Creatine metabolism in the uterus: potential implications for reproductive biology

Philip, Mamatha; Snow, Rodney J.; Gatta, Paul A. Della; Bellofiore, Nadia; Ellery, Stacey J.

doi:10.1007/s00726-020-02896-3

Cited by 14 publications

(5 citation statements)

References 48 publications

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“…For example, the creatine pathway is present in human (Castiglione Morelli, et al, 2020 ) and mouse follicular fluid, where it has been demonstrated that mouse follicular fluid creatine concentrations increase around the time of ovulation (Umehara, et al, 2018 ). There is also evidence that the creatine pathway is active in uterine tissue (Philip, et al, 2020 ) during phases of increased energy demand and in the myometrium during pregnancy (Charpigny, et al, 2003 ), thus suggesting that creatine metabolism in the myometrium is likely to be an important factor for the establishment and maintenance of pregnancy as well as contractility during labour. Although there are no previous studies about the effect of this on the cervical epithelium, our results show that the low fertility Suffolk breed had the lowest levels of two important metabolites (N-methylhydantoin and N-carbamoylsarcosine) produced during creatine metabolism.…”

Section: Discussionmentioning

confidence: 99%

Metabolic signature of cervical mucus in ewe breeds with divergent cervical sperm transport: a focus on metabolites involved in amino acid metabolism

et al. 2023

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Introduction Cervical artificial insemination (AI) with frozen-thawed semen in sheep has yielded unacceptably low pregnancy rates. The exception is in Norway where vaginal AI yields non-return rates in excess of 60%, which has been attributed to the ewe breed used. Objectives and methods This study aimed to characterise, for the first time, the ovine follicular phase cervical mucus metabolome, with a focus on the amino acid profile. Cervical mucus was collected from four European ewe breeds with known differences in pregnancy rates following cervical AI with frozen-thawed semen. These were Suffolk (low fertility), Belclare (medium fertility), Norwegian White Sheep (NWS) and Fur (both high fertility). Results A total of 689 metabolites were identified in the cervical mucus of all the four ewe breeds. Of these, 458 metabolites were altered by ewe breed, which had the greatest effect in the dataset (P < 0.05). We detected 194 metabolites involved in the amino acid pathway, of which 133, 56 and 63 were affected by ewe breed, type of cycle and their interaction, respectively (P < 0.05). N-methylhydantoin and N-carbamoylsarcosine (degradation products of creatinine pathway) exhibited the greatest fold change decrease in the Suffolk breed compared to Fur and NWS (P < 0.001). Oxidized metabolites were also decreased in Suffolk compared to high fertility breeds (P < 0.05). In contrast, other metabolites such as 3-indoxyl-sulfate, putrescine, cadaverine were significantly increased in Suffolk at the synchronised cycle. Conclusion The suboptimal amino acid profile in the cervical mucus of the low fertility Suffolk breed may have negative consequences for sperm transport.

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Section: Discussionmentioning

confidence: 99%

Metabolic signature of cervical mucus in ewe breeds with divergent cervical sperm transport: a focus on metabolites involved in amino acid metabolism

et al. 2023

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“…One of the most important metabolites of L-arginine with documented beneficial effects on increased exercise capacity is creatine, which is synthesised mainly in the kidney and in smaller amounts in the liver and pancreas [94]. Creatine plays a key role in muscle energetics [95]. The metabolism of arginine leads to the production of approximately 1-2 g of creatine per day, indicating a need for additional supply from the diet [81].…”

Section: L-arginine and Sportmentioning

confidence: 99%

The Effectiveness of L-arginine in Clinical Conditions Associated with Hypoxia

Kurhaluk

2023

IJMS

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The review summarises the data of the last 50 years on the effectiveness of the amino acid L-arginine in therapeutic practice in conditions accompanied by different-origin hypoxia. The aim of this review was to analyse the literature and our research data on the role of nitric oxide in the modulation of individual physiological reactivity to hypoxia. The review considers the possibility of eliminating methodological conflicts in the case of L-arginine, which can be solved by taking into account individual physiological reactivity (or the hypoxia resistance factor). Considerable attention is paid to genetic and epigenetic mechanisms of adaptation to hypoxia and conditions of adaptation in different models. The article presents data on the clinical effectiveness of L-arginine in cardiovascular system diseases (hypertension, atherosclerosis, coronary heart disease, etc.) and stress disorders associated with these diseases. The review presents a generalised analysis of techniques, data on L-arginine use by athletes, and the ambiguous role of NO in the physiology and pathology of hypoxic states shown via nitric oxide synthesis. Data on the protective effects of adaptation in the formation of individual high reactivity in sportsmen are demonstrated. The review demonstrates a favourable effect of supplementation with L-arginine and its application depending on mitochondrial oxidative phosphorylation processes and biochemical indices in groups of individuals with low and high capacity of adaptation to hypoxia. In individuals with high initial anti-hypoxic reserves, these favourable effects are achieved by the blockade of NO-dependent biosynthesis pathways. Therefore, the methodological tasks of physiological experiments and the therapeutic consequences of treatment should include a component depending on the basic level of physiological reactivity.

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“…Special attention should be paid to the increased Cr demand during pregnancy due to the important role of the PCr/CK system in the uterus and placenta for the maintenance and termination of gestation [34,228,229].…”

Section: Uterus Bb-ck Umtckmentioning

confidence: 99%

Metabolic Basis of Creatine in Health and Disease: A Bioinformatics-Assisted Review

et al. 2021

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Creatine (Cr) is a ubiquitous molecule that is synthesized mainly in the liver, kidneys, and pancreas. Most of the Cr pool is found in tissues with high-energy demands. Cr enters target cells through a specific symporter called Na+/Cl−-dependent Cr transporter (CRT). Once within cells, creatine kinase (CK) catalyzes the reversible transphosphorylation reaction between [Mg2+:ATP4−]2− and Cr to produce phosphocreatine (PCr) and [Mg2+:ADP3−]−. We aimed to perform a comprehensive and bioinformatics-assisted review of the most recent research findings regarding Cr metabolism. Specifically, several public databases, repositories, and bioinformatics tools were utilized for this endeavor. Topics of biological complexity ranging from structural biology to cellular dynamics were addressed herein. In this sense, we sought to address certain pre-specified questions including: (i) What happens when creatine is transported into cells? (ii) How is the CK/PCr system involved in cellular bioenergetics? (iii) How is the CK/PCr system compartmentalized throughout the cell? (iv) What is the role of creatine amongst different tissues? and (v) What is the basis of creatine transport? Under the cellular allostasis paradigm, the CK/PCr system is physiologically essential for life (cell survival, growth, proliferation, differentiation, and migration/motility) by providing an evolutionary advantage for rapid, local, and temporal support of energy- and mechanical-dependent processes. Thus, we suggest the CK/PCr system acts as a dynamic biosensor based on chemo-mechanical energy transduction, which might explain why dysregulation in Cr metabolism contributes to a wide range of diseases besides the mitigating effect that Cr supplementation may have in some of these disease states.

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Creatine metabolism in the uterus: potential implications for reproductive biology

Cited by 14 publications

References 48 publications

Metabolic signature of cervical mucus in ewe breeds with divergent cervical sperm transport: a focus on metabolites involved in amino acid metabolism

Metabolic signature of cervical mucus in ewe breeds with divergent cervical sperm transport: a focus on metabolites involved in amino acid metabolism

The Effectiveness of L-arginine in Clinical Conditions Associated with Hypoxia

Metabolic Basis of Creatine in Health and Disease: A Bioinformatics-Assisted Review

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