Estrogens and Prolactin Do Not Regulate Maternal and Embryo Iron Homeostasis During Pregnancy

Iron is essential for maternal and fetal health but the mechanisms ensuring increased iron availability during pregnancy are unclear. Hepcidin is the key iron-regulatory hormone and reduces circulating iron levels by preventing iron absorption and mobilization. In healthy human and rodent pregnancies, maternal hepcidin decreases starting in the second trimester to nearly undetectable levels by late pregnancy, which allows for greater iron availability to the fetus. Inappropriately high maternal hepcidin levels during pregnancy results in fetal anemia, intrauterine growth restriction, and potentially fetal death.



Estrogens and prolactin have previously been implicated in baseline hepcidin regulation. As the levels of both hormones increase dramatically over the course of pregnancy, we hypothesized that they may modulate iron homeostasis during pregnancy.  Estrogen and prolactin are required for pregnancy and global knockout (KO) of either estrogen receptor alpha (ER-α) or prolactin receptor (PRLR) results in infertility. Thus, to determine the contribution of estrogens and prolactin on maternal hepcidin suppression during pregnancy we generated mice with liver-specific knockouts of either ER-α (Er-αf/f;Alb-Cre+, ER-α KO) or PRLR (Prlrf/f;Alb-Cre+, PRLR KO).



ER-α KO, PRLR KO and wild-type (WT) females were set up for timed pregnancy and analyzed at E18.5. We observed no change in liver hepcidin mRNA levels in ER-α KO and PRLR KO dams compared to WT dams. ER-α KO, PRLR KO and WT pregnancies also displayed comparable maternal and embryo hematological and iron parameters. These data indicate that estrogens and prolactin do not play a role in maternal hepcidin suppression or iron regulation during pregnancy.