Maternal Inositol Status and Neural Tube Defects: A Role for the Human Yolk Sac in Embryonic Inositol Delivery?

D'Souza, S W; Copp, Andrew J.; Greene, Nicholas D. E.; Glazier, Jocelyn D.

doi:10.1093/advances/nmaa100

Cited by 30 publications

(49 citation statements)

References 113 publications

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“…On the other hand, during the early weeks of human pregnancy inositol concentration in the embryonic compartment is already significantly higher than in maternal serum [ 83 ]. This suggests that active, carrier-mediated transport mechanisms for inositol are established early in pregnancy and/or there is substantial placental/fetal production of inositol [ 84 ].…”

Section: Evidence-based Effects Of Inositols Supplementation On Human Reproductionmentioning

confidence: 99%

Inositols: From Established Knowledge to Novel Approaches

Dinicola¹,

Unfer²,

Facchinetti

et al. 2021

IJMS

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Myo-inositol (myo-Ins) and D-chiro-inositol (D-chiro-Ins) are natural compounds involved in many biological pathways. Since the discovery of their involvement in endocrine signal transduction, myo-Ins and D-chiro-Ins supplementation has contributed to clinical approaches in ameliorating many gynecological and endocrinological diseases. Currently both myo-Ins and D-chiro-Ins are well-tolerated, effective alternative candidates to the classical insulin sensitizers, and are useful treatments in preventing and treating metabolic and reproductive disorders such as polycystic ovary syndrome (PCOS), gestational diabetes mellitus (GDM), and male fertility disturbances, like sperm abnormalities. Moreover, besides metabolic activity, myo-Ins and D-chiro-Ins deeply influence steroidogenesis, regulating the pools of androgens and estrogens, likely in opposite ways. Given the complexity of inositol-related mechanisms of action, many of their beneficial effects are still under scrutiny. Therefore, continuing research aims to discover new emerging roles and mechanisms that can allow clinicians to tailor inositol therapy and to use it in other medical areas, hitherto unexplored. The present paper outlines the established evidence on inositols and updates on recent research, namely concerning D-chiro-Ins involvement into steroidogenesis. In particular, D-chiro-Ins mediates insulin-induced testosterone biosynthesis from ovarian thecal cells and directly affects synthesis of estrogens by modulating the expression of the aromatase enzyme. Ovaries, as well as other organs and tissues, are characterized by a specific ratio of myo-Ins to D-chiro-Ins, which ensures their healthy state and proper functionality. Altered inositol ratios may account for pathological conditions, causing an imbalance in sex hormones. Such situations usually occur in association with medical conditions, such as PCOS, or as a consequence of some pharmacological treatments. Based on the physiological role of inositols and the pathological implications of altered myo-Ins to D-chiro-Ins ratios, inositol therapy may be designed with two different aims: (1) restoring the inositol physiological ratio; (2) altering the ratio in a controlled way to achieve specific effects.

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Section: Evidence-based Effects Of Inositols Supplementation On Human Reproductionmentioning

confidence: 99%

Inositols: From Established Knowledge to Novel Approaches

Dinicola¹,

Unfer²,

Facchinetti

et al. 2021

IJMS

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“…SLC5A3, encoding SMIT1, is expressed in kidney, brain, placenta, pancreas, heart, skeletal muscle, and lung [100,103]. SLC5A11, encoding SMIT2, exhibits high expression in the small intestine, kidney, heart, skeletal muscle, liver, and placenta, and it is weakly expressed in brain [105,106].…”

Section: Inositol Transporters Alterationsmentioning

confidence: 99%

“…Interestingly, the addition of myo-Ins to the drinking water of mother mice during pregnancy can rescue the survival and viability of the offspring [107][108][109]. However, surviving SLC5A3 knockout mice exhibit myo-Ins depletion in brain, kidney, skeletal muscle, and liver, along with severe abnormalities in peripheral nerves, sciatic nerve and bones [106]. These pleiotropic effects underlined the importance of SMIT1 activity during fetal development and its contribution to fetal myo-Ins levels, although the mechanisms for the impact of altered SMIT1 expression are still under discussion [106].…”

Section: Inositol Transporters Alterationsmentioning

confidence: 99%

Inositols Depletion and Resistance: Principal Mechanisms and Therapeutic Strategies

Lepore¹,

Lauretta

Bianchini

et al. 2021

IJMS

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Inositols are natural molecules involved in several biochemical and metabolic functions in different organs and tissues. The term “inositols” refers to five natural stereoisomers, among which myo-Inositol (myo-Ins) is the most abundant one. Several mechanisms contribute to regulate cellular and tissue homeostasis of myo-Ins levels, including its endogenous synthesis and catabolism, transmembrane transport, intestinal adsorption and renal excretion. Alterations in these mechanisms can lead to a reduction of inositols levels, exposing patient to several pathological conditions, such as Polycystic Ovary Syndrome (PCOS), hypothyroidism, hormonal and metabolic imbalances, like weight gain, hyperinsulinemia, dyslipidemia, and metabolic syndrome. Indeed, myo-Ins is involved in different physiological processes as a key player in signal pathways, including reproductive, hormonal, and metabolic modulation. Genetic mutations in genes codifying for proteins of myo-Ins synthesis and transport, competitive processes with structurally similar molecules, and the administration of specific drugs that cause a central depletion of myo-Ins as a therapeutic outcome, can lead to a reduction of inositols levels. A deeper knowledge of the main mechanisms involved in cellular inositols depletion may add new insights for developing tailored therapeutic approaches and shaping the dosages and the route of administration, with the aim to develop efficacious and safe approaches counteracting inositols depletion-induced pathological events.

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“…21,22 Recently, periconceptional myo-inositol supplementation has been shown to have a role in ameliorating the risk of fetal NTDs, especially in folate-resistant cases. 23 More research with the above micronutrients is needed before a scientific recommendation can be made.…”

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confidence: 99%