Overweight and Fertility: What We Can Learn from an Intergenerational Mouse Obesity Model

Abstract

The aim of this study was to evaluate the effects of being overweight on the ability to conceive, fertilization rate, and in vivo development of embryos in regularly cycling, spontaneously ovulating, and naturally mated female mice. The study was based on statistical analysis of data collected during 14 experiments with identical design, performed on 319 control and 327 obese mice, developed in an intergenerational model of obesity induction which eliminates the impact of aging and high-fat feeding. Six-week-old mice with a vaginal sperm plug were slaughtered on embryonic days 2, 3, or 4, and the flushed contents of the oviducts and uteri were assessed by stereomicroscopy. The results showed no association between being overweight and the proportion of ovulating or fertilized females. On the other hand, a strong association was found between being overweight and ovulation yield. On embryonic day 2, significantly higher numbers of eggs were recovered from the oviducts of fertilized obese mice. Maternal overweight status was also associated with higher developmental capacities of preimplantation embryos. In conclusion, contrary to studies based on the high-fat-diet model, in female mice fed regular chow, being overweight was associated with an increased ovulation quota and higher developmental rate of fertilized oocytes. Being overweight did not impact ability to conceive. On the other hand, as documented in our previous studies, the quality of oocytes and blastocysts recovered from overweight mice developed in an intergenerational model of obesity was low.

Lower Plasmatic Levels of Saturated Fatty Acids and a Characteristic Fatty Acid Composition in the Ovary Could Contribute to the High-Fertility Phenotype in Dummerstorf Superfertile Mice

“…The literature describes disaccording opinions about fat content or overweight and lower/higher fertility [ 12 , 35 , 36 , 37 ], which we analyzed in our superior fertile mouse lines. The focus of the present study was to investigate whether the hormonal alterations found in fertility lines can translate into a higher body fat content compared to the control and how it can be connected with their higher ovulation rate.…”

“…The fatty acid panel in the liver analyzed by heatmap and PCA (provided on request) again shows clusters by line, with FL1 revealing the largest differences, including higher OA and a lower AA, DHA, and AA/EPA ratio. As higher levels of SFAs can cause more severe oxidative stress but higher levels of unsaturated FAs cause serious lipid accumulation [ 38 ], this could play a role in their hepatomegaly together with the higher plasma levels of insulin found earlier [ 14 , 35 , 39 ]. Moreover, the FL1 line is the only one with lower fat content in plasma than the control, which could be one of the reasons why it is a healthy mouse line, even showing an enlarged liver.…”