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Oral vitamin B1-substitution does not decrease genetically determined cleft rate in mice (A/WySn).

Konstanze Scheller1, Florian Kalmring1, Christian Scheller2

  • 1Department of Oral and Maxillofacial and Facial Plastic Surgery, Martin-Luther-University Halle-Wittenberg (Head: Prof. Dr. Dr. A.W. Eckert), Ernst-Grube-Straße 40, 06120 Halle, Germany.

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Summary
This summary is machine-generated.

High-dose thiamine (vitamin B1) supplementation did not reduce cleft lip and palate (CL/P) in mice. However, the timing of supplementation influenced outcomes, with early administration showing potential benefits for facial fusion.

Keywords:
Genetically resistanceInsufficient uptakeOral thiamine (vitamin B1) supplementation

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Area of Science:

  • Developmental Biology
  • Teratology
  • Nutritional Science

Background:

  • Cleft lip and palate (CL/P) are common congenital birth defects.
  • High-dose vitamin B supplementation has shown promise in reducing teratogenic clefts in animal models and humans.
  • Understanding the role of specific vitamins like thiamine (vitamin B1) is crucial for prevention strategies.

Purpose of the Study:

  • To investigate the effect of thiamine (vitamin B1) on CL/P occurrence in genetically susceptible A/WySn mice.
  • To examine the influence of varying supplementation start times on CL/P development and abortion rates.
  • To analyze thiamine concentrations and receptor expression in relation to CL/P.

Main Methods:

  • Oral supplementation of high-dose thiamine (80 mg/kg) to A/WySn mice at different gestational stages.
  • Analysis of abortion rates and CL/P incidence in offspring.
  • Measurement of thiamine serum and amniotic fluid concentrations via HPLC.
  • Immunochemical analysis of ThTr-1 and ThTr-2 receptors in fetal midface and placenta.

Main Results:

  • High-dose thiamine did not reduce CL/P appearance in A/WySn mice.
  • Supplementation timing influenced CL/P development, with prophylactic/periconceptional timing showing effects.
  • A significant decrease in aborted fetuses was observed across all supplemented groups.
  • Thiamine increased maternal serum levels but not amniotic fluid concentrations; receptor analysis revealed abnormalities in fetuses with clefts.

Conclusions:

  • The timing of thiamine supplementation is critical for embryonic facial and palatal fusion.
  • Prophylactic/periconceptional supplementation, not therapeutic, may be key for preventing CL/P.
  • The study did not achieve a reduction in CL/P rates, and thiamine's local effect in amniotic fluid was not demonstrated in this genetic mouse model.