**5. Limitations**

In our study, rodent placental tissue was analyzed in toto. Thus, compartment specific changes might have been masked. We did not analyze circulating Rarres2 levels in maternal or fetal serum. Thus, at this point, our conclusions regarding Rarres1/2 are limited to the placental level only. In line with this limitation, no other local sources of Rarres1/2 (e.g., adipose tissue) were evaluated in our study and only certain gestational time-points were examined. Thus, temporal changes in placental expression profiles remain elusive. The choice to analyze mid-/late-gestational placental tissue was based on our previous findings in human third trimester placentas and trophoblasts [1,2]. Consequently, a potential involvement of Rarres1/2 in placentation and early gestation of our animal models remains to be determined. Furthermore, the use of eNOS−/− as a model for IUGR or preeclampsia has been controversially discussed [70,71]. This model is characterized by impaired endothelial function with uterine artery dysfunction and a lack of blood vessel expansion, as well as a placental transport phenotype [26]. Therefore, eNOS−/− might only represent certain early subtypes of human PE and/or IUGR, which on the other hand may not be relevant to rodents themselves.
