Early pregnancy in the mare: old concepts revisited

Abstract

"Maternal recognition of pregnancy" (MRP) is commonly used to describe the ongoing embryo-maternal communication during early pregnancy that culminates in prevention of luteolysis and ensures ongoing progestin support. The conceptus-derived pregnancy recognition signal has not yet been identified in the mare. Although equine conceptuses produce substantial amounts of estrogens, there is a lack of evidence that estrogens are the pregnancy recognition signal in mares. Conceptus mobility is integral to MRP and is driven by conceptus-derived prostaglandin production. Cessation of conceptus mobility, referred to as fixation, is caused by increases in conceptus size and uterine tone and reduction in sialic acid content of the embryonic capsule. Gene expression profiling of equine preimplantation conceptuses revealed expression of neuraminidase 2 (NEU2), an enzyme that cleaves sialic acid from polysaccharide chains. Furthermore, secretion of NEU2 by conceptuses in vitro was functionally active; it appears therefore, that the conceptus itself regulates sialic acid content through expression of NEU2. Based on gene expression profiling, equine conceptuses express increasing amounts of fibrinogen during early development. Western blot analysis confirmed secretion of fibrinogen into culture medium when conceptuses were cultured in vitro and with immunohistochemistry, the acellular glycoprotein capsule of the conceptus had particularly intense staining for fibrinogen. Therefore, we hypothesize that conceptus-derived fibrinogen interacts with endometrial integrins to promote cessation of conceptus mobility and fixation. Indeed, next generation sequencing analysis of conceptus and endometrial samples 16 d after ovulation revealed that the integrin signaling pathway is significantly enriched in both sample types. Real-time reverse transcription polymerase chain reaction (RT-PCR) confirmed ITGAVB1 as the most abundant integrin receptor in endometrium; fibrinogen has the highest affinity for ITGAVB1 among integrins receptors to which it binds. Finally, the equine conceptus expresses increasing quantities of relaxin during preimplantation development, with the endometrium expressing relaxin receptors. In the pig, mouse, and human, relaxin is produced by the corpus luteum and is known to promote angiogenesis during early pregnancy. In summary, substantial advances in understanding MRP in the horse are underway.

Keywords: Fibrinogen; Horse; Integrin; Maternal recognition of pregnancy; NEU2; Relaxin.