Mouse models for the ART of birth

Millions of births across the world have occurred with the aid of assisted reproductive technologies (ARTs), and their use continues to rise globally. This revolution in human reproduction does, however, come with its problems: ART procedures are associated with various issues during pregnancy, including an increased risk of abnormal placentation, preeclampsia and abnormal foetal growth, but the underlying causes remain unclear. Now, Marisa Bartolomei and colleagues use mice to model the effects of four individual ART procedures – hormone stimulation, IVF, embryo culture and embryo transfer – on placental development and foetal growth. All four procedures lead to reduced foetal weight at E12.5 (although embryo transfer and hormone stimulation conditions recovered by E14.5 and E18.5, respectively), and increased placental weight starting at E14.5. ART placentas display abnormalities in the labyrinth vasculature that improve during development, as well as junctional zone overgrowth in late gestation. IVF leads to an increase in levels of sFLT1, an anti-angiogenic factor implicated in preeclampsia. Finally, procedures using embryo culture are associated with defective methylation of imprinting control regions and a general hypomethylation of placental DNA. Thus, ART procedures in mice cause pregnancy complications unrelated to underlying infertility, and techniques using embryo culture have the strongest effects. The authors conclude that efforts should be focused on optimizing embryo culture to ensure healthy outcomes for mothers and offspring.