Can maternal obesity affect the health of children? Evidence suggests obesity can have detrimental effects on female fertility. The MOBER project investigated whether the disease can even change the ways genes function. Health © Sven Hansche, Shutterstock Obesity is a problem around the world and carries significant health consequences. In Europe, roughly 20-30 % of the population are obese, depending on the country in question. One lesser-known effect of obesity in women is ovarian failure and infertility. Obesity can lead to a breakdown in the endocrine system, which is vital for the production of hormones that regulate many of the body’s core functions. This has detrimental effects on the oocyte (immature female egg cell). Research has shown obesity in pregnant women may also carry effects over to children, predisposing them to obesity, as well as type 2 diabetes. The EU’s MOBER project was launched to investigate the extent to which maternal obesity affects the oocyte. Specifically, how obesity alters its gene expression (how the genes perform their functions), and the epigenetics (how genes are controlled and respond to external factors). The research looked into whether any alterations continue into the early embryo, and even influence the development of the embryo itself. Ultimately, whether a mother’s obesity can affect the health of the child. “The importance is that epigenetic marks could provide a route by which long-term and intergenerational consequences of environment, such as diet, are mediated,” says Gavin Kelsey, Principal Research Scientist in the Epigenetics Programme at the Babraham Institute, and MOBER project coordinator. “The results identify epigenetic changes caused by maternal obesity, so the potential for compromising offspring health and well-being through an epigenetic route, does exist,” Kelsey says. Understanding the epigenetics The research looked into the oocytes from obese female mice. They found the genetic underpinnings to be relatively normal, though the team picked up on some epigenetic alterations. There was greater variability in expressed genes in oocytes from the obese females, for example. To find out exactly what such changes meant, and whether they persisted into the offspring, the researchers carried out in vitro fertilisation of the embryos to an early stage. One of the most important epigenetic changes detected was in methylation levels – essentially, this controls when genes are locked into an ‘off’ position. In some of the oocytes from obese mice, these levels were lower. “The greater variation in gene expression profile in oocytes from the obese group is also an important finding, which could only be revealed by single-cell analysis, and suggests that there is a variable effect on oocyte quality and potential,” says Antonio Galvao, post-doctoral fellow on the MOBER project, working with the support of the Marie Skłodowska-Curie programme. Take-home messages The results from this research and from further studies should let scientists and society better understand the potential harm maternal obesity has on the next generation. “It is important also to realise that there are likely to be other mechanisms that contribute to the intergenerational impact of obesity,” Kelsey notes. Though the research was carried out in mice, there are important lessons for humans to be taken. The most effective current strategy for improving infertility in obese women is control of body weight, explains Galvao. Interventions such as prescribed diets and weight loss management programmes have visible and tangible effects – including improvements in fertility rates. “However, it remains to be seen whether these interventions also correct any epigenetic errors in oocytes, and over what period of weight reversal improvements in oocyte quality occur,” Kelsey explains. Keywords MOBER, obesity, fertility, health, genetic, epigenetics
