Introduction: Maternal hypoxia is a common perturbation capable of disrupting fetal development. The development of a healthy fetus is dependent upon the formation of a normal placenta which itself may be vulnerable to the effects of maternal hypoxia. This study investigated the effects of maternal hypoxia on fetal growth and placental development.

Methods: Time mated CD1 mice were housed under normoxic conditions (20% oxygen) or exposed to 12% oxygen from embryonic day (E) 14.5 until tissue collection at E18.5.   Fetuses were sexed and fetuses and placentas weighed. Tissue was collected from placentas for analysis of gene and protein expression and histological sections taken for analysis of placental morphology.

Results: Hypoxia reduced fetal weight at E18.5 by approximately 5% (p<0.05) but did not affect placental weight. Vegfa mRNA and protein were not affected by hypoxia but were greater in males compared to females (p<0.05). Placental expression of KDR, the dominant Vegfa receptor, was decreased in placentas of hypoxic dams (p<0.05) and this was associated with impaired vascular development of the placental labyrinth. Hypoxia reduced placental mRNA levels of the mineralocorticoid and glucocorticoid receptors (MR and GR) and reduced the gene and protein expression of the glucocorticoid metabolising enzyme, HSD11B2 (p<0.05).  

Conclusion: Maternal hypoxia induced subtle growth restriction in association with altered placental vascular development. While placentas from male and female fetuses responded similarly to the hypoxic insult, Vegfa was found to be more highly expressed in male placentas. Interestingly, placentas from hypoxic dams were found to have decreased expression of elements pertaining to placental glucocorticoid signalling, indicative of a maternal and/or placental stress response^[1]. Thus, hypoxia may be affecting fetal growth by altering placental formation through multiple mechanisms involving altered placental vasculogenesis and stress.