Placental function and structure at term is altered in broodmares fed with cereals from mid-gestation
Introduction
Since the early nineties, epidemiological studies in the Human species and experimental studies in model animals demonstrated that alterations of the maternal environment from periconception affects offspring development and health at adulthood [1]. This concept, called Developmental Origins of Health and Diseases (DOHaD), has also been demonstrated in the equine species [2].
In the horse, placentation is diffuse and epitheliochorial. The haemotrophic exchanges between maternal and fetal blood occur through the placental microcotyledons, that are intensely branched vascular structures covered with a haemotrophic trophoblast. The microcotyledons form interdigitations with the maternal endometrium to maximize nutrient exchanges. Additionally, histotrophic exchanges are mediated by pseudo-stratified trophoblastic cells specialized in the transfer of nutrients secreted by the uterine glands and take place across areolae located in-between the microcotyledons [[3], [4], [5]].
In the equine industry, breeders often feed broodmares with cereals in late pregnancy. In two previous studies, we demonstrated that feeding broodmares with cereals from mid-gestation increases maternal insulin resistance and the development of osteochondrosis in the foals, with potential detrimental effects on the horse industry economy [6,7]. Nevertheless, no studies have yet been conducted to understand the effect on the structure and function of the placenta. The present study follows up these previous works and investigates the effects of feeding broodmares with a moderate amount of cereals from mid-gestation on the structure and function of the placenta at term. Placentas were measured at delivery and their structure was analysed using the stereology method and the ImageJ software. Placental function was assessed through the analysis of gene expression after RNA sequencing.
Section snippets
Animals
The animal studies received ethical approval from the local ethics committee (« Comité Régional d’Ethique pour l’Expérimentation Animale du Limousin ») under protocol number 5-2013-5.
Twenty-two multiparous Saddlebred mares (median age 9y; range 6-19y) were fed cracked barley and forage (B, n = 10) or forage only (F, n = 12) from the 7th month of gestation until foaling. Management of mares from insemination to parturition has been previously described by Peugnet et al. [6]. In the present work,
Feto-placental biometry
Feto-placental biometry results are shown in Table 1.
At parturition, no difference was observed between groups for birthweight nor for placental weight, surface, volume and efficiency. Females tended to be heavier than males (+14.3%, p = 0.05) and had a heavier placenta (+5.5%, p = 0.049).
Placental morphometry
Stereological results are shown in Table 1.
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Microcotyledonary region: No difference in volume and surface was observed between both groups for haemotrophic trophoblast and connective tissue. The volume of
Effect of cereal ingestion on placental structure and function
In the present study, feeding pregnant mares with cereals from mid-gestation affected the structure and function of the placenta at term.
We observed previously that broodmares fed with cereals were more insulin resistant in late gestation and maintained an hyperglycaemic state throughout the day compared to mares fed with forages only [6]. In fact, In their paper on the same group of mares, Peugnet et al. concluded from the IVGTT data that F mares must have been insulin resistant [21]. Careful
Conclusion
In conclusion, feeding the pregnant mares with cereals from mid gestation alters the feto-maternal exchanges in the placenta by affecting the placental structure and function of the vessels and increasing the placental inflammation. Modifications of placental structure and function observed in placentas of insulin resistant dams are similar to those observed in diabetic and/or obese women and laminitic broodmares.
Conflicts of interest
There are no conflicts of interest for all authors.
Acknowledgments
This work was funded by grants from the "Institut Français du Cheval et de l’Equitation" and by the "Fonds Eperon" (FOETALIM project). The funders had no role in study design, data collection and analysis, decision to publish, nor preparation of the manuscript. The authors are grateful to the staff of the Institut Français du Cheval et de l’Equitation (IFCE) experimental farm (Domaine de la Valade, Chamberet, France) for care and management of animals.
References (48)
- et al.
Management of the pregnant mare and long-term consequences on the offspring
Theriogenology
(2016) - et al.
Scanning electron microscopy of the microcotyledonary placenta of the horse (Equus caballus) in the latter half of gestation
Placenta
(2000) - et al.
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction
Anal. Biochem.
(1987) - et al.
Effect of increased adiposity on insulin sensitivity and adipokine concentrations in different equine breeds adapted to cereal-rich or fat-rich meals
Vet. J.
(2016) - et al.
Longitudinal study of growth and osteoarticular status in foals born to between-breed embryo transfers
J. Equine Vet. Sci.
(2016) - et al.
Histomorphometry of the placental vasculature and microcotyledons in Thoroughbred mares with chronic laminitis
Theriogenology
(2017) Metabolic predispositions to laminitis in horses and ponies: obesity, insulin resistance and metabolic syndromes
J. Equine Vet. Sci.
(2008)- et al.
Vascular endothelial growth factor (VEGF) and VEGF-receptor expression in placenta of hyperglycemic pregnant women
Placenta
(2010) - et al.
Placental structure and inflammation in pregnancies associated with obesity
Placenta
(2011) - et al.
Obesity in pregnancy stimulates macrophage accumulation and inflammation in the placenta
Placenta
(2008)
Maternal obesity is associated with a lipotoxic placental environment
Placenta
Endothelial dysfunction — a major mediator of diabetic vascular disease
Biochim. Biophys. Acta - Mol. Basis Dis
Epigenetic modulation of DNA methylation by nutrition and its mechanisms in animals
Anim. Nutr.
Placental vasculogenesis is regulated by keratin-mediated hyperoxia in murine decidual tissues
Am. J. Pathol.
Morphology of equine allantochorion at the tip of the pregnant horn
J. Comp. Pathol.
Early developmental conditioning of later health and disease: physiology or pathophysiology?
Physiol. Rev.
Equine placentation
reprod. Fertil. Dev.
Anatomy of the placental barrier in the mare
J. Reprod. Fertil.
Effects of moderate amounts of barley in late pregnancy on growth, glucose metabolism and osteoarticular status of pre- weaning horses
PLoS One
Maternal nutrition during pregnancy affects testicular and bone development, glucose metabolism and response to overnutrition in weaned horses up to two years
PLoS One
Influence of maternal size on placental, fetal and postnatal growth in the horse. I. Development in utero
Reproduction
One-stop stereology: the estimation of 3D parameters using isotropic rulers
J. Microsc.
Core Team R, Nlme: Linear and Nonlinear Mixed Effects Models
An {R} Companion to Applied Regression
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