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.

Keywords: Conceptus; Cortisol; Endometrium; Interferon; Prostaglandin; Ruminant.

Figure 1

Schematic illustrating the effects of ovarian hormones and factors from the endometrium and conceptus trophectoderm on expression of elongation- and implantation-related genes in the endometrial epithelia of the ovine uterus during early pregnancy. Progesterone action for 8–10 days down-regulate expression of the progesterone receptor (PGR). The loss of PGR is correlated with the induction of many genes in the endometrial LE and sGE, including PTGS2 and HSD11B1 involved in prostaglandin (PG) and cortisol production, respectively, in both cyclic and pregnant ewes. If the ewe is pregnant, the trophectoderm synthesizes and secretes PGs, interferon tau (IFNT), and cortisol that act on the endometrium in a cell-specific manner to up-regulate the expression of many P4-induced genes that govern endometrial functions and/or elongation of the conceptus. Legend: GE, glandular epithelia; IFNT, interferon tau; LE, luminal epithelium; PG, prostaglandins; PGR, progesterone receptor; sGE, superficial glandular epithelia.

Figure 2

Schematic illustrating working hypothesis of the biological role of interferon tau (IFNT) and prostaglandins (PGs) in uterine function and conceptus elongation during early pregnancy in sheep. See text for detailed description. Legend: ABCC4, ATP-binding cassette, sub-family C (CFTR/MRP), member 4; CREB, cAMP responsive element binding protein; IFNAR, interferon (alpha, beta and omega) receptor; DP, prostaglandin D receptor (PTGDR); EP, prostaglandin E receptor (PTGER); FP, prostaglandin F receptor (PTGFR); IP, prostaglandin I receptor (PTGIR); PLA2, phospholipase A2; PPARD, peroxisome proliferator-activated receptor delta; PPARG, peroxisome proliferator-activated receptor gamma; PTGS2, prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase); PG Synthases, prostaglandin synthases (AKR1C3, PTGDS, PTGES, PTGFS, PTGIS, TBXAS); SLCO2A1, solute carrier organic anion transporter family, member 2A1 (prostaglandin transporter); TBXA2R, thromboxane A2 receptor.