PMID- 1585266
OWN - NLM
STAT- MEDLINE
DCOM- 19920612
LR  - 20161123
IS  - 0040-3709 (Print)
IS  - 0040-3709 (Linking)
VI  - 45
IP  - 4
DP  - 1992 Apr
TI  - Embryonic palatal responses to teratogens in serum-free organ culture.
PG  - 369-82
AB  - This study examines development of rat, mouse, and human embryonic palates in 
      submerged, serum-free organ culture. The concentration-response profiles for 
      retinoic acid (RA), triamcinolone (TRI), hydrocortisone (HC), dexamethasone 
      (DEX), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were examined and the 
      mechanisms of clefting in vitro were compared to observed in vivo responses. 
      Craniofacial regions were dissected on gestational day (GD) 12 for mice and GD 14 
      for rat, and cultured for 3-4 days in Bigger's BGJb medium in flasks flushed with 
      50% O2, 45% N2, 5% CO2. Growth and fusion of secondary palates were scored under 
      a dissecting microscope. In serum-free control medium, mouse and rat palatal 
      fusion occurred within the 4-day culture period. Supplementing with fetal bovine 
      serum (FBS) in excess of 1% interfered with growth and fusion in control medium. 
      RA significantly inhibited fusion of mouse and rat palates at 5 x 10(-9) and 1 x 
      10(-10) M, respectively, with RA-induced clefting related to abnormal 
      proliferation and differentiation of medial epithelia. In contrast, 
      glucocorticoid-induced clefting was due to concentration-dependent inhibition of 
      shelf growth. TRI significantly inhibited fusion at 4 x 10(-5) M, and 1 x 10(-4) 
      M DEX or HC, inhibited fusion of 19 and 42% of shelves, respectively. The 
      response rate for DEX in the presence of 1% FBS was increased (42% unfused). TCDD 
      clefting was due to altered medial epithelial differentiation and 1 x 10(-8) M 
      TCDD affected 36% of CD-1 mouse, 23% of C57BL/6N mouse, and 47% of F344 rat 
      palates. When the medium was supplemented with 1% FBS, selenium, transferrin, and 
      additional glutamine, the response of C57BL/6N embryos increased to 75%. This 
      rate is similar to that reported for Trowell's-type cultures with IMEM:F12 medium 
      and 1% FBS. The increased responsiveness to DEX or TCDD in the presence of serum 
      suggests that an unknown factor in serum may be required for full activity. Three 
      human embryonic palatal explants (GD 52 or 53) were cultured for 3-6 days and 
      fused during culture. The present study demonstrates that serum-free organ 
      culture supports development of mouse, rat, and human palatal explants. The 
      present study demonstrates the capacity of this organ culture system to model 
      palatogenesis for several species, and to distinguish between various mechanisms 
      of clefting as presented through selected model compounds. This model should be 
      useful for exploring mechanisms of activity at a cellular and molecular level.
FAU - Abbott, B D
AU  - Abbott BD
AD  - Developmental Toxicology Division, US Environmental Protection Agency, Research 
      Triangle Park, North Carolina 27711.
FAU - Buckalew, A R
AU  - Buckalew AR
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Teratology
JT  - Teratology
JID - 0153257
RN  - 0 (Culture Media)
RN  - 0 (Glucocorticoids)
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 0 (Teratogens)
RN  - 5688UTC01R (Tretinoin)
SB  - IM
MH  - Abnormalities, Drug-Induced/embryology/*pathology
MH  - Animals
MH  - Culture Media
MH  - Glucocorticoids/toxicity
MH  - Humans
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Organ Culture Techniques
MH  - Palate/*abnormalities/drug effects/embryology
MH  - Polychlorinated Dibenzodioxins/toxicity
MH  - Rats
MH  - Rats, Inbred F344
MH  - Teratogens/*toxicity
MH  - Tretinoin/toxicity
EDAT- 1992/04/01 00:00
MHDA- 1992/04/01 00:01
CRDT- 1992/04/01 00:00
PHST- 1992/04/01 00:00 [pubmed]
PHST- 1992/04/01 00:01 [medline]
PHST- 1992/04/01 00:00 [entrez]
AID - 10.1002/tera.1420450408 [doi]
PST - ppublish
SO  - Teratology. 1992 Apr;45(4):369-82. doi: 10.1002/tera.1420450408.