VN June 2023

Vetnews | Junie 2023 11 To enable this remarkable growth and development, uterine physiology needs to evolve in parallel with conceptus development. One of the defining events in the conceptus-directed adaptation of maternal physiology is the so-called ‘maternal recognition of pregnancy’ (MRP), a process by which the day 10 – 14 equine conceptus suppresses cyclical luteolysis, and thereby extends the lifespan of the primary corpus luteum (CL). This safeguards the supply of maternal progesterone required to stimulate endometrial production of the histotroph on which the conceptus depends for nutrition before the development of a stable placental attachment from around day 40. Conceptus-derived signals also combinewith luteal progesterone tomodify endometrial physiology inpreparation for implantation. Clearly, therefore, the way in which the early embryo and its dam communicate to ensure that uterine physiology is coordinated with embryonic development is critical to the successful maintenance of the pregnancy. Embryo development in the oviduct and descend into the uterus. The equine embryo remains in the oviduct for an unusually long interval and finally descends into the uterus on day six after ovulation. During its stay in the oviduct, the embryo’s genome is activated and progresses to the late morula or early blastocyst stage of development. Although little is known about embryo and oviduct interaction, the microenvironment and the oviduct ampulla play an active role in supporting early development; indeed, although in vitro produced (IVP) equine embryos reach the blastocyst stage at a similar time to in vitro embryos (7 – 8 days postfertilization), at this stage they contain many fewer cells, a higher percentage of which are apoptotic and, following transfer to a recipient mare, IVP embryos lag 2 – 3 days behind in development. They are more prone to early embryonic death. A positive influence of the oviduct on equine embryo development is also illustrated by the more rapid development and increased likelihood of reaching the blastocyst stage of 2 – 4 cell embryos transferred into the oviduct of a recipient mare soon after ICSI, compared to embryos maintained in vitro . Although it also appears that the developing embryo induces changes in oviductal epithelial cell gene and protein expression, the presence of an embryo in the oviduct does not appear to affect the mare’s subsequent ability to support pregnancy, as demonstrated by the high initial and ongoing pregnancy rates in well-synchronized embryo transfer recipient mares. Conversely, the early equine embryo has been reported to influence maternal physiology beyond the confines of the oviduct in the form of the‘early pregnancy factor’(EPF) reported to be detectable in the serum of pregnant mares from day two, postovulation. Although it is unclear whether EPF plays any further role in pregnancy recognition or maintenance, a reliable assay for EPF would be invaluable for investigating the scale and timing of embryonic loss and, potentially, for improving the efficiency of ET programs (e.g. by ensuring that only mares ‘guaranteed’ to deliver an embryo are flushed). Unfortunately, field trials of an ‘early conception factor’ assay were disappointing, with a high rate of false positives limiting the ability of the test to discriminate between pregnant and nonpregnant mares. The equine embryo’s oviductal phase is brought to an end by an enigmatic form of embryonic signalling, referred to as selective oviductal transport. Only developing embryos are able to reliably descend into the uterus, whereas unfertilized oocytes remain trapped in the oviductal ampulla. This selective transport is mediated primarily by prostaglandin E2 (PGE 2 ), which viable embryos begin to secrete from around day four postfertilization. The early postfertilization embryo is retained in the ampulla of the oviduct by a tightly closed ampullary-isthmic junction; ampullary-isthmic junction; the PGE 2 secreted by the developing morula relaxes the circular smooth muscle of the isthmus, causing it to dilate and allow the embryo to pass through into the uterus. Failure of viable embryos to initiate oviductal transport does not seem to occur since tubal pregnancy has not been reported as a complication in mares. Glycoprotein capsule Another unusual feature of equine pregnancy that both depends on and, almost certainly plays a role in, early embryo-maternal communication is the formation and subsequent disappearance of the acellular glycoprotein ‘capsule’ The capsule forms between the trophectoderm and zona pellucida very soon after the embryo enters the uterus. The mucin-like glycoproteins that initially make up the capsule are secreted by the trophectoderm; however, they are unable to cross-link to form a confluent structure in vitro . It, therefore, appears that capsule coalescence requires input from the endometrium, a supposition strengthened by the report of increased capsular glycoprotein production by IVP embryos exposed to Uterocalin. This progesterone-dependent endometrial protein associates strongly with the capsule of early uterine-stage embryos. Nevertheless, it is not entirely clear whether the primary uterine contribution to capsule formation is the delivery of structural elements, or by providing a microenvironment that facilitates the assembly of the trophectoderm-derived glycoproteins into a confluent structure. Soon after capsule formation is completed, the day seven embryo ‘hatches’ from its zona pellucida; however, its newly formed ‘tertiary embryo coat’remains as a physical barrier between the trophectoderm and the endometrium. The capsule subsequently increases in thickness until around day 17, developing a bilaminar appearance that may reflect an additional (presumably endometrial) source of structural components. Soon after embryo fixation (cessation of migration), however, dissolution of the capsule begins, with a loss of continuity somewhere between days 20 and 23; by day 30, the capsule has disintegrated completely. Although it is not known how the capsule is dissolved, there appears to be a central role for progesterone in stimulating enzymatic dissolution since induction of luteolysis shortly before conceptus fixation (day 16) prevents capsule dissolution and the desialylation and degradation of capsule-associated proteins associated with normal degradation. Article >>> 12