title: Prenatal programming of neuroendocrine reproductive function.
abstract: It is now well recognized that the gestational environment can have long-lasting effects not only on the life span and health span of an individual but also, through potential epigenetic changes, on future generations. This article reviews the "prenatal programming" of the neuroendocrine systems that regulate reproduction, with a specific focus on the lessons learned using ovine models. The review examines the critical roles played by steroids in normal reproductive development before considering the effects of prenatal exposure to exogenous steroid hormones including androgens and estrogens, the effects of maternal nutrition and stress during gestation, and the effects of exogenous chemicals such as alcohol and environment chemicals. In so doing, it becomes evident that, to maximize fitness, the regulation of reproduction has evolved to be responsive to many different internal and external cues and that the GnRH neurosecretory system expresses a degree of plasticity throughout life. During fetal life, however, the system is particularly sensitive to change and at this time, the GnRH neurosecretory system can be "shaped" both to achieve normal sexually differentiated function but also in ways that may adversely affect or even prevent "normal function". The exact mechanisms through which these programmed changes are brought about remain largely uncharacterized but are likely to differ depending on the factor, the timing of exposure to that factor, and the species. It would appear, however, that some afferent systems to the GnRH neurons such as kisspeptin, may be critical in this regard as it would appear to be sensitive to a wide variety of factors that can program reproductive function. Finally, it has been noted that the prenatal programming of neuroendocrine reproductive function can be associated with epigenetic changes, which would suggest that in addition to direct effects on the exposed offspring, prenatal programming could have transgenerational effects on reproductive potential.
authors.affiliation: Institute of Biodiversity Animal Health and Comparative Medicine, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK. Electronic address: Neil.Evans@glasgow.ac.uk.
authors.forename: Neil P
authors.initials: NP
authors.lastname: Evans
authors.affiliation: Institute of Biodiversity Animal Health and Comparative Medicine, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Michelle
authors.initials: M
authors.lastname: Bellingham
authors.affiliation: Institute of Biodiversity Animal Health and Comparative Medicine, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Robinson
mesh_terms: D000818:Animals; D005260:Female; D047109:Fetal Development / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D009490:Neurosecretory Systems / Q000254:growth & development*; D011247:Pregnancy; D039401:Prenatal Nutritional Physiological Phenomena; D012098:Reproduction / Q000502:physiology*; D013312:Stress, Physiological
keywords: Androgen; Environmental chemical; Nutrition; Prenatal programming; Sheep; Stress