Fat-1 Transgene Is Associated With Improved Reproductive Outcomes

• Published in: Endocrinology (Philadelphia) 2018-12, Vol.159 (12), p.3981-3992
• Main Authors: Hohos, Natalie M, Cho, Kirstin J, Swindle, Delaney C, Allshouse, Amanda A, Rudolph, Michael C, Skaznik-Wikiel, Malgorzata E
• Format: Article
• Language: English
• Subjects: Animals; Arachidonic Acid - blood; Diet, High-Fat; Docosahexaenoic Acids - blood; Eicosapentaenoic Acid - analogs & derivatives; Eicosapentaenoic Acid - blood; Fatty Acids, Omega-3 - blood; Fatty Acids, Omega-3 - metabolism; Fatty Acids, Omega-6 - blood; Fatty Acids, Unsaturated - blood; Female; Fertility - genetics; Lipid Metabolism - genetics; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Pregnancy; Reproduction - genetics; Transgenes - physiology
• ISSN: 1945-7170; 0013-7227; 1945-7170
• DOI: 10.1210/en.2018-00723

High intake of ω-3 polyunsaturated fatty acids (PUFAs) has been associated with a variety of health benefits. However, the role of ω-3 PUFAs in female reproductive function is unclear, with studies showing both positive and negative effects. The type of diet that ω-3 fatty acids are consumed with, for example, a balanced diet vs a high-fat diet (HFD), may influence how ω-3 fatty acids affect female reproductive function. To address the role of ω-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 ω-6 to ω-3 fatty acids to yield an optimal tissue ratio of ω-6 to ω-3 fatty acids (∼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 ω-3 docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), and eicosapentaenoic acid (EPA) were positively associated with primordial follicle numbers, whereas the ratio of the ω-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 ω-3 PUFAs are associated with an improved ovarian reserve and improved reproductive outcomes. Further studies are needed to evaluate ω-3 PUFAs as a potential intervention strategy in women with diminished ovarian reserve.