Developmental origins of health and disease; Horse; Growth; Skeleton; Osteochondrosis
Abstract :
[en] The role of antenatal events on growth and predisposition to osteochondrosis (OC) was
investigated in foals born to between-breed embryo transfers. Pony (P), saddlebred (S), and
draft (D) horses were used. Control P-P (n ¼ 21) and S-S (n ¼ 28) pregnancies were obtained
by artificial insemination. Enhanced and restricted pregnancies were obtained by transferring
P or S embryos into D mares (P-D, n ¼ 6 and S-D, n ¼ 8) and S embryos into P mares
(S-P, n ¼ 6), respectively. Control and experimental foals were raised by their dams and
recipient mothers, respectively, and weaned at age 6 months. Body measurements were
recorded from birth to age 18 months. Osteochondrosis status was evaluated shortly after
weaning and at age 18 months. Fetal growth was enhanced in P-D foals with overgrowth of
most body segments until age 18 months. Fetal growth was restricted in S-P foals compared
with S-D foals. Body weight, shoulder, and hip width of S-P foals grew slower before weaning
but subsequently caught up after weaning. Other segments did not catch up, resulting in
reduced body weight and withers’ height in S-P compared with S-D foals at age 18 months.
The relative risk of developing OC was increased in restricted S-P foals compared with S-S
and S-D foals shortly after weaning where all S-P foals were OC positive. Only two S-P foals
were still OC positive at age 18 months. These data confirm the impact of the intrauterine
environment on growth, skeletal health, and possibly athletic capacities of horses.
Disciplines :
Veterinary medicine & animal health
Author, co-author :
Peugnet, Pauline
Mendoza García, Luis ; Université de Liège > Dép. clinique des animaux de compagnie et des équidés (DCA) > Anesthésiologie gén. et pathologie chirurg. des grds animaux
Wimel, Laurence
Duchamp, Guy
Dubois, Cédric
Reigner, Fabrice
Caudron, Isabelle ; Université de Liège > Dép. clinique des animaux de compagnie et des équidés (DCA) > Dép. clinique des animaux de compagnie et des équidés (DCA)
Deliège, Brigitte
Toquet, Marie-Pierre
Richard, Eric
Chaffaux, Stéphane
Tarrade, Anne
Lejeune, Jean-Philippe ; Université de Liège > Dép. clinique des animaux de compagnie et des équidés (DCA) > Anesthésiologie gén. et pathologie chirurg. des grds animaux
Serteyn, Didier ; Université de Liège > Dép. clinique des animaux de compagnie et des équidés (DCA) > Anesthésiologie gén. et pathologie chirurg. des grds animaux
[1] Barker, D.J., The fetal and infant origins of adult disease. BMJ, 301, 1990, 1111.
[2] Barker, D.J., Gluckman, P.D., Godfrey, K.M., Harding, J.E., Owens, J.A., Robinson, J.S., Fetal nutrition and cardiovascular disease in adult life. Lancet 341 (1993), 938–941.
[3] Barker, D.J., Hales, C.N., Fall, C.H., Osmond, C., Phipps, K., Clark, P.M., Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth. Diabetologia 36 (1993), 62–67.
[4] Barker, D.J., Osmond, C., Infant mortality, childhood nutrition, and ischaemic heart disease in England and Wales. Lancet 1 (1986), 1077–1081.
[5] Barker, D.J., Winter, P.D., Osmond, C., Margetts, B., Simmonds, S.J., Weight in infancy and death from ischaemic heart disease. Lancet 2 (1989), 577–580.
[6] Allen, W.R., Wilsher, S., Tiplady, C., Butterfield, R.M., The influence of maternal size on pre- and postnatal growth in the horse: III postnatal growth. Reproduction 127 (2004), 67–77.
[7] Peugnet, P., Wimel, L., Duchamp, G., Sandersen, C., Camous, S., Guillaume, D., et al. Enhanced or reduced fetal growth induced by embryo transfer into smaller or larger breeds alters post-natal growth and metabolism in pre-weaning horses. PLoS One, 9, 2014, e102044.
[8] Forhead, A.J., Ousey, J.C., Allen, W.R., Fowden, A.L., Postnatal insulin secretion and sensitivity after manipulation of fetal growth by embryo transfer in the horse. J Endocrinol 181 (2004), 459–467.
[9] Ousey, J.C., Fowden, A.L., Wilsher, S., Allen, W.R., The effects of maternal health and body condition on the endocrine responses of neonatal foals. Equine Vet J 40 (2008), 673–679.
[10] George, L.A., Staniar, W.B., Treiber, K.H., Harris, P.A., Geor, R.J., Insulin sensitivity and glucose dynamics during pre-weaning foal development and in response to maternal diet composition. Domest Anim Endocrinol 37 (2009), 23–29.
[11] van der Heyden, L., Lejeune, J.P., Caudron, I., Detilleux, J., Sandersen, C., Chavatte, P., et al. Association of breeding conditions with prevalence of osteochondrosis in foals. Vet Rec, 172, 2013, 68.
[12] Carlsten, J., Sandgren, B., Dalin, G., Development of osteochondrosis in the tarsocrural joint and osteochondral fragments in the fetlock joints of Standardbred trotters. I. A radiological survey. Equine Vet J Suppl 25 (1993), 42–47.
[13] Carlson, C.S., Cullins, L.D., Meuten, D.J., Osteochondrosis of the articular-epiphyseal cartilage complex in young horses: evidence for a defect in cartilage canal blood supply. Vet Pathol 32 (1995), 641–647.
[14] Henson, F.M., Davenport, C., Butler, L., Moran, I., Shingleton, W.D., Jeffcott, L.B., et al. Effects of insulin and insulin-like growth factors I and II on the growth of equine fetal and neonatal chondrocytes. Equine Vet J 29 (1997), 441–447.
[15] Rejno, S., Stromberg, B., Osteochondrosis in the horse. II. Pathology. Acta Radiol Suppl 358 (1978), 153–178.
[16] Olstad, K., Ytrehus, B., Ekman, S., Carlson, C.S., Dolvik, N.I., Early lesions of osteochondrosis in the distal tibia of foals. J Orthop Res 25 (2007), 1094–1105.
[17] Glade, M.J., Belling, T.H. Jr., Growth plate cartilage metabolism, morphology and biochemical composition in over- and underfed horses. Growth 48 (1984), 473–482.
[18] Glade, M.J., Reimers, T.J., Effects of dietary energy supply on serum thyroxine, tri-iodothyronine and insulin concentrations in young horses. J Endocrinol 104 (1985), 93–98.
[19] Pagan JD, Geor RJ, Caddel SE, Pryor PB, Hoekstra KE. The relationship between glycemic response and the incidence of OCD in thoroughbred weanlings: a field study. Proceedings of the AAEP 2001. p. 322–5.
[20] Savage, C.J., McCarthy, R.N., Jeffcott, L.B., Effects of dietary energy and protein on induction of dyschondroplasia in foals. Equine Vet J Suppl 16 (1993), 74–79.
[21] Ralston, S.L., Hyperglycemia/hyperinsulinemia after feeding a meal of grain to young horses with osteochondritis dissecans (OCD) lesions. Pferdeheilkunde 12 (1996), 320–322.
[22] Martin-Rosset, W., Equine nutrition—INRA nutrient requirements, recommended allowances and feed tables. 2014, Wageningen Academic Publishers, Wageningen, Netherlands.
[23] Schumann, G., Klauke, R., Canalias, F., Bossert-Reuther, S., Franck, P.F., Gella, F.J., et al. IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C. Part 9: reference procedure for the measurement of catalytic concentration of alkaline phosphatase International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Scientific Division, Committee on Reference Systems of Enzymes (C-RSE) (1)). Clin Chem Lab Med 49 (2011), 1439–1446.
[24] Jaeschke, G., Routine determination of free hydroxyproline in horse serum methods and normal values. Zentralbl Veterinarmed A 22 (1975), 89–101.
[25] Valette, J.P., Robert, C., Toquet, M.P., Denoix, J.M., Fortier, G., Evolution of some biochemical markers of growth in relation to osteoarticular status in young horses: results of a longitudinal study in three breeds. Equine Comp Exerc Physiol 4 (2007), 23–29.
[26] Denoix, J.M., Jacquet, S., Lepeule, J., Crevier-Denoix, N., Valette, J.P., Robert, C., Radiographic findings of juvenile osteochondral conditions detected in 392 foals using a field radiographic protocol. Vet J 197 (2013), 44–51.
[28] van Weeren, P.R., Aetiology, diagnosis and treatment of OC(D). Clin Tech Equine Pract 5 (2006), 248–258.
[29] Noguchi, K., Gel, Y., Brunner, R., Konietschke, F., nparLD: an R software package for non-parametric analysis of longitudinal data in factorial experiments. J Stat Softw 50 (2012), 1–23.
[30] Allen, W.R., Wilsher, S., Turnbull, C., Stewart, F., Ousey, J., Rossdale, P.D., et al. Influence of maternal size on placental, fetal and postnatal growth in the horse. I. Development in utero. Reproduction 123 (2002), 445–453.
[31] Biensen, N.J., Wilson, M.E., Ford, S.P., The impacts of uterine environment and fetal genotype on conceptus size and placental vascularity during late gestation in pigs. J Anim Sci 77 (1999), 954–959.
[32] Ferrell, C.L., Maternal and fetal influences on uterine and conceptus development in the cow: I. Growth of tissues of the gravid uterus. J Anim Sci 69 (1991), 1945–1953.
[33] Hokken-Koelega, A.C., De Ridder, M.A., Lemmen, R.J., Den Hartog, H., De Muinck Keizer-Schrama, S.M., Drop, S.L., Children born small for gestational age: do they catch up?. Pediatr Res 38 (1995), 267–271.
[34] Karlberg, J., Albertsson-Wikland, K., Growth in full-term small-for-gestational-age infants: from birth to final height. Pediatr Res 38 (1995), 733–739.
[35] Karlberg, J.P., Albertsson-Wikland, K., Kwan, E.Y., Lam, B.C., Low, L.C., The timing of early postnatal catch-up growth in normal, full-term infants born short for gestational age. Horm Res 48:Suppl 1 (1997), 17–24.
[36] De Blasio, M.J., Gatford, K.L., Robinson, J.S., Owens, J.A., Placental restriction of fetal growth reduces size at birth and alters postnatal growth, feeding activity, and adiposity in the young lamb. Am J Physiol Regul Integr Comp Physiol 292 (2007), R875–R886.
[37] Stock, K.F., Distl, O., Genetic correlations between conformation traits and radiographic findings in the limbs of German Warmblood riding horses. Genet Sel Evol 38 (2006), 657–671.
[38] Javaid, M.K., Lekamwasam, S., Clark, J., Dennison, E.M., Syddall, H.E., Loveridge, N., et al. Infant growth influences proximal femoral geometry in adulthood. J Bone Miner Res 21 (2006), 508–512.
[39] Oliver, H., Jameson, K.A., Sayer, A.A., Cooper, C., Dennison, E.M., Hertfordshire Cohort Study G. Growth in early life predicts bone strength in late adulthood: the Hertfordshire Cohort Study. Bone 41 (2007), 400–405.
[40] Dennison, E.M., Harvey, N.C., Cooper, C., Programming of osteoporosis and impact on osteoporosis risk. Clin Obstet Gynecol 56 (2013), 549–555.
[41] Doreau, M., Boulot, S., Recent knowledge on mare milk production: a review. Livest Prod Sci 22 (1989), 213–235.
[42] Doreau, M., Boulot, S., Methods of measurement of milk yield and composition in nursing mares: a review. Lait 69 (1989), 159–171.
[43] Cymbaluk, N.F., Smart, M.E., Bristol, F.M., Pouteaux, V.A., Importance of milk replacer intake and composition in rearing orphan foals. Can Vet J 34 (1993), 479–486.
[44] Price, P.A., Williamson, M.K., Lothringer, J.W., Origin of the vitamin K-dependent bone protein found in plasma and its clearance by kidney and bone. J Biol Chem 256 (1981), 12760–12766.
[45] Camarda, A.J., Butler, W.T., Finkelman, R.D., Nanci, A., Immunocytochemical localization of gamma-carboxyglutamic acid-containing proteins (osteocalcin) in rat bone and dentin. Calcif Tissue Int 40 (1987), 349–355.
[46] Delmas, P.D., Wahner, H.W., Mann, K.G., Riggs, B.L., Assessment of bone turnover in postmenopausal osteoporosis by measurement of serum bone Gla-protein. J Lab Clin Med 102 (1983), 470–476.
[47] Pastoureau, P., Meunier, P.J., Delmas, P.D., Serum osteocalcin (bone Gla-protein), an index of bone growth in lambs. Comparison with age-related histomorphometric changes. Bone 12 (1991), 143–149.
[48] Billinghurst, R.C., Brama, P.A., van Weeren, P.R., Knowlton, M.S., McIlwraith, C.W., Evaluation of serum concentrations of biomarkers of skeletal metabolism and results of radiography as indicators of severity of osteochondrosis in foals. Am J Vet Res 65 (2004), 143–150.
[49] Donabedian, M., van Weeren, P.R., Perona, G., Fleurance, G., Robert, C., Leger, S., et al. Early changes in biomarkers of skeletal metabolism and their association to the occurrence of osteochondrosis (OC) in the horse. Equine Vet J 40 (2008), 253–259.
[50] Lepage, O.M., Marcoux, M., Tremblay, A., Serum osteocalcin or bone Gla-protein, a biochemical marker for bone metabolism in horses: differences in serum levels with age. Can J Vet Res 54 (1990), 223–226.
[51] Chenu, C., Valentin-Opran, A., Chavassieux, P., Saez, S., Meunier, P.J., Delmas, P.D., Insulin like growth factor I hormonal regulation by growth hormone and by 1,25(OH)2D3 and activity on human osteoblast-like cells in short-term cultures. Bone 11 (1990), 81–86.
[52] Gouveia, C.H., Schultz, J.J., Bianco, A.C., Brent, G.A., Thyroid hormone stimulation of osteocalcin gene expression in ROS 17/2.8 cells is mediated by transcriptional and post-transcriptional mechanisms. J Endocrinol 170 (2001), 667–675.
[53] Lee, N.K., Sowa, H., Hinoi, E., Ferron, M., Ahn, J.D., Confavreux, C., et al. Endocrine regulation of energy metabolism by the skeleton. Cell 130 (2007), 456–469.
[54] Rijnen, K.E., van der Kolk, J.H., Determination of reference range values indicative of glucose metabolism and insulin resistance by use of glucose clamp techniques in horses and ponies. Am J Vet Res 64 (2003), 1260–1264.
[55] Lepage, O.M., DesCoteaux, L., Marcoux, M., Tremblay, A., Circadian rhythms of osteocalcin in equine serum. Correlation with alkaline phosphatase, calcium, phosphate and total protein levels. Can J Vet Res 55 (1991), 5–10.
[56] Ohlsson, C., Nilsson, A., Isaksson, O., Bentham, J., Lindahl, A., Effects of tri-iodothyronine and insulin-like growth factor-I (IGF-I) on alkaline phosphatase activity, [3H]thymidine incorporation and IGF-I receptor mRNA in cultured rat epiphyseal chondrocytes. J Endocrinol 135 (1992), 115–123.
[57] Smeets, T., van Buul-Offers, S., Influence of growth hormone and thyroxine on cell kinetics in the proximal tibial growth plate of Snell dwarf mice. Cell Tissue Kinet 19 (1986), 161–170.
[58] Magnusson, P., Degerblad, M., Saaf, M., Larsson, L., Thoren, M., Different responses of bone alkaline phosphatase isoforms during recombinant insulin-like growth factor-I (IGF-I) and during growth hormone therapy in adults with growth hormone deficiency. J Bone Miner Res 12 (1997), 210–220.
[59] Yamamoto, T., Diagnostic value of free hydroxyproline in horse serum. Bull Of Equine Res Inst, 1981, 3–83.
[60] van den Boom, R., Brama, P.A., Kiers, G.H., de Groot, J., van Weeren, P.R., Assessment of the effects of age and joint disease on hydroxyproline and glycosaminoglycan concentrations in synovial fluid from the metacarpophalangeal joint of horses. Am J Vet Res 65 (2004), 296–302.
[61] Ducy, P., Desbois, C., Boyce, B., Pinero, G., Story, B., Dunstan, C., et al. Increased bone formation in osteocalcin-deficient mice. Nature 382 (1996), 448–452.
[62] Mayne, R., Cartilage collagens. What is their function, and are they involved in articular disease?. Arthritis Rheum 32 (1989), 241–246.
[63] Kuettner, K.E., Biochemistry of articular cartilage in health and disease. Clin Biochem 25 (1992), 155–163.
[64] Garnero, P., Aronstein, W.S., Cohen, S.B., Conaghan, P.G., Cline, G.A., Christiansen, C., et al. Relationships between biochemical markers of bone and cartilage degradation with radiological progression in patients with knee osteoarthritis receiving risedronate: the Knee Osteoarthritis Structural Arthritis randomized clinical trial. Osteoarthritis Cartilage 16 (2008), 660–666.
[65] Fyfe, E.V., Biomarker assessment for detection of joint pathology in horses and evaluation of the nutritional supplement Steadfast Equine as a therapeutic. 2012, University of Missouri-Columbia, Columbia, MO, USA.
[66] Ytrehus, B., Carlson, C.S., Ekman, S., Etiology and pathogenesis of osteochondrosis. Vet Pathol 44 (2007), 429–448.
[67] Jeffcott, L.B., Henson, F.M., Studies on growth cartilage in the horse and their application to aetiopathogenesis of dyschondroplasia (osteochondrosis). Vet J 156 (1998), 177–192.
[68] Lecocq, M., Girard, C.A., Fogarty, U., Beauchamp, G., Richard, H., Laverty, S., Cartilage matrix changes in the developing epiphysis: early events on the pathway to equine osteochondrosis?. Equine Vet J 40 (2008), 442–454.
[69] Cooper, C., Fall, C., Egger, P., Hobbs, R., Eastell, R., Barker, D., Growth in infancy and bone mass in later life. Ann Rheum Dis 56 (1997), 17–21.
[70] Dennison, E., Cole, Z., Cooper, C., Diagnosis and epidemiology of osteoporosis. Curr Opin Rheumatol 17 (2005), 456–461.
[71] Trumble TN, Brown MP, Merritt KA. Decreased aggrecan (G1/G2) to CTX II ratios in synovial fluid of horses with osteochondral injury. 55th Annual meeting of the orthopaedic research society. Las Vegas, USA 2009.
[72] Cleary, O.B., Trumble, T.N., Merritt, K.A., Brown, M.P., Effect of exercise and osteochondral injury on synovial fluid and serum concentrations of carboxy-terminal telopeptide fragments of type II collagen in racehorses. Am J Vet Res 71 (2010), 33–40.
[73] Ekman, S., Rodriguez-Martinez, H., Ultrastructural localization of alkaline phosphatase activity in the normal and osteochondrotic joint cartilage of growing pigs. Acta Anat (Basel) 140 (1991), 26–33.
[74] Voute, L.C., Henson, F.M., Platt, D., Jeffcott, L.B., Osteochondrosis lesions of the lateral trochlear ridge of the distal femur in four ponies. Vet Rec, 168, 2011, 265.
[75] van der Heyden, L., Serteyn, D., Caudron, I., Verwilhen, D., Lejeune, J.P., Prévalence de l'ostéochondrose chez le cheval de sport de Wallonie. Ann de médecine vétérinaire 152 (2008), 131–137.
[76] Thompson, J.G., Kind, K.L., Roberts, C.T., Robertson, S.A., Robinson, J.S., Epigenetic risks related to assisted reproductive technologies: short- and long-term consequences for the health of children conceived through assisted reproduction technology: more reason for caution?. Hum Reprod 17 (2002), 2783–2786.
[77] McEvoy, T.G., Robinson, J.J., Sinclair, K.D., Developmental consequences of embryo and cell manipulation in mice and farm animals. Reproduction 122 (2001), 507–518.
[78] Franciosi, F., Lodde, V., Goudet, G., Duchamp, G., Deleuze, S., Douet, C., et al. Changes in histone H4 acetylation during in vivo versus in vitro maturation of equine oocytes. Mol Hum Reprod 18 (2012), 243–252.
[79] Donjacour, A., Liu, X., Lin, W., Simbulan, R., Rinaudo, P.F., In vitro fertilization affects growth and glucose metabolism in a sex-specific manner in an outbred mouse model. Biol Reprod, 90, 2014, 80.
[80] Collas, C., Fleurance, G., Cabaret, J., Martin-Rosset, W., Wimel, L., Cortet, J., et al. How does the suppression of energy supplementation affect herbage intake, performance and parasitism in lactating saddle mares?. Anim 8 (2014), 1290–1297.