Effects of Histamine Activity and the DAO Enzyme in Pregnancy

Anna Nadal

Physiotherapist and Postgraduate in PNIE

Functions of Histamine in Pregnancy

Histamine serves various functions in allergic and inflammatory processes and neuroendocrine actions in the central nervous system. It is also involved in the menstrual cycle and pregnancy.

The interaction between histamine and female hormones, with their vasodilatory properties, promotes cellular growth and differentiation (Pap, 2004).

An optimal balance between histamine levels and DAO functionality could be crucial for a complication-free pregnancy.

Several studies have linked reduced DAO enzyme activity to multiple pregnancy complications, such as diabetes, the risk of miscarriage, and trophoblastic disorders.

Trophoblastic gestational disease comprises a group of rare conditions where abnormal cells form within the uterus after conception.

However, more research is needed to determine whether women with histamine intolerance experience more complicated pregnancies and higher rates of miscarriage due to disruptions in DAO activity, and if low DAO levels or genetic modifications in the DAO gene could be a prognostic factor for a higher miscarriage risk.

Pregnancy: Histamine Metabolism and the DAO Enzyme

The balance between histamine and the DAO enzyme, which degrades histamine, plays a significant role in an uncomplicated pregnancy (Brew and Sullivan, 2001). A reduction in DAO enzyme activity has been observed in high-risk pregnancies, while normal blood levels have been associated with a favorable fetal development prognosis.

The placenta produces the histamine histidine decarboxylase (HDC) enzyme, which synthesizes histamine, and diamine oxidase (DAO), which degrades histamine.

The diamine oxidase (DAO) enzyme is produced by the placenta in large quantities and acts as a metabolic barrier to prevent excessive bioactive histamine from the placenta entering the circulation of the mother or the fetus.

Therefore, it has been suggested that assessing the functionality of the DAO enzyme may be useful as a tool to detect the risk of pregnancy complications.

The endometrium, the lining of the uterus, and the myometrium, the outer muscular layer of the uterus, contain large numbers of mast cells that contain histamine (Massey et al., 1991; Pap, 2004), and mast cells are also present in the placenta (Purcell and Hanahoe, 1991).

Histamine contributes to embryonic-uterine interactions during implantation.

In the placenta, the expression of the histidine decarboxylase (HDC) enzyme is about 1000 times higher than in other organs (Pap, 2004).

The histidine decarboxylase gene is regulated by progesterone (Paria et al., 1998), which increases during pregnancy.

In humans, H1R receptors have been observed to be expressed in placental villi and play important roles in the exchange of substances between maternal and fetal blood and in the secretion of many hormones such as estrogens (Matsuyama et al., 2004).

Histamine plays a significant role in the fetal-maternal interaction after embryo implantation (Brew and Sullivan, 2001; Pap, 2004, Noskova et al., 2006).

In normal pregnancies, a significant increase in DAO levels has been described during the first trimester (Southren et al., 1964; Dubois et al., 1977), followed by a plateau during the second and third trimesters (Southren et al., 1964; Dubois et al., 1977).

Range of DAO enzyme activity during pregnancy and values related to the risk of pregnancy complications (Southren et al., 1966).

Pregnancies lacking an increase in DAO enzyme activity result in elevated histamine concentrations in plasma and urine, and this excess histamine has been associated with an increased risk of preeclampsia, hyperemesis gravidarum, and miscarriages (Dubois et al., 1977; Clemetson and Cafaro, 1981; Brew and Sullivan, 2006).


  • There is a physiological role of histamine during embryo implantation and fetal development during pregnancy. 
  • A balance is needed between histidine decarboxylase enzymes and DAO enzyme functionality. 
  • Excess histamine can lead to an increased risk of pregnancy complications. 
  • The DAO enzyme serves as a metabolic barrier to prevent excessive histamine entry to the fetus. 
  • A deficiency in DAO enzyme activity has been linked to pregnancy complications. 
  • Assessing DAO enzyme functionality could serve as a diagnostic tool, along with other tests, for assessing the risk of pregnancy complications. 
  • Although more research is needed, effective histamine degradation is important for a healthy pregnancy.

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