Establishment and maintenance of pregnancy results from signaling by the conceptus (embryo/fetus and associated extraembryonic membranes) and requires progesterone produced by the corpus luteum (CL). In most mammals, hormones produced by the trophoblast maintain progesterone production by acting directly or indirectly to maintain the CL. In domestic animals (ruminants and pigs), hormones from the trophoblast are antiluteolytic in that they act on the endometrium to prevent uterine release of luteolytic prostaglandin F2 alpha (PGF). In cyclic and pregnant sheep, progesterone negatively autoregulates expression of the progesterone receptor (PR) gene in the endometrial luminal (LE) and superficial glandular epithelium (GE). Available evidence in cyclic sheep indicates that loss of the PR is closely followed by increases in epithelial estrogen receptors (ER) and then oxytocin receptors (OTR), allowing oxytocin to induce uterine release of luteolytic PGF pulses. In pregnant sheep, the conceptus trophoblast produces interferon tau (IFN tau) that acts on the endometrium to inhibit transcription of the ER alpha gene directly and the OTR gene indirectly to abrogate development of the endometrial luteolytic mechanism. Subsequently, sequential, overlapping actions of progesterone, IFN tau, placental lactogen (PL) and growth hormone (GH) comprise a hormonal servomechanism that regulates endometrial gland morphogenesis and terminal differentiated function to maintain pregnancy in sheep. In pigs, the conceptus trophoblast produces estrogen that alters the direction of PGF secretion from an endocrine to exocrine direction, thereby sequestering luteolytic PGF within the uterine lumen. Conceptus estrogen also increases expression of fibroblast growth factor 7 (FGF-7) in the endometrial LE that, in turn, stimulates proliferation and differentiated functions of the trophectoderm, which expresses the FGF-7 receptor. Strategic manipulation of these physiological mechanisms can offer therapeutic schemes to improve uterine capacity, conceptus survival and reproductive health.

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Conceptus signals for establishment and maintenance of pregnancy.

Interferons and progesterone for establishment and maintenance of pregnancy: interactions among novel cell signaling pathways.

Pig blastocyst-uterine interactions.

This review addresses the concept that essential trace minerals play a vital role in many enzymatic and metabolic pathways that are critical for conceptus development during pregnancy in livestock species. The conceptus relies entirely on the maternal system for a sufficient supply of trace minerals and other nutrients needed for normal development. If this supply is inadequate, growth and/or health of the conceptus can be affected adversely, and many of these effects carry over into the neonatal period. Information, accumulated in our laboratory and presented herein, indicates that zinc, copper and manganese are among the trace minerals that have the greatest impact on reproduction. For example, levels of zinc, copper and manganese were several fold greater in the conceptus than in other reproductive tissues, indicating that the conceptus preferentially accumulates these minerals, an action that may be important for conceptus development, growth and survival. Moreover, some recent results indicate that increasing the biological availability of zinc, copper and manganese, by attachment to short peptide chains (i.e., proteinated trace minerals) can enhance reproductive performance of swine. Mineral concentrations in conceptuses from female pigs consuming proteinated trace minerals were greater than those from females that consumed only inorganic mineral salts. Elucidating the mechanisms whereby conceptus development and survival are enhanced by essential trace minerals may lead to development of specific feeding programs to increase the number and health of offspring at parturition, thereby allowing for further improvements in production efficiency in animal agriculture.

The role of essential trace elements in embryonic and fetal development in livestock.

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Embryonicsteroids and the establishment of pregnancy in pigs

Twenty prepuberal (P) gilts, 56.5 ± 1.1 kg body weight, were induced to ovulate with 1000 IU of pregnantmare’sserum gonadotropin followed 72 h later by 500 IU of human chorionic gonadotropin (hCG), and bred by artificial insemination (Al) with 50 ml fresh pooled boar semen the day after hCG treatment (Day 0). Eighteen mature (M) gilts, 120.6 ± 1.7 kg body weight, were bred by Al each day of estrus using pooled semen from the same boars (onset of estrus=Day 0). One-half of each group was fed the prostagiandin (PG) synthesis inhibitor indomethacin (IND), at 10 mg/kg body weight, or control (C) feed twice daily on Days 10 to 25. Blood samples taken by venipuncture on Days 10, 15,20 and 25 were quantitated for progesterone (P4) and 13,14-dihydro-15-ketoPGF� � (PGFM) by radioimmunoassay. Ovaries were examined on Day 26. All M-C guts were pregnant, whereas 3 of 9 M-IND gilts (P<0.05) and none of the P gilts (P<0.01) were pregnant. Three of the 6 nonpregnant M-IND gilts displayed estruson Day 21. The 3 remaining M-IND gilts had maintained corpora lutea (CL) on Day 26. Only corpora albicantia were present in P gilts on Day 26. Serum P4 concentrations for M-C gilts, nonpregnant M-IND gilts with maintained CL, and pregnant M-IND giltswere not different. Serum P4 for all nonpregnant gilts in which CL had regressedby Day 25 decreased to lessthan 5 ng/ml on Day 20.Serum PGFM concentrations on Days 15, 20 and 25 demonstrated that IND blockedPG synthesis. Therefore,inhibition of PG secretionfailedto protectCL from the luteolytic influence of the uterus and failed to allow maintenanceof pregnancy in P gilts. Pregnancy failure in 6 of 9 M-IND gifts indicates that PG production may be essential for establishment of pregnancy.

Nancy A. Fiorello

Papers

Inhibition of pregnancy with indomethacin in mature gilts and prepuberal gilts induced to ovulate.