Hana Manceau1,2, Vincent Puy3, Hervé Puy2,4, Francoise Muller5, Katell Peoc'h6,7, Caroline M Schmitt2,4, Sophie Gil8, Thibaud Lefebvre2,4, Bichr Allaf5, Jonathan Rosenblatt9, Laurent Gouya2,4. 1. Biochimie Clinique, Hôpital Beaujon, APHP, HUPNVS, Clichy, France. 2. UMRs 1149, Centre de Recherche sur l'Inflammation, Institut National de la Santé et de la Recherche Médicale, F-75018, Paris, France. 3. Reproductive Medicine and Medical Cytogenetics Department, Regional University Hospital and School of Medicine, Amiens, France. 4. Centre Français des Porphyries, Hôpital Louis Mourier, APHP, HUPNVS, Colombes, France. 5. Biochimie-Hormonologie, Hôpital Robert Debré, APHP, Paris, France. 6. Biochimie Clinique, Hôpital Beaujon, APHP, HUPNVS, Clichy, France. katell.peoch@aphp.fr. 7. UMRs1139, UFR des Sciences Pharmaceutiques, Université Paris Descartes, Paris, France. katell.peoch@aphp.fr. 8. UMRs1139, UFR des Sciences Pharmaceutiques, Université Paris Descartes, Paris, France. 9. Gynécologie-Obstétrique, Hôpital Robert Debré, APHP, Paris, France.
Abstract
BACKGROUND: Heme is the prosthetic group of numerous proteins involved in vital processes such as oxygen transport, oxidative stress, and energetic mitochondrial metabolism. Free heme also plays a significant role at early stages of development and in cell differentiation processes. The metabolism of heme by the fetal placenta unit is not well-established in humans. METHODS: In a retrospective study, we measured heme precursors in the amniotic fluid (AF) of 51 healthy women, and 10 AF samples from pregnancies with either upper or lower intestinal atresia or ileus were also analyzed. RESULTS: We showed that the porphyrin precursors aminolevulinic acid, porphobilinogen, and protoporphyrin IX are present at the limit of detection in the AF. Total porphyrin levels decreased progressively from week 13 to week 33 (p < 0.01). Interestingly, uroporphyrin, initially detected as traces, increased with maturation, in contrast to coproporphyrin. Uro- and coproporphyrins were type I immature isomers (>90%), suggesting a lack of maturity in the fetal compartment of the heme pathway. Finally, the differential analysis of AF from normal and pathological pregnancies demonstrated the predominant hepatic origin of fetal porphyrins excreted in the AF. CONCLUSION: This study gives the first insight into heme metabolism in the AF during normal and pathological pregnancies.
BACKGROUND:Heme is the prosthetic group of numerous proteins involved in vital processes such as oxygen transport, oxidative stress, and energetic mitochondrial metabolism. Free heme also plays a significant role at early stages of development and in cell differentiation processes. The metabolism of heme by the fetal placenta unit is not well-established in humans. METHODS: In a retrospective study, we measured heme precursors in the amniotic fluid (AF) of 51 healthy women, and 10 AF samples from pregnancies with either upper or lower intestinal atresia or ileus were also analyzed. RESULTS: We showed that the porphyrin precursors aminolevulinic acid, porphobilinogen, and protoporphyrin IX are present at the limit of detection in the AF. Total porphyrin levels decreased progressively from week 13 to week 33 (p < 0.01). Interestingly, uroporphyrin, initially detected as traces, increased with maturation, in contrast to coproporphyrin. Uro- and coproporphyrins were type I immature isomers (>90%), suggesting a lack of maturity in the fetal compartment of the heme pathway. Finally, the differential analysis of AF from normal and pathological pregnancies demonstrated the predominant hepatic origin of fetal porphyrins excreted in the AF. CONCLUSION: This study gives the first insight into heme metabolism in the AF during normal and pathological pregnancies.