Abstract
We studied the structural changes in the enamel of mandibular third molars of miniature pigs administered a daily oral dose of 2 mg NaF (approximately 0.9 mg of fluoride) per kg body weight (added to the feed) for 1 year. The treatment period covered most of the secretory stage and the entire post-secretory stage of amelogenesis of the M3. The enamel of the molars from the fluoride-fed pigs appeared opaque and chalky, and the erupted portions were stained brown. The underlying histopathological change was a pronounced subsurface hypomineralization of the enamel beneath a thin surface rim of higher mineral content. This enamel hypomineralization was attributed to a fluoride-induced impairment of the process of enamel maturation. The most conspicuous finding in the fluorotic enamel was the presence of numerous pit-type hypoplastic defects, denoting a marked fluoride-induced disturbance also of the secretory stage of amelogenesis. Microradiography and scanning electron microscopy revealed an enhanced incremental pattern in the outer enamel of the fluorotic molars. Typically, the bottom of larger hypoplastic defects was underlain by a broad, grossly accentuated incremental line. Occurrence of larger hypoplasias was further associated with the presence of aprismatic enamel, the formation of which was attributed to a loss of the prism-forming (distal) portion of the Tomes’ processes of secretory ameloblasts. The findings in the miniature pigs closely parallel earlier observations on fluorotic enamel of free-ranging deer and wild boar from fluoride-polluted areas.
Similar content being viewed by others
References
Aoba T, Fejerskov O (2002) Dental fluorosis: chemistry and biology. Crit Rev Oral Biol Med 13:155–170
Boyde A (1967) The development of enamel structure. Proc R Soc Med 60:923–928
Boyde A (1997) Microstructure of enamel. In: Chadwick D, Cardew G (eds) Dental enamel. Ciba Foundation Symposium 205. Wiley, Chichester, pp 18–31
Briedermann L (1990) Schwarzwild, 2nd edn. DLV, Berlin
Davies AS (1990) Postnatal development of the lower canine and cheek teeth of the pig. Anat Histol Embryol 19:269–275
Dean HT (1934) Classification of mottled enamel diagnosis. J Am Dent Assoc 21:1421–1426
DenBesten PK (1994) Dental fluorosis: its use as a biomarker. Adv Dent Res 8:105–110
DenBesten PK, Crenshaw MA, Wilson MH (1985) Changes in the fluoride-induced modulation of maturation stage ameloblasts of rats. J Dent Res 64:1365–1370
Fejerskov O, Silverstone LM, Melsen B, Møller IJ (1975) Histological features of fluorosed human dental enamel. Caries Res 9:190–210
Fejerskov O, Thylstrup A, Larsen MJ (1977) Clinical and structural features and possible pathogenic mechanisms of dental fluorosis. Scand J Dent Res 85:510–534
Fejerskov O, Yaeger JA, Thylstrup A (1979) Microradiography of acute and chronic administration of fluoride on human and rat dentine and enamel. Arch Oral Biol 24:123–130
Fejerskov O, Josephsen K, Larsen MJ, Thylstrup A (1980) Cytological features of rat ameloblasts following long-term fluoride exposure. Caries Res 14:181–182
Fejerskov O, Richards A, Josephsen K (1983) Pathogenesis and biochemical findings of dental fluorosis in various species. In: Shupe JL, Peterson HB, Leone NC (eds) Fluorides – effects on vegetation, animals and humans. Paragon, Salt Lake City, pp 305–317
Fejerskov O, Manji F, Baelum V, Møller IJ (1988) Dental fluorosis – a handbook for health workers. Munksgaard, Copenhagen
Fejerskov O, Yanagiswa T, Tohda H, Larsen MJ, Josephsen K, Mosha HJ (1991) Posteruptive changes in human dental fluorosis – a histological and ultrastructural study. Proc Finn Dent Soc 87:607–619
Fejerskov O, Larsen MJ, Richards A, Baelum V (1994) Dental tissue effects of fluoride. Adv Dent Res 8:15–31
Fejerskov O, Richards A, DenBesten P (1996) The effect of fluoride on tooth mineralization. In: Fejerskov O, Ekstrand J, Burt BA (eds) Fluoride in dentistry. 2nd edn. Munksgaard, Copenhagen, pp 112–152
Josephsen K, Fejerskov O (1977) Ameloblast modulation in the maturation zone of the rat incisor enamel organ: A light and electron microscopic study. J Anat 124:45–70
Kierdorf H, Kierdorf U (1997) Disturbances of the secretory stage of amelogenesis in fluorosed deer teeth: a scanning electron-microscopic study. Cell Tissue Res 289:125–135
Kierdorf H, Kierdorf U, Boyde A (1997) A quantitative backscattered electron imaging study of hypomineralization and hypoplasia in fluorosed dental enamel of deer. Ann Anat 179:405–412
Kierdorf H, Kierdorf U, Richards A, Sedlacek F (2000) Disturbed enamel formation in wild boars (Sus scrofa L.) from fluoride polluted areas in Central Europe. Anat Rec 259:12–24
Kierdorf U, Kierdorf H (1989) A scanning electron microscopic study on surface lesions in fluorosed enamel of roe deer (Capreolus capreolus L.). Vet Pathol 26:209–215
Kierdorf U, Kierdorf H (1999) Dental fluorosis in wild deer: its use as a biomarker of increased fluoride exposure. Environ Monit Assess 57:265–275
Kierdorf U, Kierdorf H, Fejerskov O (1993) Fluoride-induced developmental changes in enamel and dentine of European roe deer (Capreolus capreolus L.) as a result of environmental pollution. Arch Oral Biol 38:1071–1081
Kierdorf U, Kierdorf H, Sedlacek F, Fejerskov O (1996) Structural changes in fluorosed dental enamel of red deer (Cervus elaphus L.) from a region with severe environmental pollution by fluorides. J Anat 188:183–195
Kirkham J, Robinson C, Weatherell JA, Richards A, Fejerskov O, Josephsen K (1988) Maturation in developing permanent porcine enamel. J Dent Res 67:1156–1160
Kodaka T, Mori R, Takiguchi R, Higashi S (1995) The structural patterns and mineralization values of prismless enamel, a case of mild enamel hypoplasia. Bull Tokyo Dent Coll 36:33–42
Lange Nordlund A, Lindskog S, Ekstrand J, Hammarström L (1986) Fluoride-induced cystic changes in the enamel organ of the rat molar. J Oral Pathol 15:87–92
Matsuo S, Inai T, Kurisu K, Kiyomiya K, Kurebe M (1996) Influence of fluoride on secretory pathway of the secretory ameloblast in rat incisor tooth germs exposed to sodium fluoride. Arch Toxicol 70:420–429
Monsour PA, Harbrow DJ, Warshawsky H (1989) Effects of acute doses of sodium fluoride on the morphology and the detectable calcium associated with secretory ameloblasts in rat incisors. J Histochem Cytochem 37:463–471
Newbrun E, Brudevold F (1960) Studies on the physical properties of fluorosed enamel – I microradiographic studies. Arch Oral Biol 2:15–20
Richards A, Kragstrup J, Nielsen-Kudsk F (1985) Pharmacokinetics of chronic fluoride ingestion in growing pigs. J Dent Res 64:425–430
Richards A, Kragstrup J, Josephsen K, Fejerskov O (1986) Dental fluorosis developed in post-secretory enamel. J Dent Res 65:1406–1409
Richards A, Likimani S, Baelum V, Fejerskov O (1992) Fluoride concentrations in unerupted fluorotic human enamel. Caries Res 26:328–332
Risnes S (1990) Structural characteristics of staircase-type Retzius lines in human dental enamel analyzed by scanning electron microscopy. Anat Rec 226:135–146
Risnes S (1998) Growth tracks in dental enamel. J Hum Evol 35:331–350
Robinson C, Kirkham J, Weatherell JA, Richards A, Josephsen K, Fejerskov O (1987) Developmental stages in permanent porcine enamel. Acta Anat 128:1–10
Roholm K (1937) Fluorine intoxication, a clinical-hygienic study. Lewis, London
Shearer TR, Kolstad DL, Suttie JW (1978) Bovine dental fluorosis: histologic and physical characteristics. Am J Vet Res 39:597–602
Shupe JL, Olson AE (1983) Clinical and pathological aspects of fluoride toxicosis in animals. In: Shupe JL, Peterson HB, Leone NC (eds) Fluorides – effects on vegetation, animals and humans. Paragon, Salt Lake City, pp 319–338
Simmelink JW, Lange A (1986) Ultrastructure of altered rat enamel beneath fluoride-induced cysts. J Oral Pathol 15:155–161
Smith CE, Nanci A, DenBesten PK (1993) Effects of chronic fluoride exposure on morphometric parameters defining the stages of amelogenesis and ameloblast modulation in rat incisors. Anat Rec 237:243–258
Suckling GW, Purdell-Lewis D (1982) Macroscopic appearance, microhardness and microradiographic characteristics of experimentally produced fluorotic lesions in sheep enamel. Caries Res 16:227–234
Suckling G, Thurley DC (1984) Histological, macroscopic and microhardness observations of fluoride-induced changes in the enamel organ and enamel of sheep incisor teeth. Arch Oral Biol 29:165–177
Suckling G, Thurley DC, Nelson DGA (1988) The macroscopic and scanning electron-microscopic appearance and microhardness of the enamel, and the related histological changes in the enamel organ of erupting sheep incisors resulting from a prolonged low daily dose of fluoride. Arch Oral Biol 33:361–373
Suttie JW, Carlson JR, Faltin EC (1972) Effects of alternating periods of high- and low-fluoride ingestion on dairy cattle. J Dairy Sci 55:790–804
Tataruch F, Kierdorf H (2003) Mammals as biomonitors. In: Markert BA, Breure AM, Zechmeister HG (eds) Bioindicators and biomonitors. Elsevier, Amsterdam, pp 737–772
Thylstrup A, Fejerskov O (1978) Clinical appearance of dental fluorosis in permanent teeth in relation to histologic changes. Comm Dent Oral Epidemiol 6:315–328
Thylstrup A, Fejerskov O (1979) A scanning electron microscopic and microradiographic study of pits in fluorosed human enamel. Scand J Dent Res 87:105–114
Tonge CH, McCance RA (1973) Normal development of the jaws and teeth in pigs, and the delay and malocclusion produced by calorie deficiencies. J Anat 115:1–22
Walton RE, Eisenmann DR (1974) Ultrastructural examination of various stages of amelogenesis in the rat following parenteral fluoride administration. Arch Oral Biol 19:171–182
Warshawsky H (1988) The teeth. In: Weiss L (ed) Cell and tissue biology. Urban, Baltimore, pp 597–640
Warshawsky H, Josephsen K, Thylstrup A, Fejerskov O (1981) The development of enamel structure in rat incisors as compared to the teeth of monkey and man. Anat Rec 200:371-399
Weaver ME, Sorenson FM, Jump EB (1962) The miniature pig as an experimental animal in dental research. Arch Oral Biol 7:17–24
Whitford GM (1997) Determinants and mechanisms of enamel fluorosis. In: Chadwick D, Cardew G (eds) Dental enamel. Ciba Foundation Symposium 205. Wiley, Chichester, pp 226–245
Wöltgens JHM, Lyaruu DM, Bronckers ALJJ, Bervoets TJM, Van Duin M (1995) Biomineralization during early stages of the developing tooth in vitro with special reference to secretory stage of amelogenesis. Int J Dev Biol 39:203–212
Acknowledgements
This investigation was supported by grants from the Aarhus University Research Foundation (grants Nos. E-2001-SUN-1-133 and E-2002-SUN-1-135). The pig mandibles were kindly donated by Merck Sharp & Dohme Research Laboratories, West Point, PA, USA. The authors would like to acknowledge the careful work of Anette Benner and Anne Larsen, who respectively measured the fluoride in bone and prepared the microradiographs.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kierdorf, H., Kierdorf, U., Richards, A. et al. Fluoride-induced alterations of enamel structure: an experimental study in the miniature pig. Anat Embryol 207, 463–474 (2004). https://doi.org/10.1007/s00429-003-0368-8
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00429-003-0368-8