Abstract
Preterm birth (delivery at less than 37 weeks of gestation) is the leading cause of infant mortality worldwide. So far, the application of animal models to understand human birth timing has not substantially revealed mechanisms that could be used to prevent prematurity. However, with amassing data implicating an important role for genetics in the timing of the onset of human labor, the use of modern genomic approaches, such as genome-wide association studies, rare variant analyses using whole-exome or genome sequencing, and family-based designs, holds enormous potential. Although some progress has been made in the search for causative genes and variants associated with preterm birth, the major genetic determinants remain to be identified. Here, we review insights from and limitations of animal models for understanding the physiology of parturition, recent human genetic and genomic studies to identify genes involved in preterm birth, and emerging areas that are likely to be informative in future investigations. Further advances in understanding fundamental mechanisms, and the development of preventative measures, will depend upon the acquisition of greater numbers of carefully phenotyped pregnancies, large-scale informatics approaches combining genomic information with information on environmental exposures, and new conceptual models for studying the interaction between the maternal and fetal genomes to personalize therapies for mothers and infants. Information emerging from these advances will help us to identify new biomarkers for earlier detection of preterm labor, develop more effective therapeutic agents, and/or promote prophylactic measures even before conception.
Highlights
Preterm birth is the leading cause of infant mortality worldwide
The significance of prosta glandins as uterine contractile agonists has been shown in studies of mice with reduced 15-hydroxyprostaglandin dehydrogenase (15-HPGD) - an enzyme responsible for the metabolism of prostaglandin F2α (PGF2α) as well as prostaglandin E2 (PGE2) - the expression of which has been shown to decrease in the chorionic trophoblast of women in labor [22,23,24,25]
Conclusions and future approaches We have summarized recent findings from model organisms that have defined components of birth timing mechanisms for those species, and the evidence for variable maternal and fetal contributions to the process depending upon the species investigated
Summary
Preterm infants born at 36 weeks than those born at 34 weeks [5], infants categorized as late preterm are more likely than their term counterparts to experience diffi culties with feeding, jaundice and respiratory distress [6] (Table 1). Because of the disadvantages of drawing comparisons between the pathophysiology of preterm birth in animal models and humans, coupled with the strong genetic foundation of preterm labor, it may be most effective to use human genetics and genomics to elucidate the mechanisms underlying preterm birth. The study of parturition in sheep is relevant to human birth in that the gestation length and number of offspring per gestation is closer to that of humans than most of the common models in use, the sheer size of pregnant ewes and their fetuses make experimental manipulation easy, and a shift in the site of progesterone production from the corpus luteum of the ovary to the placenta occurs during pregnancy in both women and ewes [16]. In contrast to the human simplex uterus, sheep have a bicornuate uterus, allowing them to maintain one or two fetuses per gestation, and a cotyledonary placenta as opposed to a discoid placenta, as found in primates, indicating that the mechanisms controlling parturition in sheep may be different from
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
