Stayner et al. investigated the effect of rapamycin on polycystic kidney disease in utero. Their data showed the potential beneficial effects of rapamycin administered during pregnancy in a rodent model of PKD, while cyst number remains unchanged; the size of the cysts is reduced by rapamycin treatment. Furthermore, they also showed that the inhibition of the mTOR pathway by rapamycin most likely are not mediated via pax2 in their experimental animal model. The result provides evidence of rapamycin may be therapeutically useful for slowing the progression of PKD with a prenatal onset. ABSTRACT: Aim:  Polycystic kidney disease (PKD) in humans encompasses a group of disorders featuring kidney cyst expansion within the first decade (recessive PKD) or beyond the fourth to fifth decade of life (dominant PKD). Autosomal dominant PKD (ADPKD) is caused by mutations in PKD1 or PKD2 genes, and involves cyst formation beginning in utero. Like recessive PKD, ADPKD leads to end-stage kidney disease. Inhibition of mTOR signaling was recently found to halt cyst formation in adult ADPKD mice. In contrast, no studies have investigated potential treatments to prevent cyst formation in utero in recessive PKD. Given that homozygous Pkd1 mutant mice exhibit cyst formation in utero, we decided to investigate whether mTOR inhibition in utero ameliorates kidney cyst formation in fetal Pkd1homozygous mutant mice. Methods:  Pregnant Pkd1(+/-) female mice (mated with Pkd1(+/-) males) were treated with rapamycin from E14.5 to E17.5. Fetal kidneys were dissected, genotyped and evaluated by cyst size as well as expression of the developmental marker, Pax2. Results:  Numerous cysts were present in Pkd1(-/-) kidneys, which were twice the weight of wildtype kidneys. Cyst size was reduced by a third in rapamycin treated Pkd1(-/-) kidney sections and kidney mass was reduced to near wildtype levels. However, some lethality was observed in Pkd1(-/-) null embryos. Moreover, total cyst number was not reduced compared to control embryos. Pax2 expression and kidney development were unaltered in rapamycin treated mice. Conclusion:  Rapamycin treatment reduces cyst formation in utero in Pkd1(-/-) mutant mice, therefore the prevention of kidney cyst expansion in utero by mTOR inhibition is feasible. In contrast, selective rapamycin-associated lethality would likely limit its usefulness as a treatment in utero.