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Postnatal Programming and Reproductive Development
The idea, suggested by Charles Stockard in 1921, that there are critical periods during which disruption of the developmental program can have lasting effects on the form and function of tissues, organs and even organisms, is now over 90 years old. Twenty years later, Conrad Waddington coined the term ‘epigenotype’ to describe mechanisms regulating development, and ultimately proposed that cell fate could be determined or programmed by changes in the ‘epigenetic landscape’. The ‘thrifty phenotype hypothesis’, proposed by David Barker in 1990, advanced these ideas, suggesting that development includes programming by the environment in fetal and infant life, and that disruption of development during critical organizational periods can have life-long consequences. Much attention has been focused on identification of critical organizational periods during fetal life. However, it is important to remember that developmental plasticity and, consequently, susceptibility of tissues to developmental disruption does not end at birth but can extend into the postnatal period. Data for laboratory as well as large domestic animals indicate that targeted disruption of steroid hormone-sensitive developmental events during early neonatal life can alter the form and/or function of adult reproductive tract tissues, including the uterus. The uterine gland knockout (UGKO) phenotype, characterized by the absence of endometrial glands in adult sheep, cattle and mice exposed neonatally to steroidal compounds, provides the prototypical example of such programming effects. Factors affecting reproductive development can also be communicated from mother to offspring in first milk (colostrum) via a lactocrine mechanism. In the pig, imposition of a lactocrine-null state by substituting milk replacer for colostrum for two days from birth altered patterns of uterine gene expression and retarded endometrial gland development. Transcriptomic analysis of neonatal uterine gene expression in nursed as compared to replacer-fed gilts on postnatal day 2 revealed over 800 differentially expressed, lactocrine-sensitive genes. A subset of non-coding microRNAs targeting over 100 lactocrine-sensitive uterine transcripts was recently identified, indicating potential for further epigenetic regulation of uterine development. Evidence that minimal colostrum consumption at birth is associated with reduced lifetime fecundity in adult sows supports the idea that lactocrine programming is a factor affecting reproductive efficiency. Data for the mouse indicating lactocrine effects on hippocampal development and memory, and for primates indicating lactocrine effects on offspring temperament and growth support a role for lactocrine regulation of postnatal development. Potential for transgenerational epigenetic effects emphasizes the importance of understanding the biology of postnatal programming and reproductive development.
Keywords: Postnatal programming, Lactocrine effects, Uterus