Spontaneous premature birth as a target of genomic research

Abstract

Spontaneous preterm birth is a serious and common pregnancy complication associated with hormonal dysregulation, infection, inflammation, immunity, rupture of fetal membranes, stress, bleeding, and uterine distention. Heredity is 25-40% and mostly involves the maternal genome, with contribution of the fetal genome. Significant discoveries of candidate genes by genome-wide studies and confirmation in independent replicate populations serve as signposts for further research. The main task is to define the candidate genes, their roles, localization, regulation and the associated pathways that influence the onset of human labor. Genomic research has identified some candidate genes that involve growth, differentiation, endocrine function, immunity and other defense functions. For example, selenocysteine-specific elongation factor (EEFSEC) influences synthesis of selenoproteins. WNT4 regulates decidualization, while a heat-shock protein family A (HSP70) member 1 like, HSPAIL, influences expression of glucocorticoid receptor and WNT4. Programming of pregnancy duration starts before pregnancy and during placentation. Future goals are to understand the interactive regulation of the pathways in order to define the clocks that influence the risk of prematurity and the duration of pregnancy. Premature birth has a great impact on the duration and the quality of life. Intensification of focused research on causes, prediction and prevention of prematurity is justified.Abbreviations: CA, chorioamnionitis; CRH, corticotropin-releasing hormone; DHEA, dehydroepiandrosterone; GWAS, genome-wide association study; P4, progesterone; PR, progesterone receptor; PTB, preterm live birth; PPROM, preterm prelabor rupture of fetal membranes; Sec, Selenocysteine; SNV, single nucleotide variant; SPTB, spontaneous preterm live birth; SPTD, spontaneous preterm labor and delivery of live infant; WES, whole exome sequencing; WGS, whole genome sequencing

Integrative genetic, genomic and transcriptomic analysis of heat shock protein and nuclear hormone receptor gene associations with spontaneous preterm birth

“…Thus, varying pathways leading to SPTB could partly explain the variations in the results among the datasets. Maternal, and also to some extent fetal, genomes affect the susceptibility to preterm birth and duration of pregnancy in general 23 , 47 , 48 . We analyzed several maternal and fetal GWAS and WES datasets to identify HSP and NR genes associated with preterm birth.…”

“…We used multiple available sources of preterm birth GWAS data, including both maternal and fetal genomes. The first dataset we used comprised 43,568 mothers of European ancestry; these mothers were identified from among 23andMe’s research participants as described previously 48 . The second dataset included meta-analysis data for 4632 mothers and their 1960 infants from three independent Nordic (Finnish, Danish, and Norwegian) preterm birth case/control data sets of European ancestry 31 .…”

Pluripotent stem cell-derived endometrial stromal fibroblasts in a cyclic, hormone-responsive, coculture model of human decidua

“…We expect that our model will facilitate mechanistic studies of reproductive-disease-related genes as identified by animal models and, importantly, human genome-wide association studies (GWASs) and gene regulatory mapping studies (Hallman et al, 2019;Zondervan et al, 2016;Sakabe et al, 2020). For example, recent studies have reported that a novel causal locus and candidate gene, HAND2, is associated with gestational length (Sakabe et al, 2020).…”

The Combined Effects of Fine Particulate Matter and Temperature on Preterm Birth in Seoul, 2010–2016

“…The recent increase in environmental pollution, which is associated with high PM concentrations, has been shown to have negative effects on maternal immunity and neonatal health [11]. PM exposure may induce reproductive toxicity mediated by placental DNA methylation and maternal inflammatory responses, suggesting a link between PM exposure and preterm birth risk [12].…”