The physiological coordination between the placenta and multiple maternal organs in response to pregnancyhas been recognized as pregnancy adaptation.Preeclampsia,one of the most serious multisystem syndromesthat occurs during pregnancy,exhibits a significant exacerbation of the hypercoagulation status,which reflectsan impaired pregnancy adaptation.The underlying mechanisms are largely unclear.Here we found that thecirculating levels of SerpinF2,the primary physiological inhibitor of plasmin,were substantially higher inpreeclamptic patients than normal controls throughout pregnancy.Transcription analysis revealed that estradioland testosterone could act oppositely to regulate SerpinF2 expression via coordination with FoxAl/A2 in humanrenal cells,where SerpinF2 is principally synthesized.Accordingly,the higher concentrations of testosterone andlower estradiol level were observed in preeclamptic plasma throughout gestation,which at least in part,attributedto the aberrant production and activities of 17 β-HSD3 and aromatase,the essential enzymes for androgen andestrogen synthesis,in the preeclamptic placenta.Pregnant CD-1 mice that were subjected to a testosteronehomolog treatment could mimic preeclampsia-like phenotypes,and exhibited SerpinF2 over production andhypercoagulation status.Taken together,the data deepen our understanding of the pregnancy adaptation of thematernal coagulation system,and provides new insight into the development of preeclampsia from the perspectiveof renal-placental crosstalk.