Intrauterine growth restriction after between-breed embryo transfer is associated with strong alterations in placental structure and function in horses
Résumé
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.