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BACKGROUND Following embryo transfer (ET), the size and breed of the recipient mare can affect fetal development and subsequent post natal growth rate and insulin sensitivity in foals. OBJECTIVES To investigate placental adaptation in pregnancies where increased or restricted fetal growth was induced through ET between Pony, Saddlebred and Draught horses. STUDY DESIGN In vivo experiment. METHODS Control Pony (P, n = 21) and Saddlebred (S, n = 28) pregnancies were obtained by artificial insemination. Increased pregnancies were obtained by transferring Pony (P-D, n = 6) and Saddlebred (S-D, n = 8) embryos into Draught mares. Restricted pregnancies were obtained by transferring Saddlebred embryos into Pony mares (S-P, n = 6). Placental weight and surface were recorded and samples collected for stereology and analysis of expression of genes involved in placental growth, vascularisation and nutrient transport. Data were analysed by linear model. RESULTS S-P foals were growth retarded when compared with controls despite increased gestational length. Placental weight was reduced but placental surface density and volume fraction were increased. Placental expression of genes involved in growth and development and nutrient transfer was strongly reduced. In contrast, placental size and weight were increased in enhanced growth P-D and S-D foals. The trophoblastic surface density and the allantoic vessels surface density were decreased in P-D and S-D, respectively, both with very few modifications in gene expression. MAIN LIMITATIONS Control embryos were produced by artificial insemination whereas experimental embryos were produced by ET. CONCLUSIONS Placental structure and gene expression are modified after ET into a smaller or larger breed than that of the embryo. These adaptations contribute to the observed phenotype of foal growth restriction or enhanced growth at birth.

Remerciements à l'Institut Français du Cheval et de l'Equitation (IFCE); Developmental programming in equine species: relevance for the horse industry

Le fichier annexe contient une correction : The term "nutritional offer" appears incorrectly throughout the paper. The correct term should be "nutritional intake."Fig 1 and its caption appear incorrectly in the published article. Please see the correct Fig 1 and its caption below.; In stud management, broodmares are commonly fed concentrates in late pregnancy. This practice, however, was shown to correlate with an increased incidence of osteochondrosis in foals, which may be related to insulin sensitivity. We hypothesized that supplementation of the mare with barley in the last trimester of pregnancy alters the pre-weaning foal growth, glucose metabolism and osteoarticular status. Here, pregnant multiparous saddlebred mares were fed forage only (group F, n=13) or both forage and cracked barley (group B, n=12) from the 7th month of pregnancy until term, as calculated to cover nutritional needs of broodmares. Diets were given in two daily meals. All mares and foals returned to pasture after parturition. Post-natal growth, glucose metabolism and osteoarticular status were investigated in pre-weaning foals. B mares maintained an optimal body condition score (>3.5), whereas that of F mares decreased and remained low (

Members of COST Action FA0702 GEMINI "Maternal interaction with gametes and embryo", "FA1201 EPICONCEPT "Epigenetics and periconception environment", and BM 1308 SALAAM " Sharing advances on large animal models"; International audience; The study of early developmental conditioning of health and disease in adulthood is particularly relevant in the horse, which is bred mainly to perform in demanding sport challenges. On the basis of this concept, the management of the broodmare could be considered an effective means to produce animals with the desired features. Knowledge on the Developmental Origins of Health and Disease in the equine species remains relatively scarce, with some experimental studies and one single epidemiologic study. Data highlight the determinant role of the maternal environment for postnatal body conformation, immune response, energy homeostasis, osteoarticular status and thyroidal, adrenocortical, and cardiovascular functions of the foal. Most research, however, focuses on the first months/years after birth. Long-term effects on the adult horse phenotype have not been investigated so far.

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National audience; The risk of developing non-transmittable diseases such as diabetes, obesity or the metabolic syndrome, but also other non-transmittable illnesses is partly linked to maternal environment during pregnancy such as maternal nutrition, stress, pollution…. This is the basis of the Developmental Origins of Health and Disease (DOHaD). These epidemiological observations have been verified in laboratory animals but they are also very relevant to farm animals, and in particular horse breeding. The article summarizes current knowledge about fetal programming in the horse and introduces the results of the first years of study in the FOETALIM program.; On sait chez l'homme que les risques de développer des maladies métaboliques (diabète, obésité, syndrome métabolique) mais aussi d'autres affections non transmissibles sont en partie liés à l'environnement maternel (nutrition, stress, pollution...) durant la grossesse. On parle ainsi d'origines développementales de la santé et des maladies. Ces constatations épidémiologiques sont vérifiées chez les animaux de laboratoire mais peuvent aussi avoir des conséquences importantes dans le cadre de l'élevage du cheval. Cet article fait une synthèse de la littérature disponible dans ce domaine et présente le projet FOETALIM ainsi que les résultats des premières années d'étude.

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ln equids, placentationis diffus'e and the nutrient supply to the fetus is deterrnined byuterine size, which is correlated with materna!size. The size of the mare affects fetai development as shawn by embryo transfer (ET) between Panics and Thoroughbreds. In tum, insulin sensitivity in the newbom tüal and subsequent postnatal growth rate are affected. We enhanced or restricted fetal growth through ETusing Pony (P), Saddlebred (S), and Draft (D) horses and investigated placenta! morpho!ogy, structure, and fonction at tenn. Control pregnancies of P-P (n = 21), S-S (n = 28), and D-D (n = 8) were obtained by Al. Enhanced and restricted pregnancies were obtained by transferring P (P-D, n = 6) and S embryos (S-D, n = 8) into D mares orS embryos into P mares (S-P, n = 6), respective]y. Placenta!weight and surface were recorded at delivery. Samples were collected for stereology and RT-qPCR analysis of expression of genes involved in placenta!growth, vascularization, and nutrient transport. Housekeeping genes were RPL32, SCAMP3, and B2M. Data were analysed by Kruskal-Wallis followed by Dunn's post hoc test. Placenta!weight and surface were increased in S-S and in D-D compared with P-P, whereas S-S and D-D were not different. No histological changes were observed among contrais, but most genes had their expression decreased in P-P compared with S-S andD-D. The P-D foals hada 57% increased birthweight with heavier and largerplacentas than P-P foals. The S-D foals were similar to both S-S and D-D in te1ms ofbirthweight and placenta!weight and surface. No major modifications in placenta!histology or transcript levels were observed in both enhanced groups. In contrast, S-P foals had a 37% decreased birthweight with lighter and smaller placentas compared with S-S and S-D foals. Therewas no gross histological difference betweenS-P and S-S but the microcotyledonary surfacedensity was higher in S-P compared with S-D. Moreover, the expression of IGF2, !GF2R, SLC2Al, and eNOS was decreased in S-P compared with S-S. There was no difference in gene expression between S-P and P-P. In conclusion, intrauterine growth restriction led to marked changes in placenta!morphology, histology, and gene expression. The increased microcotyledonary surface density suggests a lengthening ofvillî, which could increase feto-maternal contact surface as a compensatory mechanism for the restricted uterine capacity. Surprisingly, placenta! adaptation to the restricted intrauterine enviromnent in S-P induced gene profiles resembling that of control P, whereas no difference was observed in enhanced pregnancies.

Article présenté à la 40ème Journée de la Recherche Equine, Paris, le 18 mars 2014; absent

In equids, placentation is diffuse and nutrient supply to the fetus is determined by uterine size. This correlates with maternal size and affects intra-uterine development and subsequent post-natal growth, as well as insulin sensitivity in the newborn. Long-term effects remain to be described. In this study, fetal growth was enhanced or restricted through ET using pony (P), saddlebred (S) and draft (D) horses. Control P-P (n = 21) and S-S (n = 28) pregnancies were obtained by AI. Enhanced and restricted pregnancies were obtained by transferring P or S embryos into D mares (P-D, n = 6 and S-D, n = 8) or S embryos into P mares (S-P, n = 6), respectively. Control and experimental foals were raised by their dams and recipient mothers, respectively. Weight gain, growth hormones and glucose homeostasis were investigated in the foals from birth to weaning. Fetal growth was enhanced in P-D and these foals remained consistently heavier, with reduced T3 concentrations until weaning compared to P-P. P-D had lower fasting glucose from days 30 to 200 and higher insulin secretion than P-P after IVGTT on day 3. Euglycemic clamps in the immediate post-weaning period revealed no difference in insulin sensitivity between P-D and P-P. Fetal growth was restricted in S-P and these foals remained consistently lighter until weaning compared to S-D, with elevated T3 concentrations in the newborn compared to S-S. S-P exhibited higher fasting glycemia than S-S and S-D from days 30 to 200. They had higher maximum increment in plasma glucose than S-D after IVGTT on day 3 and clamps on day 200 demonstrated higher insulin sensitivity compared to S-D. Neither the restricted nor the enhanced fetal environment affected IGF-1 concentrations. Thus, enhanced and restricted fetal and post-natal environments had combined effects that persisted until weaning. They induced different adaptive responses in post-natal glucose metabolism: an early insulin-resistance was induced in enhanced P-D, while S-P developed increased insulin sensitivity.

Genetics are responsible for determining the growth and size of different breeds of horses. Cross-breed embryo transfers were performed using Pony (P), Saddlebred (S) and Draft (D) horses to study growth and insulin-sensitivity in offspring. Control pregnancies (S-in Sand P-in-P) were obtained by Al. "Lush" pregnancies were obtained by transferring S (S in-D) and P embryos (P-in-D) into D mares. Restricted pregnancies were obtained by transferring S embryos into P mares (S-in-P). At 3 days, 4.5 months and one year, foals underwent an intravenous glucose tolerance test (IVGTT). At 6 and 18 months, insulin sensitivity was determined using a euglycemic hyperinsulinemic clamp. Birthweight was increased in P-in-D and S-in-D vs P-in-P and S-in-S controls (+57.2%,p=0.0007 and +8.9%,p=0.0597, respectively), and restricted in S-in-P vs S-in-S (-31.2%, p=0.0008). P-in O foals remained heavier than P-in-P until 18 months (+38.5%,p=0.0317), whereas S-in-D foals became similar to S-in-S between 6 and 18 months. S-in-P foals caught up with S-in-S foals after 9 months. Insulin response to glucose was increased in S-in-D and P-in-D foals at 3 days (p=0.0393 and p=0.0539), indicating insulin resistance. Results are pending for 4,5 months. Clamps at 6 months demonstrated the development of insulin resistance in P in-P vs S-in-S foals (p=0.0378). P-in-D remained insulin resistant and did not differ from P in-P. S-in-P and S-in-D foals were not different from S-in-S but insulin resistance was increased in S-in-D vs S-in-P foals (p=0.0293). IVGTT at one year and clamps at 18 months of age confirmed the increased insulin resistance of P-in-P vs S-in-S foals (p=0.0487), without effects of embryo transfer. Genetic programming of fetal and post-natal growth can be modified through embryo transfer in a larger or a smaller breed in the equine species and that glucose homeostasis is also affected post-natally. More data on plasma insulin concentrations will be available at the meeting.

Introduction Pregnant mares and post-weaning foals are often fed concentrates rich in soluble carbohydrates, together with forage. Recent studies suggest that the use of concentrates is linked to alterations of metabolism and the development of osteochondrosis in foals. The aim of this study was to determine if broodmare diet during gestation affects metabolism, osteoarticular status and growth of yearlings overfed from 20 to 24 months of age and/or sexual maturity in prepubertal colts. Material and methods Twenty-four saddlebred mares were fed forage only (n = 12, group F) or cracked barley and forage (n = 12, group B) from mid-gestation until foaling. Colts were gelded at 12 months of age. Between 20 and 24 months of age, all yearlings were overfed (+140% of requirements) using an automatic concentrate feeder. Offspring were monitored for growth between 6 and 24 months of age, glucose homeostasis was evaluated via modified frequently sampled intra veinous glucose tolerance test (FSIGT) at 19 and 24 months of age and osteoarticular status was investigated using radiographic examinations at 24 months of age. The structure and function of testicles from prepubertal colts were analyzed using stereology and RT-qPCR. Results Post-weaning weight growth was not different between groups. Testicular maturation was delayed in F colts compared to B colts at 12 months of age. From 19 months of age, the cannon bone was wider in B vs F yearlings. F yearlings were more insulin resistant at 19 months compared to B yearlings but B yearlings were affected more severely by overnutrition with reduced insulin sensitivity. The osteoarticular status at 24 months of age was not different between groups. Conclusion In conclusion, nutritional management of the pregnant broodmare and the growing foal may affect sexual maturity of colts and the metabolism of foals until 24 months of age. These effects may be deleterious for reproductive and sportive performances in older horses.

In pig production, the selection of hyperprolific animais has lead to an increased rate of intrauterine growth retarded (IUGR) piglets in litters. This is an important economie issue as these piglets display higher mortality rates, lower growth capacity and lower quality carcasses. The ptrrpose of this work was to investigate placenta!morphology and function during early (45d), mid (71d) and late gestation (112d) in pairs of control and IUGR siblings. Altogetber, 18 pairs were used (N=5, 6 and 7 at 45, 71 and 112 days, respective!y), each pair, but one, being of the same sex. The IUGR piglets were 25%, 33% and 41% lighter than controls. Relative uterine and placenta!proportions of blood vessels, connective tissue and trophoblast were measured by stereology. Placenta! expression of genes involved in fetal growth (IGF2), angiogenesis and vascularization (eNOS, VEGFa, FLTI, KDR), nutrient transport (GLUT3, SNAT2, LPL) and oxidative stress (SODl, SOD2) was measured by RT qPCR. Data were analyzed using Mann-Whitney test (morphometry) and ANOVA (gene expression). Morphometric analysis did not reveal any significant difference according to gestational age nor group. IGF2 expression was significantly increased in IUGR placenta at 71d of gestation (x 1.48, p

En production porcine, la sélection de truies hyperprolifiques a conduit à une augmentation de l'incidence de porcelets hypotrophes dans les portées (1 à 2 en moyenne par portée de 12 à 16 porcelets). Ces animaux ont une mortinatalité importante, une capacité de croissance réduite et produisent des carcasses de moindre qualité avec un taux de gras augmenté. Ils représentent donc une perte économique importante pour la filière. Les mécanismes précis conduisant à ce retard de croissance intra-utérin (RCIU) sont peu connus. L'objectif de cette étude était d'étudier le développement et la fonction placentaire chez des paires de porcelets RCIU et normaux issus de la même portée en début (45 jours), milieu (71jours) et fin de gestation (112 jours). Dix-huit paires de fœtus ont été utilisées (N=5, 6 et 7 à 45, 71 et 112 jours de gestation, respectivement, la durée de la gestation étant de 114 jours chez la truie). Toutes les paires, sauf une, étaient constituées d'individus de même sexe. Les porcelets RCIU étaient plus légers de 25%, 33% et 41% par rapport aux témoins à 45, 71 and 112 jours de gestation, respectivement. Les proportions relatives des vaisseaux sanguins, du tissu conjonctif et du trophoblaste ont été mesurées dans l'utérus et le placenta par stéréologie. L'expression placentaire de gènes impliqués dans la croissance fœtale (IGF2), l'angiogénèse et la vascularisation (eNOS, VEGFa, FLT1, KDR), les transports de nutriments (GLUT3, SNAT2, LPL) et le stress oxydant (SOD1, SOD2) a été mesurée par RT-qPCR à chaque stade. Les données ont été analysées avec un test non-paramétrique de Mann- Whitney (morphométrie) et par ANOVA (expression des gènes). L'analyse morphométrique n'a pas mis en évidence de différence significative dans les proportions tissulaires en fonction des groupes ou de l'âge. En termes d'expression de gènes, seule l'expression d'IGF2 était significativement augmentée dans les placentas des fœtus RCIU à 71 jours de gestation (x 1.48, p

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National audience; Chez le Cheval, la taille maternelle affecte la croissance foetale, postnatale et la sensibilité à l’insuline du poulain nouveau-né. Mais les effets à plus long terme n’ont pas été décrits. Le but de ce travail est d’induire une croissance fœtale augmentée ou restreinte via des transferts d’embryons entre poneys (P), chevaux de selle (S) et chevaux de trait (T) et de suivre le devenir des poulains jusqu’à 1 an. Les lots témoins «P dans P» (PP) et «S dans S» (SS) ont été obtenus par IA. Les croissances fœtales «augmentées» ont été obtenues par transfert d’embryons P (PT) et S (ST) dans des receveuses T et les croissances fœtales «restreintes» par transfert d’embryons S dans des receveuses P (SP). Les poulains ont été nourris par leurs receveuses jusqu’au sevrage à 6 mois. Les poids et taux plasmatiques des hormones thyroïdiennes (T3 et T4) et d’Insulin-like Growth Factor-1 (IGF1) des poulains ont été mesurés jusqu’à 1 an. La clairance du glucose et la sécrétion d’insuline ont été évaluées à 3 jours et 1 an avec un test IV de tolérance au glucose et la sensibilité à l’insuline avec un clamp hyperinsulinémique euglycémique à 6 mois (environ 20 jours post-sevrage). Les PT ont un poids de naissance significativement augmenté de 57,4% associé à une gestation plus courte de 6 jours comparé aux PP. Cette accélération de la croissance pondérale est conservée jusqu’à 1 an. Les taux plasmatiques de T3 et T4 sont significativement diminués, sans que ceux d’IGF1 ne soient affectés. A 3 jours, les PT ont une sécrétion d’insuline en réponse à l’injection de glucose significativement plus forte que les PP. Cette différence disparaît en post-sevrage puisque les clamps montrent que les PP deviennent résistants à l’insuline après sevrage (diminution significative du taux de métabolisme du glucose comparé aux SS), cette insulino-résistance se confirmant à 1 an (clairance du glucose significativement ralentie comparé aux SS). A contrario, les SP ont un poids de naissance significativement restreint de 37,2% associé à une gestation significativement plus longue de 13 jours comparé aux SS. La croissance pondérale est ralentie jusqu’au sevrage. Les taux plasmatiques de T3 et T4 sont significativement augmentés, sans que ceux d’IGF1 ne soient affectés. Suite au sevrage les SP semblent rattraper les SS jusqu’à 1 an. A 3 jours, l’augmentation de la glycémie en réponse à l’injection de glucose est significativement plus forte chez les SP que chez les ST. Cette différence significative entre les lots SP et ST est conservée immédiatement en post-sevrage (augmentation significative du taux de métabolisme du glucose chez les SP comparé aux ST). Cette augmentation de la sensibilité à l’insuline reste à confirmer à 1 an. Les ST ont des poids de naissance similaires aux SS et une accélération de la croissance pondérale est enregistrée jusqu’au sevrage, sans qu’aucune variation des taux plasmatiques de T3, T4 ou IGF1 ne soit observée. Ces résultats valident l’hypothèse d’une programmation in utero de la croissance et du métabolisme du glucose du poulain jusqu’à 1 an. L’augmentation de la croissance foetale des P oriente précocement le métabolisme vers le stockage de l’énergie, cette race développant naturellement une insulinorésistance après le sevrage. La restriction de la croissance foetale chez les S oriente le métabolisme vers la mobilisation de l’énergie. Les ralentissement (SP) et accélération (ST) de la croissance pondérale jusqu’au sevrage semblent être dus à la lactation respectivement insuffisante des receveuses P et en excès des T. Des effets marqués apparaissent sur les taux plasmatiques d’hormones thyroïdiennes T3 et T4 (baisse en cas d’augmentation des croissances foetale et post-natale chez les P ; augmentation en cas de restriction chez les S). Ces facteurs sont essentiels au développement harmonieux du squelette et le fait que la manipulation du développement précoce induise des modifications du métabolisme glucidique à long terme suggère que le métabolisme osseux pourrait également être affecté.

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