fertility

Abstract

Peroxisome proliferator-activated receptor gamma (PPARG) regulates cellular functions such as adipogenesis and immune cell activation. However, new information has indicated additional roles of PPARG directing the cyclic changes that occur within ovarian tissue of female mammals, including those that facilitate the release of oocytes each estrous cycle. In addition to ovarian PPARG expression and function, many PPARG actions within adipocytes and macrophages have additional direct and indirect implications for ovarian function and female fertility. This encompasses the regulation of lipid uptake and transport, insulin sensitivity, glucose metabolism, and the regulation of inflammatory mediator synthesis and release. This review discusses the developing links between PPARG activity and female reproductive function, and highlights several mechanisms that may facilitate such a relationship.

Figure 1

Overview of PPARG expression by specific ovarian cell types, as follicular development progresses from early antral and preovulatory follicle to postovulatory corpus luteum.

Figure 2

(a) The genomic structure of the $5^{\prime }$ end of the human PPARG gene. Exons 1-6 are common. Exons A1 and A2 are untranslated, and exon B is translated, giving rise to two different proteins corresponding to the G1 or G2 transcripts. (b) The domain structure of PPARG1 and G2 isoforms with the positioning of mutations or polymorphisms resulting in substituted amino acid residues, and altered protein functions. DBD, DNA-binding domain; LBD, Ligand-binding domain. (Figure adapted from Sundvold and Lien[33], Tsai and Maeda [37], and Stumvoll and Häring [38]).

Figure 3

Schematic summarising the developing concept of PPARG influence on ovarian function and female fertility. PPARG is able to strongly influence the activity of ovarian cells directly, in particular steroidogenesis and tissue remodelling. In addition, PPARG can further influence ovarian function via regulation of external metabolic signals and immune cell contributions.