Adaptive Response of Estrogen-Iron Axis in Pregnant Purebred Spanish Mares of Different Age

The maintenance of iron (Fe) homeostasis is vital for the physiological function along life. In sexually mature humans and experimental animals, estrogens downregulate hepcidin (Hpc) expression, in order to improve the intestinal absorption and to mobilize Fe stores for maternal erythropoietic expansion and placental development. However, changes of these mechanisms related to regulation of Hpc on the availability of Fe during gestation with advancing age in mares, remain unknown. The objective of this study was to evaluate the interrelationships between serum Fe, Ferritin (Ferr) and Hpc with estrone (E₁) and estradiol-17β (E₂) concentrations in pregnant mares of different ages. Blood samples were taken from 40 pregnant Spanish Purebred mares belonging to four different age groups, 10 subjects for each group: 4 to 6 years, 7 to 9 years, 10 to 12 years, and >12 years were used in this study. Fe concentrations of 4 to 6 and 7 to 9 years groups were higher (P < .01) than 10 to 12 and >12 years groups. Ferr concentrations of 4 to 6 years group were higher (P < .01) than other groups. Hpc concentrations increased and E₁ decreased (P < .01) in >12 years group compared to other age groups. E₂ concentrations of 7 to 9, 10 to 12 and >12 years groups were higher (P < .01) than those of 4 to 6 years group; 7 to 9 years group had higher E₂ concentrations (P < .01) than >12 years group. Fe and Ferr were negatively correlated with Hpc (r = -0.81 and r = -0.67, respectively). E₁ and E₂ were negatively correlated with Fe (r = -0.23 and r = -0.11, respectively). E₂ was positively correlated with Hpc (r = 0.78). In pregnant Spanish Purebred mare, the increase of estrogens, according to the more efficient iron status in response to Hpc inhibition and consequent mobilization of circulating and iron reserve, shows the existence of "estrogen-iron axis" in young mares. Nevertheless, these mechanisms are reversed in old mares, suggesting a less efficient iron metabolism with advancing age. It is hoped that new investigations are needed to understand in depth and clarify further the complex metabolic and hormonal mechanisms involved also in equine species.