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Heme Oxygenases: Novel regulators of reproductive processes

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Pregnancy is a physiological state characterized by the occurrence of different processes taking place at different stages, each of them unique. For pregnancy to occur the uterine tissue needs to be prepared and minimal disturbances can lead to subfertility, e.g. after infections with Chlamydia. Pregnancy ...

Pregnancy is a physiological state characterized by the occurrence of different processes taking place at different stages, each of them unique. For pregnancy to occur the uterine tissue needs to be prepared and minimal disturbances can lead to subfertility, e.g. after infections with Chlamydia. Pregnancy begins with the fertilization of the ovum, followed by implantation of the blastocyst in the maternal uterus. To implant, the blastocyst needs to adhere to the endometrium so that it can be provided with oxygen and nutrients. For these dramatic changes to occur, tissue remodeling and inflammatory processes in the uterus are required. Both, inflammatory and anti-inflammatory pathways are required for this to occur. Heme oxygenases (HO) are ubiquitous enzymes that catalyze the initial and rate limiting steps in the oxidative degradation of heme to bilirubin. HO cleaves a mesocarbon of the heme molecule, producing equimolar quantities of biliverdin, iron, and carbon monoxide (CO). CO and biliverdin, both generated via the catabolism of heme by the isoform HO-1, are potent immunosupressors which induce tolerance against allografted organs.
Recent papers from the literature show that HO-1 emerges as a critical regulator of reproductive processes. It influences uterine receptivity and determines implantation, placentation and intrauterine fetal survival. Its dysregulation was associated to pathologies as spontaneous abortions and pre-eclampsia. Strong evidences from mouse models and translational research point out the importance of HO-1 and its metabolite CO as therapeutic targets for pregnancy-associated disorders.
Because of the rapid progress in the field in the last years, we believe that is very relevant to review the participation of this interesting molecule in pertinent physiologic and pathologic reproductive processes.
We are very excited about the participation of many colleagues in this issue and look forward for interesting discussions. Moreover, we hope that the readers will be interested in this attractive and timely issue.


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