| Background:Preeclampsia is a pregnancy-specific disease that occurs after 20 weeks'gestation and complicates 7-12% of all pregnancies worldwide. Preeclampsia is characterized by onset of hypertension, proteinuria and edema; severe preeclampsia could lead to convulsions, coma, heart failure, placental abruption, disseminated intravascular coagulation and HELLP syndrome, even death. Preeclampsia is a leading cause of maternal, fetal and neonatal mortality.Etiology and pathology of preeclampsia remain largely unknown, it is reported that several members of TGF-βsuperfamily and their binding proteins are related to preeclampsia. The activin pathway that contains activin A, inhibin A, follistatin, follistatin-like 3 is one of the hotspots in research field of etiology and pathology of preeclampsia. Activin and inhibin are glycoproteins belonging to the transforming growth factorβ(TGF-β) superfamily; follistatin is a binding protein for TGF-βsuperfamily members and regulates biological activity of its ligand. Several lines of evidence documented a wide range of biological roles for the activins and related proteins in cell growth and differentiation, in regulating embryonic development and in maintaining tissue homeostasis in adult animals. It has been well evidenced that the placental expression and maternal serum levels of activin A and inhibin A are elevated in preeclamptic women. However, the changes in circulating follistatin are controversial. Reports of unchanged and enhanced follistatin in maternal serum were also available.Follistatin-like 3 (FSTL3), also named follistatin-related gene (FLRG), a new member of binding protein for TGF-βsuperfamily members (such as myo statin, activin A, BMPs, GDF-11), it could antagonize their biological function by inhibiting Smad protein mediated intracellular signalling. Follistatin-like 3 is highly expressed in mature testicle and placenta, heart, and pancreatic tissue.Myostatin (MSTN), also called GDF-8, is a relatively new member of TGF-βsuperfamily. Its main biological function is negative regulation for skeletal muscle cell growth, simultaneously myostatin also participate in regulating protein, fat and sugar metabolism. Myostatin is mainly expressed in mammalian skeletal muscle, adipose tissues, placental tissues and trophoblast. It is reported that myostatin propetide, follistatin, follistatin-like 3, ACTRⅡB antagonists and myostatin antibody could inhibit its function.It was recently reported that placental expression of follistatin-like 3 at messenger RNA and protein and maternal serum concentration of follistatin-like 3 were significantly elevated in preeclampsia compared with normal pregnancy. However, the alterations of placental and circulating myostatin, the ligand of follistatin-like 3, in preeclampsia have not been investigated yet.Objective:To detect the serum and placentas levels of follistatin-like 3 and myostatin between preeclamptic and control women; to detect serum levels of follistatin-like 3 and myostatin in the second trimester of pregnancy in women who were destined to develop preeclampsia later; to analyze the alteration and role of follistatin-like 3 and myostatin in the occurrence and development of preeclampsia; to explore the possibility to predict and diagnose preeclampsia by testing the second-trimester serum levels of follistatin-like 3 and myostatin.Methods:Our study included three parts, in the first part we detected serum levels of follistatin-like 3 and myostatin between 40 preeclamptic and 40 normal pregnant women with ELISA; in the second part we detected mRNA and protein levels of the placentas in 40 preeclamptic and 40 normal pregnant women by real-time PCR and Western blotting respectively; in the third part we detected serum levels of follistatin-like 3 and myostatin in 15-20 weeks'gestation in 40 women who were destined to develop preeclampsia later and 40 normal pregnant women.Results:Compared with control group, serum and placental levels of folliatatin-like 3 and myostatin were significantly increased in preeclampsia group (P<0.001 for.both), there was no difference in the severe and mild preeclampsia (P>0.05 for both). Compared with control group, serum level of follistatin-like 3 was significantly lower in 15-20 weeks'gestation in preeclamptic women (P<0.001), however serum level of myostatin was significantly higher in 15-20 weeks'gestation in preeclamptic patients compared with control (P<0.001).Conclusions:The serum and placental expression of follistatin-like 3 and myostatin were elevated in preeclampsia, serum level of follistatin-like 3 in second trimester was decreased and myostatin was increased, it was suggested the complicated role of myostatin and its binding protein, follistatin-like 3, in preeclampsia, the serum level of follistatin-like 3 and myostatin might become potential markers of early prediction and diagnosis for preeclampsia...
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