title: Sex distribution is a factor in teratogenically induced clefts and in the anti-teratogenic effect of thiamine in mice, but not in genetically determined cleft appearance.
abstract: OBJECTIVE
  Cleft lip and/or palate (CL/P) shows a gender-related distribution in human beings. The reason is unknown. This study analyzed the gender-related cleft appearance with respect to teratogenically and genetically determined cleft appearance and the response to thiamine (vitamin B1) supplementation.
  
  
  METHODS
  Cyclophosphamide (CPA; 0.6 mg) and dexamethasone (0.25 mg) were injected intraperitoneally to A/B-Jena mice on different days of pregnancy. The abortion and malformation rate in the A/B-Jena and A/WySn mice with genetically determined clefting was documented to be gender-specific. Vitamin B1 was given to A/B-Jena dams at different times during pregnancy before, simultaneously and after the teratogenic agent was given to the pregnant mothers. A/WySn mice received oral supplementation at different times during embryonic/fetal development.
  
  
  RESULTS
  There were significantly more living female fetuses when mothers were treated with teratogens, and the embryo lethality and malformation affected more male individuals. However, the survival and malformation rate in A/WySn mice was not gender-specific. Especially in male fetuses, vitamin B1 decreased the teratogenic cleft rate (CPA: p < 0.001, dexamethasone: p = 0.6), whereas there was no effect in the A/WySn mice.
  
  
  CONCLUSIONS
  There was a strong anti-teratogenic effect of vitamin B1, especially in the male fetuses. Genetically determined cleft appearance was not positively influenced. These findings confirm observations about cleft appearance in human beings.
authors.affiliation: Department 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. Electronic address: konstanze.scheller@uk-halle.de.
authors.forename: Konstanze
authors.initials: K
authors.lastname: Scheller
authors.affiliation: Department of Orthodontics, Martin-Luther-University Halle-Wittenberg (Head: Prof. Dr. Dr. R. Fuhrmann), Große Stein Strasse 19, 06108 Halle, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Kalmring
authors.affiliation: Department 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; Petersberg, Halle (Saale), Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Schubert
mesh_terms: D000818:Animals; D002971:Cleft Lip; D002972:Cleft Palate / Q000235:genetics* / Q000517:prevention & control; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011247:Pregnancy; D017678:Sex Distribution; D013723:Teratogens; D013831:Thiamine / Q000494:pharmacology*; D014815:Vitamins / Q000494:pharmacology*
chemical_list: D013723:Teratogens; D014815:Vitamins; D013831:Thiamine
keywords: Gender-specific cleft-appearance; Genetic resistance; Thiamine (vitamin B1) prophylaxis