Poster Presentation & Flash Talk 46th Annual Meeting of the Fetal and Neonatal Physiological Society 2019

Sex-specific fetal outcomes in spontaneous intrauterine growth-restricted (spIUGR) guinea pigs following pyrroloquinoline quinone (PQQ) supplementation during pregnancy (#132)

Katherine E Mathers 1 , Paige E Allen 1 , Timothy RH Regnault 1
  1. Obstetrics and Gynaecology and Physiology and Pharmacology and Children’s Health Research Institute, Western University and The Lawson Health Research Institute, London, ONTARIO, Canada

Spontaneous intrauterine growth restriction (spIUGR), a severe complication impacting 8% of human pregnancies, is associated with increased oxidative stress in utero and permanent metabolic changes later in life including impaired liver mitochondrial metabolism. Pyrroloquinoline quinone (PQQ), a natural antioxidant, is linked with increased antioxidant defense and mitochondrial proliferation/function. We predicted that supplementing pregnant guinea pigs with PQQ would improve metabolic outcomes for spIUGR fetuses. PQQ was administered to dams in drinking water (1.5mg/L; n=7) from mid-gestation until 65d (term ~69d). Control animals (n=9) received no PQQ. Fetuses with brain-to-liver ratio >0.65 and body weight <80g were classified as spIUGR (30% of fetuses), and those outside both thresholds classified as normal intrauterine growth (NG). There was no difference in litter size or pregnancy loss rate between PQQ and control groups. Fetal weight and brain-to-liver ratio were negatively correlated, and PQQ-exposed fetuses displayed increased body weight compared to control (p=0.020). Brain, heart, and kidney weights positively correlated with brain-to-liver ratio, while liver weights were negatively correlated. Brain-to-liver ratios were higher in PQQ-exposed female fetuses compared to control (p=0.04), but this effect was not observed in males. Additionally, spIUGR/PQQ females had increased heart weights and decreased kidney and placenta weights compared to spIUGR/control females. PQQ-exposed dams displayed increased liver citrate synthase (CS) and superoxide dismutase (SOD) activity compared to control, indicating increased mitochondrial content and antioxidant capacity. Fetal hepatic mitochondrial ADP-stimulated respiration rates positively correlated with brain-to-liver ratio in control animals but negatively correlated in PQQ-exposed fetuses, suggesting positive PQQ effects for NG individuals but negative effects in IUGR. Our results demonstrate that PQQ administration during pregnancy did not demonstrate any adverse outcomes, but several fetal sex-specific effects, including differences in brain-to-liver ratio, body weight, organ size, and liver mitochondrial function have unknown consequences over life course and warrant further investigation.