Troy L. Ott

Interferon Tau: A Novel Pregnancy Recognition Signal

PROBLEM: Trophectoderm of ruminant conceptuses (embryo and associated membranes) secretes tau interferons (IFNẗ) as the pregnancy recognition signal. How does it act?

Ovine Uterine Gland Knock-Out Model: Effects of Gland Ablation on the Estrous Cycle

Abstract Ovine endometrial gland development is a postnatal event that can be inhibited epigenetically by chronic exposure of ewe lambs to a synthetic progestin from birth to puberty. As adults, these neonatally progestin-treated ewes lack endometrial glands and display a uterine gland knockout (UGKO) phenotype that is useful as a model for study of endometrial function. Here, objectives were to determine: 1) length of progestin exposure necessary from birth to produce the UGKO phenotype in ewes; 2) if UGKO ewes display normal estrous cycles; and 3) if UGKO ewes could establish and/or maintain pregnancy. Ewe lambs (n = 22) received a Norgestomet (Nor) implant at birth and every two weeks thereafter for 8 (Group I), 16 (Group II), or 32 (Groups III and IV) weeks. Control ewe lambs (n = 13) received no Nor treatment (Groups V and VI). Ewes in Groups I, II, III, and VI were hemihysterectomized (Hhx) at 16 weeks of age. After puberty, the remaining uterine horn in Hhx ewes was removed on either Day 9 or 15 of the estrous cycle (Day 0 = estrus). Histological analyses of uteri indicated that progestin exposure for 8, 16, or 32 weeks prevented endometrial adenogenesis and produced the UGKO phenotype in adult ewes. Three endometrial phenotypes were consistently observed in Nor-treated ewes: 1) no glands, 2) slight glandular invaginations into the stroma, and 3) limited numbers of cyst- or gland-like structures in the stroma. Overall patterns of uterine progesterone, estrogen, and oxytocin receptor expression were not different in uteri from adult cyclic control and UGKO ewes. However, receptor expression was variegated in the ruffled luminal epithelium of uteri from UGKO ewes. Intact UGKO ewes displayed altered estrous cycles with interestrous intervals of 17 to 43 days, and they responded to exogenous prostaglandin F2∝ (PGF) with luteolysis and behavioral estrus. During the estrous cycle, plasma concentrations of progesterone in intact control and UGKO ewes were not different during metestrus and diestrus, but levels did not decline in many UGKO ewes during late diestrus. Peak peripheral plasma concentrations of PGF metabolite, in response to an oxytocin challenge on Day 15, were threefold lower in UGKO compared to control ewes. Intact UGKO ewes bred repeatedly to intact rams did not display evidence of pregnancy based on results of ultrasound. Collectively, results indicate that 1) transient, progestin-induced disruption of ovine uterine development from birth alters both structural and functional integrity of the adult endometrium; 2) normal adult endometrial integrity, including uterine glands, is required to insure a luteolytic pattern of PGF production; and 3) the UGKO phenotype, characterized by the absence of endometrial glands and a compact, disorganized endometrial stroma, limits or inhibits the capacity of uterine tissues to support the establishment and/or maintenance of pregnancy.

Special topics--Mitigation of methane and nitrous oxide emissions from animal operations: III. A review of animal management mitigation options.

The goal of this review was to analyze published data on animal management practices that mitigate enteric methane (CH4) and nitrous oxide (N2O) emissions from animal operations. Increasing animal productivity can be a very effective strategy for reducing greenhouse gas (GHG) emissions per unit of livestock product. Improving the genetic potential of animals through planned cross-breeding or selection within breeds and achieving this genetic potential through proper nutrition and improvements in reproductive efficiency, animal health, and reproductive lifespan are effective approaches for improving animal productivity and reducing GHG emission intensity. In subsistence production systems, reduction of herd size would increase feed availability and productivity of individual animals and the total herd, thus lowering CH4 emission intensity. In these systems, improving the nutritive value of low-quality feeds for ruminant diets can have a considerable benefit on herd productivity while keeping the herd CH4 output constant or even decreasing it. Residual feed intake may be a tool for screening animals that are low CH4 emitters, but there is currently insufficient evidence that low residual feed intake animals have a lower CH4 yield per unit of feed intake or animal product. Reducing age at slaughter of finished cattle and the number of days that animals are on feed in the feedlot can significantly reduce GHG emissions in beef and other meat animal production systems. Improved animal health and reduced mortality and morbidity are expected to increase herd productivity and reduce GHG emission intensity in all livestock production systems. Pursuing a suite of intensive and extensive reproductive management technologies provides a significant opportunity to reduce GHG emissions. Recommended approaches will differ by region and species but should target increasing conception rates in dairy, beef, and buffalo, increasing fecundity in swine and small ruminants, and reducing embryo wastage in all species. Interactions among individual components of livestock production systems are complex but must be considered when recommending GHG mitigation practices.

Mitigation of methane and nitrous oxide emissions from animal operations: III. A review of animal management mitigation options

This review analyzes published data on manure management practices used to mitigate methane (CH4) and nitrous oxide (N2O) emissions from animal operations. Reducing excreted nitrogen (N) and degradable organic carbon (C) by diet manipulation to improve the balance of nutrient inputs with production is an effective practice to reduce CH4 and N2O emissions. Most CH4 is produced during manure storage; therefore, reducing storage time, lowering manure temperature by storing it outside during colder seasons, and capturing and combusting the CH4 produced during storage are effective practices to reduce CH4 emission. Anaerobic digestion with combustion of the gas produced is effective in reducing CH4 emission and organic C content of manure; this increases readily available C and N for microbial processes creating little CH4 and increased N2O emissions following land application. Nitrous oxide emission occurs following land application as a byproduct of nitrification and dentrification processes in the soil, but these processes may also occur in compost, biofilter materials, and permeable storage covers. These microbial processes depend on temperature, moisture content, availability of easily degradable organic C, and oxidation status of the environment, which make N2O emissions and mitigation results highly variable. Managing the fate of ammoniacal N is essential to the success of N2O and CH4 mitigation because ammonia is an important component in the cycling of N through manure, soil, crops, and animal feeds. Manure application techniques such as subsurface injection reduce ammonia and CH4 emissions but can result in increased N2O emissions. Injection works well when combined with anaerobic digestion and solids separation by improving infiltration. Additives such as urease and nitrification inhibitors that inhibit microbial processes have mixed results but are generally effective in controlling N2O emission from intensive grazing systems. Matching plant nutrient requirements with manure fertilization, managing grazing intensity, and using cover crops are effective practices to increase plant N uptake and reduce N2O emissions. Due to system interactions, mitigation practices that reduce emissions in one stage of the manure management process may increase emissions elsewhere, so mitigation practices must be evaluated at the whole farm level.

τ-Interferon: Pregnancy Recognition Signal in Ruminants

Summary The ovine uterus provides an excellent in vivo model system for the study of the cellular and molecular mechanisms of Type I IFN and steroid hormone regulation of hormone receptor gene expression in an epitheliomesenchymal organ. Future experiments will be directed toward determining the signal transduction pathway activated by IFN-τ and mechanisms involved in regulation of gene expression. These experiments include (i) cloning the Type I IFN receptor found on the endometrial luminal and superficial glandular epithelium; (ii) eluciding the signal transduction pathway activated by IFN-τ binding to the Type I IFN receptor; (iii) cloning and structural analysis of the ovine ER and OTR genes; (iv) determining mechanisms regulating transcription of the ovine ER and OTR genes, particularly those involving both IFN-τ and progesterone; (v) determining the role(s) of IFN-τ-induced proteins (e.g., Mx protein) in establishment of pregnancy; and (vi) investigating conceptus-endometrial and epithelial-stromal interactions that integrate and coordinate endometrial physiology during the estrous cycle and pregnancy.

Pregnancy recognition in ruminants, pigs and horses: Signals from the trophoblast

Abstract Interferon tau (IFNτ), secreted by trophectoderm of sheep, cow and goat conceptuses (embryo and associated membranes), is the pregnancy recognition signal. The 172 AA mature IFNτ protein with conserved cysteine residues at positions 1, 29, 99 and 139 is a unique and largely uncharacterized subclass of Type I interferon. Interferon tau, the paracrine antiluteolytic signal, acts on uterine epithelium to prevent pulsatile release of PGF2α and insure maintenance of a functional corpus luteum. Secretion of IFNτ is limited to early pregnancy, with Days 12–13 for sheep and Days 14–17 for cows and goats being critical for pregnancy recognition. Secretion of ovine (o) IFNτ is stimulated by granulocyte monocyte/macrophage colony stimulating factor (GM-CSF) or insulin-like growth factors I and II combined suggesting that uterine factors influence IFNτ gene expression. There are few uterine receptors for oxytocin (OTR) or estrogen (ER) in early pregnant ewes or after intrauterine injections of oIFNτ, so pulsatile release of PGF required for luteolysis is abrogated. Ovine IFNτ may stabilize progesterone receptors (PR) to inhibit up-regulation of ER and OTR in uterine epithelium to prevent luteolysis; an effect likely mediated by IFN-stimulated response elements in the receptor genomic DNA. Pig conceptuses secrete both IFNα (25%) and IFNγ (75%) between Days 15 and 21 of gestation, but their roles in early pregnancy are unknown. Inhibition of secretion of luteolytic PGF in pigs is in response to estrogens of blastocyst origin which induce upregulation of endometrial receptors for prolactin. Effects of prolactin and estrogen may be influenced by IFNα and/or IFNγ from pig trophoblast. The equine conceptus may signal pregnancy recognition through secretion of a low molecular weight protein, estrogen and/or PGE, but the precise signal and its mechanism of action have not been elucidated.

Endocrinology of the Transition from Recurring Estrous Cycles to Establishment of Pregnancy in Subprimate Mammals

Pregnancy is established and maintained in subprimate mammals in response to a series of interactions among the conceptus (embryo and associated membranes), uterus, and/or ovarian corpus luteum (CL). These interactions prevent functional and structural regression of the CL, or luteolysis. This chapter describes aspects of the endocrinology of recurring estrous cycles in ruminants, swine, horses, cats, dogs, and rodents, but the primary focus is on signaling for maternal recognition of pregnancy. During the peri-implantation period, pregnancy recognition signals from the conceptus to the maternal system are anti-luteolytic and/or luteotrophic. The functional life-span of the CL is controlled by release of prostaglandin F2α (PGF) from the uterus and/or ovaries, whereas pregnancy recognition signals from the trophoblast may act in a paracrine or endocrine manner to interrupt endometrial or intraovarian production of luteolytic PGF (antiluteolytic) or the effect may be directly on the CL (luteotropic). The primary focus of this chapter is pregnancy recognition signals in subprimate mammals, which prevent luteolysis and ensure maintenance of an intrauterine environment that supports events associated with establishment and maintenance of pregnancy.

Natural killer cell activity of lymphocytes exposed to ovine, type I, trophoblast interferon

PROBLEM: A member of newly described interferon (IFN) family, ovine trophoblast protein one (oTP‐1, now named as ovine type I trophoblast interferon, oTIFN), is a major secretory product of sheep conceptuses during days 11–21 of pregnancy. Type I trophoblast IFN shares high amino acid and nucleotide sequence homology with other mammalian IFN‐αs and has functional characteristics of IFNs such as antiproliferative, immunosuppressive, and antiviral activities. Moreover, oTIFN is responsible for the antiluteolytic signaling for early pregnancy recognition in sheep. It has been reported that natural killer (NK) cells are recruited to the pregnant uterus and contribute para‐immunotrophic effects on growth and differentiation of the conceptus (embryo/fetus and associated membranes). Because IFNs are potent modulators of NK cell activity, the present study examined interactions between oTIFN and sheep and pig NK cells.

Effects of Early Conceptus Signals on Circulating Immune Cells: Lessons from Domestic Ruminants

Citation Ott TL, Gifford CA. Effects of early conceptus signals on circulating immune cells: lessons from domestic ruminants. Am J Reprod Immunol 2010

Low Doses of Bovine Somatotropin Enhance Conceptus Development and Fertility in Lactating Dairy Cows

ABSTRACT Objectives were to evaluate the effects of administering either one or two low doses of slow-release recombinant bovine somatotropin (bST) on hormone concentrations, conceptus development, and fertility in dairy cows. Cows from two farms were detected in estrus on or after 50 days postpartum (n = 1483), inseminated, and enrolled in the study (Day 0). Within farm, cows were blocked by parity and assigned randomly to receive a single placebo injection at insemination (control), a single injection with 325 mg of bST at insemination (S-bST), or two injections with 325 mg of bST administered on Days 0 and 14 (T-bST). From a subset of cows, blood was collected twice weekly from Day 0 to 42 for determination of hormone concentrations and on Day 19 for isolation of leucocytes and analysis of transcript abundance of selected interferon-stimulated genes. Pregnancy was diagnosed on Days 31 and 66, and ultrasonographic morphometry of the conceptus was performed on Days 34 and 48 in a subset of cows. Cows that received T-bST had increased plasma concentrations of GH and IGF1 for 4 wk, increased mRNA expression of ISG15 and RTP4 in leukocytes, earlier rise in the pregnancy-specific protein B in plasma of pregnant cows, increased conceptus size, and enhanced fertility. Cows that received S-bST had increased concentrations of GH and IGF1 for only 2 wk and it was insufficient to alter conceptus development and fertility. In conclusion, supplementation with low doses of bST during the pre- and peri-implantation periods enhanced conceptus development, reduced embryonic losses, and improved fertility in dairy cows.