Hemochromatosis and pregnancy: iron stores in the Hfe-/- mouse are not reduced by multiple pregnancies

Abstract

Hereditary hemochromatosis (HH), a widespread hereditary iron metabolism disorder, is characterized by an excessive absorption of dietary iron, resulting in increased body iron stores. Some studies indicate a sex difference in disease expression, with women showing a slower disease progression and a less severe clinical profile. This is usually attributed to iron loss during menstruation and pregnancy. However, this link has not been clearly demonstrated. The Hfe-/- mouse model recapitulates key aspects of HH, including an iron overload phenotype similar to that observed in human patients. In this study, we use it to test the impact of multiple pregnancies in the iron stores. One-year-old nulliparous and pluriparous (averaging 29 weaned pups per female) C57BL/6 (B6) and Hfe-/- mice were euthanized, and blood and tissues were collected. Several serological and erythroid parameters were evaluated, as well as tissue nonheme iron content and serum ferritin. Hepcidin 1, hepcidin 2, and bone morphogenetic protein 6 (BMP6) expressions in the liver were determined by real-time PCR. No significant differences were observed for many serological and erythroid parameters although differences occurred in transferrin saturation and mean corpuscular volume in Hfe-/- mice and total iron-binding capacity in B6 mice. Hepatic iron concentration was similar for nulliparous and pluriparous mice of both genotypes, but total iron per organ (liver, spleen, heart, and pancreas) was higher overall in pluriparous females than nulliparous. Hepcidin 1 and 2 and BMP6 expressions were significantly decreased in pluriparous females, when compared with nulliparous, in both genotypes. In conclusion, multiple pregnancies do not reduce body iron stores in Hfe-/- mice.