Obesity is a growing concern in horses. The effects of maternal obesity on maternal metabolism and low-grade inflammation during pregnancy, as well as offspring growth, metabolism, low-grade ...inflammation, testicular maturation and osteochondrotic lesions until 18 months of age were investigated.
Twenty-four mares were used and separated into two groups at insemination according to body condition score (BCS): Normal (N, n = 10, BCS ≤4) and Obese (O, n = 14, BCS ≥4.25). BCS and plasma glucose, insulin, triglyceride, urea, non-esterified fatty acid, serum amyloid A (SAA), leptin and adiponectin concentrations were monitored throughout gestation. At 300 days of gestation, a Frequently Sampled Intravenous Glucose Tolerance Test (FSIGT) was performed. After parturition, foals' weight and size were monitored until 18 months of age with plasma SAA, leptin, adiponectin, triiodothyronine (T3), thyroxine (T4) and cortisol concentrations measured at regular intervals. At 6, 12 and 18 months of age, FSIGT and osteoarticular examinations were performed. Males were gelded at one year and expression of genes involved in testicular maturation analysed by RT-qPCR.
Throughout the experiment, maternal BCS was higher in O versus N mares. During gestation, plasma urea and adiponectin were decreased and SAA and leptin increased in O versus N mares. O mares were also more insulin resistant than N mares with a higher glucose effectiveness. Postnatally, there was no difference in offspring growth between groups. Nevertheless, plasma SAA concentrations were increased in O versus N foals until 6 months, with O foals being consistently more insulin resistant with a higher glucose effectiveness. At 12 months of age, O foals were significantly more affected by osteochondrosis than N foals. All other parameters were not different between groups.
In conclusion, maternal obesity altered metabolism and increased low-grade inflammation in both dams and foals. The risk of developing osteochondrosis at 12 months of age was also higher in foals born to obese dams.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
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.
Primiparous mares are known to produce smaller foals than multiparous mares. This difference seems to be partly explained by the reduced exchange surface and volume of the placental villi in ...primiparous compared to multiparous placentas. The effect of maternal parity on foals' post-natal growth, metabolism and sexual maturation, however, has been given little consideration. The objectives of this work were to analyse placental biometry and structure at term, growth of foals and yearlings, their metabolism and testicular maturation at one year of age.
Twenty multiparous mares (M), aged over 6 years and 12 primiparous mares (P), aged up to 5 years were artificially inseminated with the same stallion and monitored the same way until foaling. At birth, foals and placentas were measured and placentas were sampled above at the umbilical cord insertion, as well as in the pregnant and the non-pregnant horn to perform stereological analyses. Foals were weighed and measured until 540 days of age. At 120 and 360 days of age, an Intravenous Glucose Tolerance Test was performed on foals and yearlings. At 360 days of age, the males were castrated and testicular maturation analysed by RT-qPCR.
At birth, P dams produced lighter and smaller foals and placentas. The foal birth weight to placental surface ratio was lower in the P compared to the M group. P Foals remained lighter than M foals until 360 days of age and smaller until at least 540 days of age. At 120 days of age, P foals had a higher glucose tolerance than M foals, and then may be less mature than M foals in terms of the control of their glucose homeostasis. At 360 days of age, the testicles of prepubertal P stallions were less mature in the P vs the M group.
In conclusion, primiparous dams produce intrauterine growth restricted, less mature and smaller foals compared to multiparous dams with altered metabolism and growth until at least 540 days of age. These differences could affect the sport career of these foals, especially if it begins at an early age.
•Placentas of primiparous mares are lighter with a reduced capacity of histotrophic nutrition at term.•Foals born to primiparous mares are lighter until 12 months of age and smaller until 18 months of age.•Foals born to primiparous mares have less mature metabolic and male reproductive functions.
Ponies and sometimes draft horses are often used as experimental models for horses although size and metabolic parameters are known to vary between horse breeds. So far, there is little information ...about differences of placental structure and no information about differences of placental function between breeds. The aim of this study was to investigate differences in placental size, structure and function at birth in relation to foal size and weight in ponies, Saddlebred and draft horses. Pony, Saddlebred and draft horse pregnancies were obtained by artificial insemination over 2 successive breeding seasons. Foals and total fetal membranes (TFM) were weighed and placentas measured for surface area at term. Placentas were sampled above the umbilical cord insertion. Surface density and volume fraction of the different cellular components of the placenta were measured on histological sections using stereology. The expression of genes involved in growth and development, nutrient transfer and vascularization was compared between groups. Foals and TFM were lighter at birth in ponies than Saddlebred horses, and both were lighter compared to draft horses. The surface density and volume fraction of microcotyledonary vessels was increased in pony compared to Saddlebred placentas. The relative expression of genes involved in growth and development was different between breeds and increased with maternal, fetal and placental weight. Primiparous dams produced lighter foals and smaller placentas, associated with a decreased volume fraction of microcotyledonary vessels and genes involved in growth and development and vascularization. Foal sex had little effect on placental structure and function as the expression of only one gene differed according to sex, with EGFR expression being decreased in placentas of females compared to males. In conclusion, foal and placental weight, as well as placental expression of genes involved in growth and development were correlated with maternal size. Placental structure also differed between breeds, with a stronger difference between ponies and both breeds of horses.
•Ponies seem to have a more efficient placenta than Saddlebred and draft horses.•Ponies seem to have a different placental function than Saddlebred and draft placentas.•Breed should be chosen carefully for pregnancy experiments.
Feeding pregnant broodmares with cereal concentrates has been shown to increase maternal insulin resistance and affect foal metabolism in the short and long-term. These effects are likely to be ...mediated by the placenta. Here, we investigated feto-placental biometry and placental structure and function at term in mares fed with or without cereals concentrates.
From 7 months of gestation, 22 multiparous mares were fed forage only (group F (n = 12)) or received forage and cracked barley (group B (n = 10)) until foaling. Foals and placentas were weighed and placental samples were collected above the umbilical cord insertion at birth. Placental histological structure was studied by stereology. A RNAseq analysis was performed on 9 placentas of each group. Enrichment of gene sets was analysed using the Gene Set Enrichment Analysis (GSEA) software using the KEGG and GO databases.
No difference in feto-placental biometry was observed between groups. The volume of microcotyledonary vessels was decreased in B placentas and the vascular wall of allantoic arterioles was thickened. Gene sets involved in neutral amino acids, folate and anions transport and fatty acids, cholesterol and folate degradation were down-regulated while gene sets involved in RNA expression, inflammation and vascularisation were up-regulated in B placentas.
Feeding pregnant mares with concentrates from mid-gestation alters the placental function and structure as observed in other species in cases of maternal insulin resistance.
•Feeding cereals to broodmares in late gestation alters the vasculature development of placentas.•Feeding cereals to broodmares in late gestation alters the placental transcriptome.•Insulin resistance in late gestation in the horse alters the placental structure and function as observed in obese women.
In human obstetrics, placental vascularisation impairment is frequent as well as linked to severe pathological events (preeclampsia and intrauterine growth restriction), and there is a need for ...reliable methods allowing non-invasive evaluation of placental blood flow. Uteroplacental vascularisation is complex, and animal models are essential for the technical development and safety assessment of these imaging tools for human clinical use; however, these techniques can also be applied in the veterinary context. This paper reviews how ultrasound-based imaging methods such as 2D and 3D Doppler can provide valuable insight for the exploration of placental blood flow both in humans and animals and how new approaches such as the use of ultrasound contrast agents or ultrafast Doppler may allow to discriminate between maternal (non-pulsatile) and foetal (pulsatile) blood flow in the placenta. Finally, functional magnetic resonance imaging could also be used to evaluate placental blood flow, as indicated by studies in animal models, but its safety in human pregnancy still requires to be confirmed.
Animal models are of critical importance in biomedical research. Although rodents and lagomorphs are the most commonly used species, larger species are required, especially when surgical approaches ...or new medical devices have to be evaluated. In particular, in the field of perinatal medicine, they are critical for the evaluation of new pharmacologic treatments and the development of new invasive procedures in fetuses. In some areas, such as developmental genetics, reproductive biotechnologies and metabolic programming, the contribution of ruminants is essential. The current report focuses on some of the most outstanding examples of great biomedical advances carried out with ruminant models in the field of perinatal research. Experiments recently carried in our research unit using ruminants are also briefly described.
Abstract Objectives We have previously validated the use of l -nitro-arginine methyl ester ( l -NAME), a nitric oxide synthase inhibitor, to induce placental hypoperfusion in a rabbit model. Here, ...the effects of l -NAME on placental vascularization were explored. Transplacental transfer of l -NAME and/or its active metabolite, NG-nitro- l -arginine (L-NOARG), was evaluated. Methods 25 pregnant female rabbits were allocated on day 24 to one of 5 groups: l -NAME groups (31.35, 62.5, 125 and 250 mg/kg/day) or Control group (C). On Day 28, the labyrinthine area was analyzed for stereology and gene expression. l -NAME and L-NOARG were quantified in maternal and fetal blood. Results The volume density of fetal vessels was significantly decreased in l -NAME (including 62.5–250 mg/kg/day which induced an IUGR) compared to C groups. l -NAME induced an increase of the volume and surface density of the maternal blood space. The trophoblast volume density remained unchanged as well as the surface density of fetal vessels. Relative expression of eNOS, VEGFA, VEGFR-1 and VEGFR-2 in placentas was not affected by 125 mg/kg/day l -NAME treatment, whereas IGF-2 expression was significantly increased in this l -NAME group compared to C. l -NAME was not detected in maternal nor fetal plasma. In contrast, fetal to maternal L-NOARG ratio was 100% in all l -NAME groups. Conclusion These data demonstrate that l -NAME induced placental hypovascularization. The active L-NOARG metabolite is found in maternal and fetal plasma at similar concentrations. This could impact the fetal growth and reduces the interest of this model to study fetal outcomes of placental hypoperfusion.
Abstract Objectives Our objective was to evaluate the 3D power Doppler angiography (PDA) in terms of feasibility and ability to detect placental hypo-perfusion in an experimental rabbit model of ...intrauterine growth restriction (IUGR). Study design 14 pregnant females were treated with NG-nitro-L-arginine methylester (L-NAME), a nitric oxide synthase inhibitor, from day 24 to day 28 of gestation, to induce an IUGR. Concomitantly, 8 pregnant rabbits were used as controls. On day 28, 3D power Doppler indices were quantified in each utero-placental unit. Morphological examination of the placentas for the control group ( n = 4) and the L-NAME group (500 mg/day, n = 4) were performed with immunohistochemical staining to discriminate the fetal capillaries in the labyrinthine area. Results A total of 180 live fetuses were obtained, 108 from the L-NAME group and 72 from the control group. G28 fetal weight was significantly lower in the L-NAME group than in the control group (27.40 ± 0.55 g vs 33.14 ± 0.62 g, p < 0.0001). In the L-NAME group the vascularization index (VI), flow index (FI) and vascularization flow index (VFI) were significantly lower than in the control group (2.6 1.4; 6.0 vs 7.6 3.5; 12.6, p < 0.05; 28.7 26.5; 31.3 vs 32.9 28.3; 38.1, p < 0.05; 0.8 0.4; 1.8 vs 2.5 1.1; 4.1, p < 0.05, for VI, FI and VFI, respectively). Morphological examinations revealed a substantial disorganization of the placental vascular architecture in the L-NAME group. Conclusion This experimental study demonstrates that quantitative 3D PDA indices are sensitive enough to detect placental vascular insufficiency in an experimental rabbit model of IUGR.
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