title: Influence of hyaluronan on endometrial receptivity and embryo attachment in sheep.
abstract: An increasing number of reports suggests a role of hyaluronan (HA) in female reproduction and interest in its application in assisted reproduction is rising. However, there are contrasting data about the effectiveness of adding HA to the embryo-transfer medium on improving pregnancy rates. Using sheep as an experimental model, the studies reported here analysed the impact of HA infusion into the uterus on embryo attachment to uterine luminal epithelium (LE) and expression of selected markers of uterine receptivity. On Day 14 after natural mating (pre-attachment), uterine horns were infused with either (n=4 each): PBS (control), HA (1mg mL-1), HA+hyaluronidase 2 (Hyal2; 300IU mL-1) or 4-methyl-umbelliferone (HA-synthesis inhibitor; 4MU, 1mM). HA immunostaining on uterine sections collected on Day 17 was negative in the 4MU group and weak in the HA+Hyal2 group. In contrast to 4MU, which resulted in 100% attachment, HA infusion blocked embryo attachment in all treated animals. This was accompanied by the disappearance of mucin 1 and increased expression of osteopontin and CD44v6 in the LE of uteri with attached embryos. In conclusion, the presence of HA at the embryo-maternal interface during embryo implantation resulted in reduced endometrial receptivity and inhibited the interaction of trophoblasts with the LE, whereas clearance of HA favoured embryo attachment.
authors.affiliation: Reproduction Group, Department of Comparative Biomedical Sciences, The Royal Veterinary College, Hawkshead Lane, North Mymms, Hertfordshire AL97TA, UK.
authors.forename: Waleed F A
authors.initials: WFA
authors.lastname: Marei
authors.affiliation: Reproduction Group, Department of Comparative Biomedical Sciences, The Royal Veterinary College, Hawkshead Lane, North Mymms, Hertfordshire AL97TA, UK.
authors.forename: D Claire
authors.initials: DC
authors.lastname: Wathes
authors.affiliation: Reproduction Group, Department of Comparative Biomedical Sciences, The Royal Veterinary College, Hawkshead Lane, North Mymms, Hertfordshire AL97TA, UK.
authors.forename: Kabir A
authors.initials: KA
authors.lastname: Raheem
authors.affiliation: Department of Cytology and Histology, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt.
authors.forename: Omnia
authors.initials: O
authors.lastname: Mohey-Elsaeed
authors.affiliation: Reproduction Group, Department of Comparative Biomedical Sciences, The Royal Veterinary College, Hawkshead Lane, North Mymms, Hertfordshire AL97TA, UK.
authors.forename: Fataneh
authors.initials: F
authors.lastname: Ghafari
authors.affiliation: Reproduction Group, Department of Comparative Biomedical Sciences, The Royal Veterinary College, Hawkshead Lane, North Mymms, Hertfordshire AL97TA, UK.
authors.forename: Ali A
authors.initials: AA
authors.lastname: Fouladi-Nashta
mesh_terms: D000818:Animals; D010064:Embryo Implantation / Q000187:drug effects*; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000494:pharmacology*; D018396:Mucin-1 / Q000378:metabolism; D053495:Osteopontin / Q000378:metabolism; D011247:Pregnancy; D012756:Sheep; D014599:Uterus / Q000187:drug effects / Q000378:metabolism
chemical_list: D018960:Hyaluronan Receptors; D018396:Mucin-1; D053495:Osteopontin; D006820:Hyaluronic Acid