Introduction

To complete its development, an embryo must progress through a series of predetermined steps that sequentially promote its development from an undifferentiated single‐cell organism into a healthy neonatal animal. In mammalian species, establishment and maintenance of pregnancy requires a number of closely integrated signals between the ovary, uterus and conceptus. Disruption of the synchrony between the uterine environment and the growing and differentiating conceptus during early pregnancy can result in failure to maintain pregnancy.

Regardless of species, reproductive rates are dependent on the number of oocytes ovulated and fertilised as well as embryonic, foetal and neonatal survival. In detailed studies of mammalian species, only 50 to 70% of successfully fertilised oocytes typically give rise to live, healthy offspring. Much of the embryonic and foetal mortality observed in domestic mammals occurs early in pregnancy, before apposition and attachment to the uterus takes place. Prior to attachment, embryo growth includes cleavage‐stage development and blastocyst formation. At this stage, in ruminants and pigs, rapid elongation serves to ensure that the developing conceptus establishes maximum contact with the endometrium. In contrast, the equine embryo remains compact and spherical rather than undergoing elongation and migrates between the two uterine horns until implantation occurs. Such conceptus migration is deemed to be necessary for maternal recognition and maintenance of pregnancy in the mare. In addition, this migration probably facilitates more effective uptake of uterine secretions, which are essential sources of nutrients prior to implantation.

The term early embryonic mortality refers to failure of the embryo to survive in utero during the initial stages of pregnancy. Synonyms for early embryonic mortality include early embryonic death and embryonic loss but these terms should not be confused with foetal death, foetal mortality or abortion, all of which occur later in gestation. The term pregnancy loss is all‐encompassing and includes loss of the embryo or foetus irrespective of the time during gestation at which it occurs.

Although substantial prenatal mortality occurs in all mammals, there are significant species differences in the extent, timing and consequences of embryonic loss. In humans, pregnancy loss, termed a miscarriage or abortion depending on the time during gestation when it occurs, can cause great emotional distress. In farm animals, embryo mortality is associated with production inefficiencies which may have serious financial implications. Embryonic loss leads to a reduction in litter size in pigs and prolific breeds of sheep. In cattle and sheep with only one ovulation at each oestrus, it leads to an increased interval between births which, particularly in seasonal pasture‐based systems of production, can have significant cost implications. In monotocous domestic species, those producing a single offspring at birth, death of the embryo results in termination of the pregnancy. In suckler beef production systems, in particular, failure to produce an offspring impacts financially as the calf represents the primary source of income. In contrast, in polytocous species, those producing more than one offspring, such as the pig, death of individual embryos within the uterus does not necessarily affect continuation of pregnancy. Indeed, it is important to consider that at least some embryonic loss may represent biological selection aimed at elimination of low quality embryos.

Establishment of pregnancy in cattle

Following oocyte fertilisation in the uterine tube, the resulting embryo(s) is transported towards the uterus as it undergoes the first mitotic cleavage divisions. As an example, the bovine embryo enters the uterus at about the 16‐cell stage on approximately day 4 of pregnancy. Subsequently, it forms a compact ball of cells, referred to as a morula, in which cell‐to‐cell tight junctions are first established. By day 7, the embryo becomes a blastocyst consisting of an inner cell mass which, after further differentiation, gives rise to the embryo, and the trophectoderm, which forms the foetal membranes. After hatching from the zona pellucida on days 9 to 10, the blastocyst continues to grow and change its morphology from a spherical to ovoid shape during a transitional phase preceding the elongation or outgrowth of the trophectoderm to a filamentous form that begins between days 12 and 14. On day 13, the ovoid conceptus is about 2 mm in length and it continues to elongate, reaching a length of about 60 mm by day 16. After day 19, the fully elongated conceptus begins implantation with firm apposition and attachment of the trophectoderm to endometrial luminal epithelium.