Temporal distribution of retinoic acid and cellular retinoic acid-binding protein (CRABP) in the fetal hamster.
The temporal relationship between the distribution of retinoic acid, a known human and rodent teratogen, and that of cellular retinoic acid-binding protein (CRABP) was investigated from Day 11 to Day 14 of hamster prenatal development. The 11,12-(3)H2 and 15(-14C) forms of all-trans-retinoic acid were used for quantitative distribution studies and autoradiography, respectively, and were evaluated 15 min after a single intravenous injection. Radioactivity was detected in all fetal tissues examined (brain, liver, heart, spinal cord, limb, and skin), and at Day 14, approximately 66% of the total radioactivity was present as parent all-trans-retinoic acid. High concentrations of total radioactivity were observed by autoradiography in the midbrain and hindbrain (mesencephalon, metencephalon, and myelencephalon) and spinal cord, but not in the forebrain. At the earliest time studied, limb buds showed relatively high concentrations of radioactivity. Levels of radioactivity were also high in portions of the developing face, nose, and tongue. Immunohistochemical analyses indicated that the amount of CRABP in Day 14 tissues was the highest in spinal cord followed by limb and skin; heart and liver contained only relatively small amounts of this protein. From Day 11 to Day 14, the amount of CRABP, as measured by high-performance size-exclusion liquid chromatography, in the whole body decreased as gestation progressed. Microscopic immunohistochemical localization of CRABP found the highest concentration in the ventral midbrain and in the ventral and lateral sides of the hindbrain and spinal cord; CRABP was also abundant in tongue, limb, and skin. The distribution of CRABP-positive cells in the central nervous system was similar to the distribution of retinoic acid. The data presented here indicate that fetal CRABP appears to play a role in differential accumulation of retinoic acid in certain structures of the developing hamster. The patterns of tissue retinoid and CRABP distribution observed here are consistent with the patterns of congenital malformations induced by prenatal retinoid exposure.
Hatori
A
A
Toxicology Program, Utah State University, Logan 84322.
Shigematsu
A
A
McCormick
A M
AM
Willhite
C C
CC
Sharma
R P
RP
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry; D002352:Carrier Proteins / Q000008:administration & dosage / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D005260:Female; D005333:Fetus / Q000378:metabolism* / Q000502:physiology; D007150:Immunohistochemistry; D007275:Injections, Intravenous; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008431:Maternal-Fetal Exchange / Q000502:physiology; D008647:Mesocricetus / Q000378:metabolism* / Q000502:physiology; D009024:Morphogenesis / Q000502:physiology; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism; D011247:Pregnancy; D018168:Receptors, Retinoic Acid; D012867:Skin / Q000737:chemistry / Q000378:metabolism; D013116:Spinal Cord / Q000737:chemistry / Q000378:metabolism; D014212:Tretinoin / Q000008:administration & dosage / Q000378:metabolism*
D002352:Carrier Proteins; D018168:Receptors, Retinoic Acid; D014212:Tretinoin