Research Anouk Smits

Abstract

Obesity is becoming a global threat, reducing mother's health and reproductive capacities and affecting the offspring's health. Clear preconception care guidelines for obese future mothers are completely lacking. Clinical studies are flawed and more fundamental studies in basic animal models are very scarce. The importance of preconception weight loss on reproduction and baby's health is heavily debated and never been investigated in detail. This research project aims to propose strategically designed animal research models to provide relevant scientific evidence for effective and sustainable preconception care advices to obese women planning for pregnancy. To do so, we will assess the impact of preconception weight loss, diet normalization, increased physical activity, omega-3 rich diet or the combination thereof in obese outbred mother mice on four distinct major outcome parameters: 1) improvement of mother's metabolic profile before conception in relation to the observed weight loss; 2) mother's own fertility success; 3) postnatal health of the offspring and 4) offspring's reproductive physiology. Effective guidelines for preconception care lifestyle interventions in obese patients will drastically lower the (public) health care cost associated with assisted reproduction and should maximally safeguard the health of the baby. The data generated will be the basis for awareness and education programs aiming at improved maternal health at the time of conception.

Researcher(s)

• Promoter: Leroy Jo
• Co-promoter: De Neubourg Diane
• Fellow: Smits Anouk

Research team(s)

• Veterinary physiology and biochemistry

Project type(s)

• Research Project

Abstract

A disturbed maternal metabolism like in obesity or type II diabetes has clearly been associated with disappointing fertility. We extensively showed that such metabolic disorders have direct effects on the micro-environment of the growing and maturing oocyte, ultimately leading to reduced oocyte and embryo quality. Obesity is a global health threatening problem and recent studies indicated that maternal obesity may result in significant health issues in the offspring. More in depth mechanistic research clearly pointed out the importance of uterine programming in early pregnancy. It is not known however whether the metabolic status of obesity as such and/or potential direct effects of the typical fat rich western type diet are responsible for these observations. Based on the epidemiological relevance of obesity and hypercholesterolemia we hypothesize that obesity or an obesogenic diet of the mother around conception or during the entire pregnancy will alter the micro-environment of the growing embryo and fetus. This will change uterine programming ultimately leading to compromised offspring's health and reproductive physiology. To systematically investigate this hypothesis, we will feed female LDLR knock-out mice (LDLR-/-) an obesogenic diet A) several weeks before conception resulting in maternal obesity at conception or B) solely around conception or C) throughout the entire pregnancy. The offspring will be cross-fostered upon birth and will be used to study the general health of the offspring, the ovarian follicular reserve and the process of folliculo- and oogenesis, the offspring's pre-implantation embryo physiology and gene expression pattern and the receptivity of the offspring's uterus to support full pregnancy resulting in healthy offspring. By using this strategic experimental model we will be able to find the most sensitive window during pregnancy for uterine programming of reproduction, and it allows us to study the effects on every specific step on reproductive functioning. We believe that this project proposal may significantly contribute to the concept of "Developmental Origin of Health and Fertility" by further spreading the knowledge that epigenetic effects of maternal metabolism and diet may jeopardize health but also fertility in the offspring.

Researcher(s)

• Promoter: Leroy Jo
• Co-promoter: De Keulenaer Gilles
• Co-promoter: Van Hoeck Veerle
• Fellow: Smits Anouk

Research team(s)

• Veterinary physiology and biochemistry

Project type(s)

• Research Project