Abstract
Individuals conceived by in vitro fertilization (IVF) may be at increased risk of cardio-metabolic disorders. We recently reported that IVF conceived male mice displayed impaired glucose metabolism at normal and high body weights. In this study, we examined glucose metabolism in mature female C57BL/6J mice that were conceived by natural conception (NC), by ovarian stimulation (OS) or by IVF following chow or high-fat diet (HFD) for 8 weeks. By design, litter size was comparable between groups, but interestingly the birth weight of IVF and OS females was lower than NC females (p≤0.001). Mature IVF female mice displayed increased fasting glucose as compared to NC and OS mice, irrespective of diet. Mature IVF and OS mice were also more susceptible to the metabolic consequences of high fat diet as compared with NC females, with impaired glucose tolerance (p≤0.01), whereas peripheral insulin resistance and increased hepatic expression of gluconeogenic genes Ppargc1α, Pck1 and G6pc was observed in IVF mice only (p<0.05). This study suggests that ovarian stimulation alone and IVF program distinct metabolic effects in females, but that high fat diet may be required to unmask these effects. This study adds to the growing body of literature that assisted reproduction procedures may increase the risk of developing type 2 diabetes in an obesity prone environment.
Highlights
Adverse prenatal environments are linked to the development of cardiovascular disease and type 2 diabetes in adult human, rodent and sheep offspring [1,2,3,4]
We recently showed that poor fetal growth could be attributed to ovarian stimulation since birth weight was lower in both OS and in vitro fertilization (IVF) groups, but that differences in glucose metabolism were evident solely in mice generated by IVF and not OS alone [18]
We recently showed that IVF young adult humans displayed peripheral insulin resistance [18], an early risk factor in the development of type 2 diabetes [34,35], and significantly greater increases in systolic blood pressure when exposed to a high fat overfeeding diet for 3 days [18]
Summary
Adverse prenatal environments are linked to the development of cardiovascular disease and type 2 diabetes in adult human, rodent and sheep offspring [1,2,3,4]. In vitro fertilization (IVF) exposes the preimplantation embryo to a nonphysiological environment during embryo culture, and has been associated with changes in embryo growth and development in animal models and humans [9,10]. We have recently demonstrated insulin resistance in a small cohort of IVF-conceived young adult men and women, and showed that these individuals were more susceptible to adverse outcomes of short-term high fat overfeeding versus naturally conceived controls [18]. We observed that mature IVF male mice displayed impaired glucose tolerance, under chow and high fat fed conditions [18]
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