Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/86479
Type: Thesis
Title: Metabolic phenotyping of young adults and mice born through in vitro fertilization (IVF).
Author: Chen, Miaoxin
Issue Date: 2014
School/Discipline: School of Paediatrics and Reproductive Health
Abstract: In vitro fertilisation (IVF) has been widely used to treat infertility since 1978. Worldwide, there are over 5 million children who have been born following assisted reproduction, mostly by IVF. However, the long term health implications of IVF are unknown. This thesis focuses on the metabolic risks of IVF in adult humans and mouse offspring. A suboptimal in vivo environment during pregnancy, and the early postnatal period, predisposes offspring to chronic diseases later in life. Preimplantation embryos are also sensitive to adverse environmental insults in vivo or in vitro. Emerging evidence suggests that IVF children may be at an increased risk of developing metabolic and cardiovascular diseases. However, it is unclear if increased risk is related to the underlying genetics of the parents, environmental factors, or the treatment procedures per se which include both ovarian stimulation and embryo culture. This is the first study to show that IVF adult humans were insulin resistant, by using gold standard assessment hyperinsulinemic-euglycemic clamp, compared to BMI and aged matched naturally conceived individuals after 3 days of a baseline energy balanced diet (30% fat), and that they tended to be more susceptible to the metabolic consequences of 3 days of high-fat overfeeding (+1250 kcal/day, 45% fat) as evidenced by a greater increase in systolic blood pressure. To separate out potential genetic and environmental confounders as well as the effects of ovarian stimulation versus embryo culture, we developed an IVF mouse model using inbred C57BL/6J mice. Here, we examined glucose metabolism in adult offspring conceived by natural conception (NC), by ovarian stimulation alone (OS) or by IVF, and then fed a chow or high-fat diet (60% fat) for 8 weeks. Our data suggest it is the process of IVF itself that contributes to impaired glucose metabolism in the adult mouse, which was more prominent in males. Moreover, we show that ovarian stimulation impairs fetal growth, and also results in glucose intolerance in offspring, which was unmasked by a high-fat diet in adult females. This study suggests that ovarian stimulation alone and IVF may program distinct metabolic effects in the offspring, but that high fat diet may be required to uncover these differences. Our data shows that the preimplantation period is a critical stage for development and later adult health. The mechanisms underlying these differences are unclear, but may involve epigenetic modifications and/or changes in mitochondrial numbers and function. We initially examined whether altered DNA methylation and expression of key genes PPARGC1A and IGF2 occurs in peripheral insulin sensitive tissues of morbidly obese individuals with or without type 2 diabetes. Our data showed that obese patients with and without type 2 diabetes displayed tissue specific DNA methylation of PPARGC1A and IGF2, highlighting the importance of measuring individual tissues in this response in humans and controlling for adiposity. Whether these alternations are evident in IVF conceived adults requires further study. In conclusion, this study highlights an increased risk of developing type 2 diabetes and cardiovascular disease in IVF offspring later in life in an obesogenic environment.
Advisor: Heilbronn, Leonie Kaye
Robker, Rebecca Louise
Norman, Robert John
Dissertation Note: Thesis (Ph.D.) -- University of Adelaide, School of Paediatrics and Reproductive Health, 2014
Keywords: In Vitro Fertilisation (IVF); ovarian stimulation; embryo culture; high fat diet; glucose metabolism; developmental origins of health and disease
Provenance: This electronic version is made publicly available by the University of Adelaide in accordance with its open access policy for student theses. Copyright in this thesis remains with the author. This thesis may incorporate third party material which has been used by the author pursuant to Fair Dealing exceptions. If you are the owner of any included third party copyright material you wish to be removed from this electronic version, please complete the take down form located at: http://www.adelaide.edu.au/legals
Appears in Collections:Research Theses

Files in This Item:
File Description SizeFormat 
01front.pdf275.29 kBAdobe PDFView/Open
02whole.pdf3.55 MBAdobe PDFView/Open
Permissions
  Restricted Access
Library staff access only925.17 kBAdobe PDFView/Open
Restricted
  Restricted Access
Library staff access only3.36 MBAdobe PDFView/Open


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.