Placental Synthesis of Oestriol in Down's Syndrome Pregnancies

Abstract

In the second trimester, oestriol is synthesized in the placenta and secreted into the maternal circulation. 16α-hydroxy dehydroepiandrosterone sulphate (16α-OH-DHEAS) is formed in the fetal liver by hydroxylation of dehydroepiandrosterone sulphate (DHEAS) and transported to the placenta where it undergoes desulphation by steroid sulphatase (STS) and aromatization to oestriol. Maternal serum levels of unconjugated oestriol (UE3) are lower in Down's syndrome pregnancies than in unaffected pregnancies in the second trimester. The underlying cause of this variation was investigated in placenta, fetal liver, maternal serum and amniotic fluid from Down's syndrome pregnancies by measuring the levels of UE3, DHEAS and STS in appropriate tissues and in corresponding samples from unaffected pregnancies. UE3 levels, expressed as multiples of the control median at the appropriate gestation (MOM), were lower in placental tissue (0.52MOM), maternal serum (0.65MOM) and amniotic fluid (0.61MOM) than in unaffected pregnancies. There was a significant correlation between placental and maternal serum levels of UE3 in the Down's syndrome cases. The median STS activity in placental tissue from Down's syndrome pregnancies (1.14MOM) was not significantly different from that of the control pregnancies (1.01MOM), suggesting that placental turnover of the fetal precursor DHEAS is not reduced. However, levels of DHEAS were reduced in maternal serum (0.69MOM), placental tissue (0.54MOM) and fetal liver (0.65MOM) from Down's syndrome pregnancies. Thus, a diminished supply of the fetal precursor DHEAS may be the cause of the decreased placental production of UE3 in Down's syndrome pregnancies in the second trimester.