Short-term hypoxia in mid-gestation causes growth restriction and reduces nephron number in the mouse offspring (#369)
Introduction: Hypoxia is an insult the fetus may experience during maternal anemia, asthma, smoking, umbilical cord occlusion and placental insufficiency. This study investigated whether a short period of hypoxia during mid-gestation has detrimental effects on kidney development and growth of the fetus.
Methods: Pregnant CD-1 mice at embryonic day (e) 12.5 were placed in a hypoxia chamber at 12.5% oxygen (Hypoxia group, N=11) for 48 hours or were kept in control conditions (21% oxygen, N=11). Some dams (Hypoxia, N=5, control, N=4) were sacrificed at E14.5 and embryonic kidneys collected. The remaining dams littered-down naturally (Hypoxia, N=6, Control, N=7) and offspring weights recorded from postnatal day 2 (P2) to P15. At P15 male and female sacrificed and kidneys excised for examination of glomerular number (Embryonic kidneys; control: N-8, hypoxia: N=10, P15 kidneys; control; males: N=9, females: N=6, hypoxia: males: N=8, females: N= 6).
Results: Glomerular number was significantly reduced in hypoxic embryonic E14.5 kidneys compared to controls (P<0.0001). At P2, offspring of hypoxic dams were significantly lighter (P=0.02) and remained lighter until P15 compared to controls. Nephron number at P15 was significantly reduced in offspring following prenatal hypoxia compared to control (Ptreatment<0.0001, Psex=0.08, 28% in males, 24% in females).
Conclusion: Hypoxic period during mid-gestation significantly alters kidney development resulting in a reduced nephron number. Interestingly, the kidneys do not appear to recover from this insult as nephron number is reduced to a similar degree in postnatal life as well, suggesting that the effects of hypoxia on the developing kidney are permanent. Furthermore, this short period of hypoxia caused significant growth restriction and in conjunction with the offspring’s nephron deficit may increase their predisposition to future cardiovascular and renal diseases and this needs further investigation in this model.