A link between high serum levels of human chorionic gonadotrophin and chorionic expression of its mature functional receptor (LHCGR) in Down's syndrome pregnancies

The incidence of aneuploidy in human pregnancies is unusually high (1–2%) compared to other mammals [1]. Monosomies and trisomies together account for 35% of clinically detected spontaneous abortions (6–20 wks of gestation), stillbirth (4%) and most importantly, are the leading cause of developmental disability and mental retardation of those surviving such pregnancies [2-4]. Of all the genetically compromised pregnancies, Down's syndrome (Trisomy 21, T21) is the most frequent (1/700 live births [5]). The Edward's (Trisomy 18, T18) and Pautau's (Trisomy 13, T13) syndromes are considered relatively rare pregnancy disorders with a prevalence at birth of 1 in 7000 and 29000, respectively [6,7].Genetically, 89–95% of Down's syndrome (DS) patients carry an extra chromosome 21 (chr 21) which arises due to meiotic nondysjunction and is usually inherited from the mother [1]. About 1–2% of DS patients have genetic mosaicism (nondysjunction following fertilisation in early embryos), while 3–4% of cases are due to translocation of chr 21 to another autosome, usually chr 14 [8]. In addition to the characteristic variability in mental retardation, physical and facial features, congenital heart and gastro-intestinal defects, the DS patients are also susceptible to leukaemia and Alzheimer's-like dementia [9-11].The chromosomal abnormalities in DS and other trisomic pregnancies are very often associated with increased or reduced levels of proteins, growth factors and hormones in the maternal blood compared to those of normal pregnancies. For example, in DS pregnancies (11–14 wks of gestation), the serum human chorionic gonadotrophin beta (hCG-β) and pregnancy-associated plasma protein-A (PAPP-A) concentrations tend to be high and low, respectively [12].Human chorionic gonadotrophin (hCG) is the key reproductive hormone regulating human pregnancy. It is a member of the family of glycoprotein hormones that includes luteinizing hormone (LH), follicle stimulating and thyroid stimulatin