Mechanisms linking energy balance and reproduction: impact of prenatal environment.

The burgeoning field of metabolic reproduction regulation has been gaining momentum due to highly frequent discoveries of new neuroendocrine factors regulating both energy balance and reproduction. Universally throughout the animal kingdom, energy deficits inhibit the reproductive axis, which demonstrates that reproduction is acutely sensitive to fuel availability. Entrainment of reproductive efforts with energy availability is especially critical for females because they expend large amounts of energy on gestation and lactation. Research has identified an assortment of both central and peripheral factors involved in the metabolic regulation of reproduction. From an evolutionary perspective, these mechanisms likely evolved to optimize reproductive fitness in an environment with an unpredictable food supply and regular bouts of famine. To be effective, however, the mechanisms responsible for the metabolic regulation of reproduction must also retain developmental plasticity to allow organisms to adapt their reproductive strategies to their particular niche. In particular, the prenatal environment has emerged as a critical developmental window for programming the mechanisms responsible for the metabolic control of reproduction. This review will discuss the current knowledge about hormonal and molecular mechanisms that entrain reproduction with prevailing energy availability. In addition, it will provide an evolutionary, human life-history framework to assist in the interpretation of findings on gestational programming of the female reproductive function, with a focus on pubertal timing as an example. Future research should aim to shed light on mechanisms underlying the prenatal modulation of the adaptation to an environment with unstable resources in a way that optimizes reproductive fitness.