Gender-dependent differences in the incidence of ochratoxin A-induced neural tube defects in the Pdn/Pdn mouse

• Published in: Congenital anomalies 2010-03, Vol.50 (1), p.29-39
• Main Authors: Ueta, Etsuko, Kodama, Mami, Sumino, Yoshiki, Kurome, Maho, Ohta, Ken-ichi, Katagiri, Ryu-ichi, Naruse, Ichiro
• Format: Article
• Language: English
• Subjects: Animals; Barx1; Female; gender-dependent difference; Gene Expression Regulation, Developmental - drug effects; Gli3; Holoprosencephaly - genetics; Homeodomain Proteins - genetics; Kruppel-Like Transcription Factors - genetics; Male; Mice; Nerve Tissue Proteins - genetics; neural tube defect; Neural Tube Defects - chemically induced; Ochratoxins; Pdn; Polydactyly - genetics; Sex Factors; Sox9; SOX9 Transcription Factor - genetics; Telencephalon - embryology; Transcription Factors - genetics; Zinc Finger Protein Gli3
• ISSN: 0914-3505; 1741-4520
• DOI: 10.1111/j.1741-4520.2009.00255.x

ABSTRACT Genetic polydactyly/arhinencephaly mouse embryo, Pdn/Pdn, exhibits suppression of Gli3 gene expression. Ochratoxin A (OTA) is a teratogen that causes neural tube defects (NTD) in mice. We investigated gender‐dependent differences in the incidence of NTD induced by OTA in the Pdn/Pdn mouse. After administering 2 mg/kg OTA to Pdn/+ female mice, mated with Pdn/+ males, on day 7.5 of gestation, we examined the genotypes, sex and NTD of fetuses on day 18. Non‐treated Pdn/Pdn had a 15.8% risk of NTD, and all NTD fetuses were female. When Pdn/Pdn embryos were exposed to OTA, the incidence of NTD increased to 16 (51.6%) of 31 Pdn/Pdn fetuses, and 10 (71.4%) of 14 male Pdn/Pdn fetuses exhibited NTD. From these results, it was speculated that NTD in OTA‐treated male Pdn/Pdn were due to the synergistic effect between depressed Gli3 and altered sex‐correlated gene expression from OTA treatment. After treatment with OTA, the embryos were recovered on day 9 and gene expressions, which were correlated with Gli3, telencephalic morphogenesis, formation of gonadal anlage, and gender‐dependent differentiation were investigated. From real‐time polymerase chain reaction analysis results, it was suggested that the manifestation of NTD in the male OTA‐treated Pdn/Pdn might be due to the complicated altered gene expressions among Gli3, Wnt7b, Wnt8b, Fez1, Barx1, Lim1, Dmrt1, Igf1, Fog2, Dax1 and Sox9, and in particular, upregulation and gender‐dependent difference in Barx1 and gender‐dependent difference in Sox9 gene expressions might be noteworthy findings.