There is now considerable epidemiological and experimental evidence indicating that early life environmental signals, including nutrition, affect subsequent development. It is now quite clear that a relationship exists between the periconceptional, fetal and early infant phases of life and the subsequent development of chronic diseases including obesity and type 2 diabetes. This relationship, the developmental origins of health and disease (DOHaD), suggests that the embryo/fetus/neonate makes adaptations in response to early life cues, resulting in adjustments in homeostatic systems that are maladaptive in postnatal life, leading to an increased risk of chronic disease and/or the inheritance of risk factors across generations. Reproductive maturation and function is similarly influenced by early life events. This should not be surprising, since the female primordial follicle pool is established early in life and is thus vulnerable to early life events. A multitude of modifying cues inducing developmental adaptations have been identified that result in a decline in ovarian follicular reserve, changes in ovulation rates and altered age at onset of puberty. Both caloric restriction as well as caloric excess induces early life adaptations that produce long-term reproductive dysfunction that may have consequences for future reproductive fitness and may impact subsequent generations. Many pathways have been suggested to underpin these associations, where studies have investigated the maternalfetalplacental relationship as well as events occurring in the early postnatal environment in modulating pubertal onset and ovarian function. But the underlying ovarian mechanisms regulating the relationship between the early life developmental environment and postnatal reproductive dysfunction remain unclear. Thus, it is clear that the perinatal environment provides a potential therapeutic target for intervention and prevention, and focusing on this developmental window of vulnerability may translate into improved interventional strategies for mediating long-term dysfunction.
Funding: DMS is supported by the Canadian Research Chairs Program and by the Canadian Foundation for Innovation.
01 Oct 2015 - 03 Oct 2015