Prolonged maternal hypoxia in mid-late gestation causes growth restriction and reduced nephron number in the mouse offspring — ASN Events
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Prolonged maternal hypoxia in mid-late gestation causes growth restriction and reduced nephron number in the mouse offspring (#374)

Sarah L Walton 1 , Reetu R Singh 1 , Calida Neal 2 , Lorine Wilkinson 2 , Melissa H Little 2 , Karen M Moritz 1
  1. The University of Queensland, St Lucia, QLD, Australia
  2. Institute of Molecular Biosciences, St Lucia, QLD, Australia

Acute or chronic bouts of unexpected under-oxygenation can be damaging to fetal development depending on both the timing and severity of hypoxic insult. This may lead to adult onset diseases. This study investigated whether mid-late gestational hypoxia affects growth outcomes, kidney structure and function of mouse offspring. Pregnant CD-1 mice at embryonic day (e) 14.5 were placed in a hypoxia chamber at 12% oxygen (n=11) until naturally littering-down or were kept in control conditions (21% oxygen; n=11). Offspring body weights were recorded at postnatal day 1 (P1) until P21. At P21 offspring were culled and kidneys dissected out, weighed and fixed in 4% PFA for determination of glomerular number. Renal function was assessed in 10-week-old animals via 24h metabolic cage collections. Urinary sodium, chloride and potassium concentrations were measured using a COBAS Integra 400+.
Offspring from hypoxic dams were significantly lighter than controls at birth (P=0.009) and remained lighter until P21 (Ptreatment=0.0002). Absolute kidney weights were reduced in male and female offspring of hypoxic dams (P=0.04) compared ¬to controls. Urine output over 24 hours (corrected for body weight) and water intake was not different between treatment groups or sexes. Food intake over 24 hours was not different between treatment groups however females consumed significantly more food than males (Psex=0.01). Urinary composition did not differ between treatment groups. Preliminary analysis showed a tendency for reduced glomerular number in male offspring of hypoxic dams compared to controls at P21 (P = 0.09). ¬Maternally induced hypoxia during mid-late gestation in the mouse significantly altered fetal development as indicated by reduced body weights at P1. No catch-up growth was observed, as hypoxic offspring remained lighter until P21. A reduced glomerular number in male offspring implies that kidney development has also been affected. However, this reduction in glomerular number does not appear to have altered renal function in young animals.