Influence of hyaluronan on endometrial receptivity and embryo attachment in sheep
Waleed F. A. Marei A B , D. Claire Wathes A , Kabir A. Raheem A C , Omnia Mohey-Elsaeed D , Fataneh Ghafari A and Ali A. Fouladi-Nashta A EA Reproduction Group, Department of Comparative Biomedical Sciences, The Royal Veterinary College, Hawkshead Lane, North Mymms, Hertfordshire AL97TA, UK.
B Department of Theriogenology, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt.
C Department of Veterinary Surgery and Theriogenology, Michael Okpara University of Agriculture, Umudike 445678, Nigeria.
D Department of Cytology and Histology, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt.
E Corresponding author. Email: afouladi@rvc.ac.uk
Reproduction, Fertility and Development 29(9) 1763-1773 https://doi.org/10.1071/RD16232
Submitted: 3 June 2016 Accepted: 12 September 2016 Published: 11 October 2016
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 (1 mg mL–1), HA + hyaluronidase 2 (Hyal2; 300 IU mL–1) or 4-methyl-umbelliferone (HA-synthesis inhibitor; 4MU, 1 mM). 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.
Additional keywords: 4MU, CD44, hyaluronic acid, implantation, MUC1, osteopontin.
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