Placental Sprouty 2 (SPRY2): Relation to Placental Growth and Maternal Metabolic Status

Abstract

Background:SPROUTY2 (SPRY2) is a membrane-associated protein expressed by placental macrophages with regulatory roles in tissue growth and development. The SPRY2 locus was shown to be associated with body fat distribution and susceptibility to type 2 diabetes. Objectives: We assessed whether SPRY2 mRNA levels are related with maternal metabolic status and with placental weight. We also studied the association of placental mRNA of SPRY2 with macrophage-derived inflammatory genes. Methods: A maternal metabolic profile [C-peptide, post-load glucose and high-molecular-weight (HMW) adiponectin] was assessed between 24 and 28 weeks of gestation in 200 control women delivering adequate-for-gestational-age (AGA) infants. Placentas and newborns were weighed at delivery. Placental mRNA levels of SPRY2 and of macrophage-derived inflammatory genes MMP2, TNFα and CD163 were quantified by real-time PCR. Women delivering small-for-gestational-age infants (SGA, n = 25) and women with gestational diabetes (GDM, n = 25) were also studied as validation groups for placental growth. Results: In control women delivering AGA infants, placental SPRY2 mRNA levels showed positive associations with a more adverse maternal metabolic status (higher maternal C-peptide and post-load glucose and lower HMW adiponectin), with more placental weight and with a more placental inflammatory phenotype (higher placental mRNA levels of MMP2,TNFα and CD163) (all p < 0.05 to p = 0.001). Compared to AGA infants, placental weight and placental SPRY2 mRNA levels were lower in placentas from SGA infants and higher in placentas from women with GDM (all p < 0.0001). Conclusions: Our results suggest a link between placental SPRY2 mRNA levels and placental growth, which may be modulated by maternal metabolic status and placental inflammation.