Fat-1 Transgene Is Associated With Improved Reproductive Outcomes

High intake of omega-3 polyunsaturated fatty acids (PUFAs) has been associated with a variety of health benefits. However, the role of omega-3 PUFAs in female reproductive function is unclear, with studies showing both positive and negative effects. The type of diet that omega-3 fatty acids are consumed with, for example, a balanced diet vs a high-fat diet (HFD), may influence how omega-3 fatty acids affect female reproductive function. To address the role of omega-3 PUFAs in female reproduction, we used the fat-1 mouse both with and without HFD exposure. Fat-1 mice constitutively express the fat-1 transgene, allowing the conversion of omega-6 to omega-3 fatty acids to yield an optimal tissue ratio of omega-6 to omega-3 fatty acids (similar to 1: 1). In our study, at 15 weeks of age, fat-1 mice had elevated primordial follicles compared with wild-type controls with both standard chow and HFD feeding. Higher serum levels of the omega-3 docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), and eicosapentaenoic acid (EPA) were positively associated with primordial follicle numbers, whereas the ratio of the omega-6 arachidonic acid to EPA + DPA + DHA had the opposite effect. Furthermore, fat-1 mice had increased pregnancy rates and shorter time to pregnancy when fed an HFD compared with wild-type mice. In conclusion, our novel preclinical model suggests that high tissue levels of long-chain omega-3 PUFAs are associated with an improved ovarian reserve and improved reproductive outcomes. Further studies are needed to evaluate omega-3 PUFAs as a potential intervention strategy in women with diminished ovarian reserve.