A Decrease in Maternal Iron Levels Is the Predominant Factor Suppressing Hepcidin during Pregnancy in Mice
In order to supply adequate iron during pregnancy, the levels of the iron regulatory hormone hepcidin in the maternal circulation are suppressed, thereby increasing dietary iron absorption and storage iron release. Whether this decrease in maternal hepcidin is caused by changes in factors known to r...
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MDPI AG
2023-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/18/14379 |
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| author | Sheridan L. Helman Sarah J. Wilkins Jennifer C. J. Chan Gunter Hartel Daniel F. Wallace Gregory J. Anderson David M. Frazer |
| author_facet | Sheridan L. Helman Sarah J. Wilkins Jennifer C. J. Chan Gunter Hartel Daniel F. Wallace Gregory J. Anderson David M. Frazer |
| author_sort | Sheridan L. Helman |
| collection | DOAJ |
| description | In order to supply adequate iron during pregnancy, the levels of the iron regulatory hormone hepcidin in the maternal circulation are suppressed, thereby increasing dietary iron absorption and storage iron release. Whether this decrease in maternal hepcidin is caused by changes in factors known to regulate hepcidin expression, or by other unidentified pregnancy factors, is not known. To investigate this, we examined iron parameters during pregnancy in mice. We observed that hepatic iron stores and transferrin saturation, both established regulators of hepcidin production, were decreased in mid and late pregnancy in normal and iron loaded dams, indicating an increase in iron utilization. This can be explained by a significant increase in maternal erythropoiesis, a known suppressor of hepcidin production, by mid-pregnancy, as indicated by an elevation in circulating erythropoietin and an increase in spleen size and splenic iron uptake. Iron utilization increased further in late pregnancy due to elevated fetal iron demand. By increasing maternal iron levels in late gestation, we were able to stimulate the expression of the gene encoding hepcidin, suggesting that the iron status of the mother is the predominant factor influencing hepcidin levels during pregnancy. Our data indicate that pregnancy-induced hepcidin suppression likely occurs because of reductions in maternal iron reserves due to increased iron requirements, which predominantly reflect stimulated erythropoiesis in mid-gestation and increased fetal iron requirements in late gestation, and that there is no need to invoke other factors, including novel pregnancy factor(s), to explain these changes. |
| first_indexed | 2024-03-10T22:39:08Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T22:39:08Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-553dd4aded414848b2f3e278ca70cc7c2023-11-19T11:11:52ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-09-0124181437910.3390/ijms241814379A Decrease in Maternal Iron Levels Is the Predominant Factor Suppressing Hepcidin during Pregnancy in MiceSheridan L. Helman0Sarah J. Wilkins1Jennifer C. J. Chan2Gunter Hartel3Daniel F. Wallace4Gregory J. Anderson5David M. Frazer6Molecular Nutrition Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, AustraliaIron Metabolism Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, AustraliaMolecular Nutrition Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, AustraliaStatistics Unit, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, AustraliaSchool of Biomedical Sciences and Centre for Genomics and Personalised Health, Queensland University of Technology, Kelvin Grove, Brisbane, QLD 4059, AustraliaIron Metabolism Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, AustraliaMolecular Nutrition Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, AustraliaIn order to supply adequate iron during pregnancy, the levels of the iron regulatory hormone hepcidin in the maternal circulation are suppressed, thereby increasing dietary iron absorption and storage iron release. Whether this decrease in maternal hepcidin is caused by changes in factors known to regulate hepcidin expression, or by other unidentified pregnancy factors, is not known. To investigate this, we examined iron parameters during pregnancy in mice. We observed that hepatic iron stores and transferrin saturation, both established regulators of hepcidin production, were decreased in mid and late pregnancy in normal and iron loaded dams, indicating an increase in iron utilization. This can be explained by a significant increase in maternal erythropoiesis, a known suppressor of hepcidin production, by mid-pregnancy, as indicated by an elevation in circulating erythropoietin and an increase in spleen size and splenic iron uptake. Iron utilization increased further in late pregnancy due to elevated fetal iron demand. By increasing maternal iron levels in late gestation, we were able to stimulate the expression of the gene encoding hepcidin, suggesting that the iron status of the mother is the predominant factor influencing hepcidin levels during pregnancy. Our data indicate that pregnancy-induced hepcidin suppression likely occurs because of reductions in maternal iron reserves due to increased iron requirements, which predominantly reflect stimulated erythropoiesis in mid-gestation and increased fetal iron requirements in late gestation, and that there is no need to invoke other factors, including novel pregnancy factor(s), to explain these changes.https://www.mdpi.com/1422-0067/24/18/14379pregnancyiron homeostasishepcidin |
| spellingShingle | Sheridan L. Helman Sarah J. Wilkins Jennifer C. J. Chan Gunter Hartel Daniel F. Wallace Gregory J. Anderson David M. Frazer A Decrease in Maternal Iron Levels Is the Predominant Factor Suppressing Hepcidin during Pregnancy in Mice International Journal of Molecular Sciences pregnancy iron homeostasis hepcidin |
| title | A Decrease in Maternal Iron Levels Is the Predominant Factor Suppressing Hepcidin during Pregnancy in Mice |
| title_full | A Decrease in Maternal Iron Levels Is the Predominant Factor Suppressing Hepcidin during Pregnancy in Mice |
| title_fullStr | A Decrease in Maternal Iron Levels Is the Predominant Factor Suppressing Hepcidin during Pregnancy in Mice |
| title_full_unstemmed | A Decrease in Maternal Iron Levels Is the Predominant Factor Suppressing Hepcidin during Pregnancy in Mice |
| title_short | A Decrease in Maternal Iron Levels Is the Predominant Factor Suppressing Hepcidin during Pregnancy in Mice |
| title_sort | decrease in maternal iron levels is the predominant factor suppressing hepcidin during pregnancy in mice |
| topic | pregnancy iron homeostasis hepcidin |
| url | https://www.mdpi.com/1422-0067/24/18/14379 |
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