Abstract
Integrins regulate adhesion at the foeto-maternal interface by interacting with secreted phosphoprotein 1 (SPP1) and fibronectin (FN). It is hypothesised that impaired foetal growth of ‘runt’ piglets is linked to altered integrin signalling at the foeto-maternal interface. Placental and endometrial samples associated with the lightest and closest to mean litter weight (CTMLW) (gestational day (GD18, 30, 45, 60 and 90), of both sex (GD30, 45, 60 and 90) (n = 5–8 litters/GD), Large White × Landrace conceptuses or foetuses were obtained. The mRNA expression of the integrin subunits (ITG) ITGA2, ITGAV, ITGB1, ITGB3, ITGB5, ITGB6, ITGB8, SPP1 and FN was quantified by qPCR. Temporal changes in mRNA expression were observed, with different profiles in the two tissues. Endometrial ITGB1 (P ≤ 0.05, GD45) and SPP1 (P ≤ 0.05, all GD combined and GD60) expression was decreased in samples supplying the lightest compared to the CTMLW foetuses. Placentas supplying female foetuses had decreased expression of ITGB6 (GD45, P ≤ 0.05) and FN (GD90, P ≤ 0.05) compared to those supplying male foetuses. Endometrial samples supplying females had increased ITGB3 (P ≤ 0.05, GD60) and FN (P ≤ 0.05, GD30) expression and decreased SPP1 (P ≤ 0.05, GD60) expression compared to male foetuses. Correlations between mean within-gilt mRNA expression and percentage prenatal survival, number of live foetuses or conceptuses and percentage male foetuses were observed. This study has highlighted novel and dynamic associations between foetal size, sex and integrin subunit mRNA expression at the porcine foeto-maternal interface. Further studies should be performed to improve the understanding of the mechanisms behind these novel findings.
Highlights
Low birthweight infants have an increased risk of mortality and morbidity and can be classified as small for gestational age (SGA) or intra-uterine growth restricted (IUGR)
Placental ITGAV expression was influenced by gestational days (GD) (P ≤ 0.05; Fig. 1B), with decreased expression observed at GD60 compared to GD30 and GD45
An overall GD effect was observed in the placental expression of ITGB1 (P ≤ 0.001; Fig. 1C), with increased expression observed at GD45 and GD90 compared to GD30 and GD60
Summary
Low birthweight infants have an increased risk of mortality and morbidity and can be classified as small for gestational age (SGA) or intra-uterine growth restricted (IUGR). The pig has a high incidence of naturally occurring low birthweight piglets, with many litters having a growth-restricted or ‘runt’ piglet that can weigh less than half of the weight of their largest littermates (Widdowson 1971, Ashworth et al 2001, Wu et al 2010). Considering the high prevalence of low birth weight piglets, it is essential to improve the understanding of the mechanisms governing foetal growth. It is hypothesised that inadequate conceptus attachment to the endometrium contributes to the large variation in piglet weight and high prevalence of low birthweight piglets. Integrins (ITGs) are glycoprotein transmembrane receptors which exist as heterodimers composed of noncovalently linked alpha (ITGA) and beta (ITGB) subunits (Giancotti & Ruoslahti 1999). Integrins play a central role in cell adhesion and have been shown to be critical in the
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