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      Carbon Monoxide Exposure Does Not Improve The In Vitro Fertilization Rate of Oocytes Obtained from Heterozygous Hmox1 Knockout Mice

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          Abstract

          In our experimental study we explored the impact of maternal reduced heme oxygenase-1 (HO-1) gene ( Hmox1) expression on the in vitro fertilization (IVF) rate through the use of heterozygous Hmox1 knockout mice models ( HET/Hmox1 +/ - ). Also, we hypothesized a beneficial role of gametes exposure during fertilization to carbon monoxide (CO), one of HO-1 by-products, that might be relevant for the improvement of IVF rates. IVF technique was performed by using oocytes obtained from wild-type (WT) or Hmox1 +/ - dams fertilized with WT, Hmox1 +/ - or Hmox1 -/ - mice-derived sperm. The fertilization step occurred either in a conventional incubator (37°C, 5% CO2) or in an incubator implemented with CO (500 ppm). The superovulation yield of WT and Hmox1 +/ - mice and the number of fertilized oocytes was assessed using an optical microscope. The dams’ Hmox1 heterozygous knockout neither impact the superovulation yield, nor did influence the fertilization success rate. Moreover, CO exposure during fertilization could not significantly improve the outcome. Our study showed that the maternal Hmox1 +/ - condition is not affecting the IVF rate in mice. Furthermore, we discovered that CO exposure cannot be exploited to ameliorate this critical step of the IVF protocol.

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          Most cited references21

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          Heme oxygenase 1 is required for mammalian iron reutilization.

          The majority of iron for essential mammalian biological activities such as erythropoiesis is thought to be reutilized from cellular hemoproteins. Here, we generated mice lacking functional heme oxygenase 1 (Hmox1; EC 1.14.99.3), which catabolizes heme to biliverdin, carbon monoxide, and free iron, to assess its participation in iron homeostasis. Hmox1-deficient adult mice developed an anemia associated with abnormally low serum iron levels, yet accumulated hepatic and renal iron that contributed to macromolecular oxidative damage, tissue injury, and chronic inflammation. Our results indicate that Hmox1 has an important recycling role by facilitating the release of iron from hepatic and renal cells, and describe a mouse model of human iron metabolic disorders.
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            Microsatellite polymorphism in heme oxygenase-1 gene promoter is associated with susceptibility to oxidant-induced apoptosis in lymphoblastoid cell lines.

            Heme oxygenase-1 (HO-1) confers cytoprotection against oxidative stress. A (GT)n dinucleotide repeat in the 5'-flanking region of human HO-1 gene shows length polymorphism, which was classified into S ( /= 33 GT). Polymorphism in the HO-1 gene promoter was shown to be associated with susceptibility to pulmonary emphysema and restenosis after angioplasty. However, the biologic mechanism underlying these associations is still unclear. To examine this issue, we established lymphoblastoid cell lines (LCLs) from subjects possessing S/S or L/L genotypes. HO-1 mRNA expressions and HO activities induced by oxidative stress were significantly higher in LCLs with S/S than those with L/L. Furthermore, LCLs with S/S were significantly more resistant to oxidant-induced apoptosis than those with L/L. These findings suggested that the polymorphism of the HO-1 gene is associated with the strength of antiapoptotic effects of HO-1, resulting in an association with susceptibility to oxidative stress-mediated diseases.
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              ART failure: oocyte contributions to unsuccessful fertilization.

              The complexity of fertilization failure during assisted reproductive technologies (ART) is often under-appreciated, as this failure can occur at any number of essential mechanistic and cellular events. Importantly, successful fertilization is heavily dependent upon inherent qualities of the oocytes, and thus reliant upon fidelity of oocyte maturation. Pubmed and medline were searched up to April 2008 for papers on oocyte fertilization and its mechanistic components. References to clinical/human studies were selected wherever possible. Successful oocyte maturation cannot simply be determined via visual assessment of polar body extrusion, but rather entails coordination of numerous cytoplasmic processes not readily observed. Proper regulation of intra-oocyte signaling cascades is crucial for sufficient production and storage of carbohydrates and proteins, successful relocation of organelles and regulation of metabolic pathways required for an apparently mature metaphase II oocyte to complete subsequent fertilization events; such as cumulus penetration, sperm/oocyte binding, fusion, oocyte activation, sperm processing and pronuclear (PN) formation. Regulation of oocyte maturation begins during oocyte growth and is intimately connected with events influencing folliculogenesis. Therefore, the oocyte is subject to a multitude of potential effector impacting fertilization potential and developmental competence long before encountering the artificial environment of the IVF laboratory. Although meticulous care and continued research is essential for future improvement, failure to fertilize and properly form PN following clinical ART is likely to be dependent on historical events in oocyte maturation, not easily explained or prevented through simple modification of contemporary laboratory protocols.
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                Author and article information

                Journal
                Int J Fertil Steril
                Int J Fertil Steril
                Royan Institute
                International Journal of Fertility & Sterility
                Royan Institute
                2008-076X
                2008-0778
                Jan-Mar 2024
                7 November 2023
                : 18
                : 1
                : 76-80
                Affiliations
                [1. ] Department of Environmental Immunology, UFZ-Helmholtz Centre for Environmental Research Leipzig- Halle, Leipzig, Germany
                [2. ] Perinatal Immunology, Saxon Incubator for Clinical Translation (SIKT), Medical Faculty, University Leipzig, Leipzig, Germany
                [3. ] Instituto de Salud y Ambiente del Litoral (ISAL, UNL-CONICET), Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral (UNL), Santa Fe, Argentina
                [4. ] Experimental Obstetrics and Gynecology, Medical Faculty, Otto-von-Guericke University, Magdeburg, Germany
                Author notes
                [* Corresponding Address: ] Department of Environmental Immunology UFZHelmholtz Centre for Environmental Research Leipzig- Halle LeipzigGermany Email: nicole.meyer@ 123456ufz.de
                Article
                Int-J-Fertil-Steril-18-76
                10.22074/IJFS.2023.1982726.1411
                10692744
                38041463
                7e8ec948-65d4-4a6b-9b1e-456382076307
                Any use, distribution, reproduction or abstract of this publication in any medium, with the exception of commercial purposes, is permitted provided the original work is properly cited.

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial 3.0 (CC BY-NC 3.0) License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 13 December 2022
                : 26 April 2023
                : 4 June 2023
                Categories
                Short Communication
                Gynecology and Female Infertility
                Genetics
                Custom metadata
                Romanelli F, Zenclussen L, Zenclussen AC, Meyer N. Carbon monoxide exposure does not improve the in vitro fertilization rate of oocytes obtained from heterozygous Hmox1 knockout mice. Int J Fertil S teril. 2024; 18(1): 76-80. doi: 10.22074/IJFS.2023.1982726.1411 This open-access article has been published under the terms of the Creative Commons Attribution Non-Commercial 3.0 (CC BY-NC 3.0).

                carbon monoxide,gene knockout,ho-1 protein,in vitro fertilization,pregnancy

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