Maternal plasma histamine levels in normal pregnancy are generally similar to those in non-pregnant women during the first trimester, and usually decline gradually during the 2nd and 3rd trimesters (Brew and Sullivan, 2006). In some complications of pregnancy such as hyperemesis gravidarum (HG), spontaneous abortion (SA), pre-term labour (PL) and Pre-eclampsia (PE) histamine levels increase as pregnancy proceeds (Southren et al., 1966; Achari, Achari and Rao, 1971; Beaven et al., 1975), and the elevated levels of histamine may directly cause some of the features of these disorders (Brew and Sullivan, 2006).Placenta is a major source of histamine, but it also releases active diamine amine oxidase (DAO; EC 220.127.116.11) into the maternal circulation, which metabolises histamine (Kapeller-Adler, 1944; Gunther and Glick, 1967; Semeniuchenko, 1975; Granerus, Gillbrand and Wetterqvist, 1977; Purcell and Hanahoe, 1991; Brew, Lakasing and Sullivan, 2007).\u00a0 This breaks down the histamine released from the placenta in normal pregnancy, leading to the limited changes in maternal blood histamine. Clinically, the deported placental DAO activity in maternal blood increases a 1000 fold during normal pregnancy (Southren et al., 1966).The DAO activity rises exponentially in the first 24 weeks of normal gestation and plateaus thereafter to form a normal histamine-DAO-axis (nHDA) (Southren et al., 1966; Beaven et al., 1975; Dubois et al., 1977) (Ahlmark, 1944; Southren et al., 1966; Gunther and Glick, 1967; Weingold and Southren, 1968; Tufvesson, 1978; Beaven et al., 1975; Dubois et al., 1977). In contrast, the spontaneous exponential rise of DAO activity is abrogated from gestational week 8 onwards thus, leading to a defective Histamine-DAO-Axis (dHDA) in pregnancies that present with elevated maternal blood histamine (Southren et al., 1966; Achari, Achari and Rao, 1971; Beaven et al., 1975; Legge and Duff, 1981). Ex-vivo defective Histamine-DAO-Axis also referred to Elevated Histamine Model (EHM) was developed to mimic in vivo dHDA to study effects of histamine in human placenta. The EHM was developed by creating in vitro culture model to represent normal placentae with nHDA and complicated placentae with dHDA. In the nHDA samples, the endogenous DAO activity is maintained to eliminate endogenous production of histamine, while DAO activity is blocked with aminoguanidine in the dHDA samples to allow histamine levels to elevate during the treatment period. Aminoguanidine is a specific inhibitor of DAO enzyme activity (Tamura et al., 1989).