A Study On The Effects Of Follistatin-like 3 In Early Spontaneous Abortion

BackgroundEarly spontaneous abortion is a common complication in pregnancy.So far,the molecular mechanisms of the disease remain unclear.Follistatin-like 3(FSTL3),an activator antagonist,binds activin A and prevents it from binding to its own receptors,thereby blocking the downstream signaling pathways of activin A.In addition,FSTL3 is an important regulator of activin A in many adult tissues(including pituitary,gonadal,bone and muscle)and tissues differentiation during embryonic development.FSTL3 has a direct regulatory effect on decidualization of women’s endometrium and plays a significant role in the normal reproductive physiological process of mice.Activin A belongs to the transforming growth factor β(TGFβ)superfamily and the over-expressed activin A is found to be associated with reproductive failure in women.According to a literature,activin A increases FSTL3 at both the m RNA and protein levels.Thus,the negative feedback loop between the FSTL3 and activin A can protect cells from accepting excessive activin A.Furthermore,our previous study has evidenced that FSTL3 contributes to the invasion and migration of trophoblast which are critical for a successful pregnancy.ObjectivesThis study aimed to identify the roles of FSTL3 in the establishment and maintenance of pregnancy,and to determine whether FSTL3 is involved in the pathophysiology of early spontaneous abortion.MethodsFSTL3 si RNA was used to silence FSTL3.The trophoblast spheroids mimicking embryos were used in an embryonic adhesion system.The system aimed to investigate the role of FSTL3 silence on embryonic adhesion onto endometrial cell in vitro.The ICR mice models in vivo was used to investigate whether the FSTL3 worked in embryonic implantation.The western blotting was used to explore the interference efficiency and determine the expression of FSTL3 and activin A.Results1、In the in vitro study,silence of FSTL3 in JAR cells significantly reduced the number of trophoblast spheroids adhered onto Ishikawa cells compared with the scramble si RNA(P=0109).2、For the in vivo study,the number of embryos implanted in the uterine horn injected with FSTL3 si RNA mixture was significantly less than that in control group(P<0.001).3、In the case control study,both the expression of FSTL3(P=0.0352)and activin A(P=0.0023)in women with early spontaneous abortion were significantly higher than those in controls.Conclusions1、Silence of FSTL3 influenced the ability of embryonic adhesion and embryonic implantation,suggesting that FSTL3 plays a biological role in the establishment and maintenance of normal pregnancy.2、In the first trimester of pregnancy,the expression levels of FSTL3 and activin A in women with early spontaneous abortion were higher than those in women with normal pregnancy,suggesting that FSTL3 may be involved in the pathology of early spontaneous abortion via neutralizing the elevated activin A.