Briffa JF1, Cuffe JSM2,3, Hosseini SS1, Tran M1, Moritz KM2, Wlodek ME1
1The University of Melbourne, Parkville, Australia
2University of Queensland, St. Lucia, Australia
3Griffith University, Southport, Australia
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Maternal growth restriction does not exacerbate the reduced placental glucose transporters associated with maternal stress
We have recently demonstrated in a rat model that maternal growth restriction and stress independently impairoffspring metabolic health. As the placenta mediates offspring disease outcomes this study investigated the effects of maternal growth restriction and stress on placental glucose transporters and fetal metabolic parameters.
Uteroplacental insufficiency was induced by bilateral uterine vessel ligation or sham surgery on embryonic day (E) 18 in Wistar-Kyoto rats (F0). F1 females were mated and were allocated to an Unstressed or Stressed pregnancy group. For the Stressed females, physiological measurements (metabolic cage measurements, tail cuff blood pressure,glucose tolerance testing) were performed from mid gestation. At post mortem (E20),plasma (maternal and fetal)and placentae were collected for glucose and insulin concentrations along with placental glucose transporter expression (qPCR) respectively. Fetal pancreata were excised (β-cell determination). Data were analysed by a two-way ANOVA.
Maternal growth restriction reduced F2 fetal weight (-3%), whilst maternal Stress reduced F2 placental weight (-13%). Slc2a1 was reduced in placentae from Unstressed growth restricted mothers (-46%), whereas maternal Stress reduced glucose transporter expression(Slc2a1, Slc2a3, Scl2a4) (-45 to-60%). Maternal Stress tended to reduce maternal insulin concentrations (-9%; P = 0.057) but reduced fetal insulin (-39%),andincreased maternal and fetal glucose (+20%). Interestingly, maternal growth restriction reduced fetal β-cell number (-23%), whilst maternal Stress increased fetal β-cell number (+25%).
We demonstrated that maternal stress, through physiological measurements,increases maternal and fetal glucose concentrations, but reduced placental glucose transporter expression. Reduced Slc2a1 and Slc2a3expression may be a compensatory mechanism to limitfetal glucose transport; however the reduction in Slc2a4 may be maintaining elevated fetal glucose by reducing glucose uptake from the fetus into the placenta. Thesedata highlight that alterations in offspring metabolic health associated with maternal stress exposure in utero may be associated with dysregulated placental glucose handling.