Conceptus elongation in ruminants: roles of progesterone, prostaglandin, interferon tau and cortisol

Abstract

The majority of pregnancy loss in ruminants occurs during the first three weeks after conception, particularly during the period of conceptus elongation that occurs prior to pregnancy recognition and implantation. This review integrates established and new information on the biological role of ovarian progesterone (P4), prostaglandins (PGs), interferon tau (IFNT) and cortisol in endometrial function and conceptus elongation. Progesterone is secreted by the ovarian corpus luteum (CL) and is the unequivocal hormone of pregnancy. Prostaglandins (PGs) and cortisol are produced by both the epithelial cells of the endometrium and the trophectoderm of the elongating conceptus. In contrast, IFNT is produced solely by the conceptus trophectoderm and is the maternal recognition of pregnancy signal that inhibits production of luteolytic pulses of PGF2α by the endometrium to maintain the CL and thus production of P4. Available results in sheep support the idea that the individual, interactive, and coordinated actions of P4, PGs, IFNT and cortisol regulate conceptus elongation and implantation by controlling expression of genes in the endometrium and/or trophectoderm. An increased knowledge of conceptus-endometrial interactions during early pregnancy in ruminants is necessary to understand and elucidate the causes of infertility and recurrent early pregnancy loss and provide new strategies to improve fertility and thus reproductive efficiency.

Interferon-tau and fertility in ruminants

“…The absence of oxytocin receptor expression in the cells of the endometrium prevents the release of luteolytic pulses of PGF2α, thereby maintaining the CL and adequate progesterone (P4) production. In addition to this antiluteolytic action on the CL, IFNT acts in a paracrine manner to induce or enhance endometrial expression of both classical and non-classical interferonstimulated genes (ISGs) in different cell compartments of the endometrium to facilitate uterine receptivity to implantation as well as further stimulate conceptus elongation and IFNT production (reviewed by Bazer et al 2011, Brooks et al 2014. Carefully orchestrated spatiotemporal alterations in gene expression within the endometrium are required for attachment of trophectoderm and implantation in all studied mammals, including ruminants.…”

Progesterone and conceptus-derived factors important for conceptus survival and growth

“…The ULF is derived primarily from transport and (or) synthesis and secretion of substances by the endometrial LE and glandular epithelium (GE), but also by the conceptus , and it is a complex and rather undefined mixture of proteins, lipids, amino acids, sugars (glucose, fructose), ions, and exosomes/microvesicles (Bazer, 1975;Gray et al, 2001;Bazer et al, 2012;Burns et al, 2014;Forde et al, 2014b). P4 induces the expression of a number of genes in the endometrial epithelium that are then further stimulated by factors from the conceptus (e.g., IFNT and PGs) and the endometrium itself Brooks et al, 2014;Lonergan and Forde, 2014). In turn, the genes and functions regulated by these hormones and factors in the endometrial epithelia cause specific changes in the uterine histotroph that govern conceptus survival and elongation (Faulkner et al, 2013;Forde et al, 2014a.…”

Embryo maternal immune interactions in cattle

“…In contrast to mouse and human species, implantation in cattle is non-invasive. It is characterized by a superficial attachment and adhesion of the trophectoderm to caruncular and intercaruncular areas, commencing about day 19 (see Brooks et al, 2014), for review. During implantation, bovine trophectoderm cells form binucleate cells (BNCs) as well as trinucleate cells (TNCs), TNCs are products of fusion between binucleate cells and uterine epithelial cells (Wooding and Beckers, 1987) and are only located in the endometrium (Wooding, 1992).…”