T. H. Welsh

Phenotypic and genetic relationships of residual feed intake with performance and ultrasound carcass traits in Brangus heifers.

The objective of this study was to characterize residual feed intake (RFI) and to estimate phenotypic and genetic correlations with performance and ultrasound carcass traits in growing heifers. Four postweaning feed efficiency trials were conducted using 468 Brangus heifers. The complete Brangus pedigree file from Camp Cooley Ranch (Franklin, TX), which included 31,215 animals, was used to generate genetic parameter estimates. The heifer progeny from 223 dams were sired by 36 bulls, whereas the complete pedigree file contained 1,710 sires and 8,191 dams. Heifers were individually fed a roughage-based diet (ME = 1.98 Mcal/kg of DM) using Calan gate feeders for 70 d. Heifer BW was recorded weekly and ultrasound measures of 12th- to 13th-rib fat thickness (BF) and LM area (LMA) obtained at d 0 and 70. Residual feed intake (RFIp) was computed as actual minus predicted DMI, with predicted DMI determined by linear regression of DMI on mid-test BW(0.75) (MBW) and ADG with trial, trial x MBW, and trial x ADG as random effects. Overall means for ADG, DMI, and RFI were 1.01 (SD = 0.15), 9.51 (SD = 1.02), and 0.00 (SD = 0.71) kg/d, respectively. Stepwise regression analysis revealed that inclusion of gain in BF and final LMA into the base model increased the R(2) (0.578 vs. 0.534) and accounted for 9% of the variation in DMI not explained by MBW and ADG (RFIp). Residual feed intake and carcass-adjusted RFI (RFIc) were strongly correlated phenotypically and genetically with DMI and FCR, but not with ADG or MBW. Gain in BF was phenotypically correlated (P < 0.05) with RFIp (0.22), but not with FCR or RFIc; however, final BF was genetically correlated (P < 0.05) with RFIp (0.36) and RFIc (0.39). Gain in LMA was weakly phenotypically correlated with FCR, but not with RFIp or RFIc; however, gain in LMA was strongly genetically correlated with RFIp (0.55) and RFIc (0.77). The Spearman rank correlation between RFIp and RFIc was high (0.96). These results suggest that adjusting RFI for ultrasound carcass composition traits will facilitate selection phenotypically independent of growth, body size, and carcass composition; however, genetic relationships may still exist between RFI and carcass composition.

Normal development of thymus in male and female mice requires estrogen/estrogen receptor-α signaling pathway

Estrogen receptors (ERs) are expressed in the thymus of both males and females, but their role in thymic development and function is unclear. To determine whether ERα plays a role in thymic function of either males or females, we compared thymuses of male and female wild-type (WT) and ERα knockout (αERKO) mice from birth to adulthood. Although thymic size was similar in both male and female WT and αERKO mice at birth (d 0), by postnatal d 5 and at all subsequent ages, both male and female αERKO mice had significant (30–55%) reductions in thymic weight. Morphometric analysis revealed a reduction in thymic medullary areas in adult αERKO mice compared with age-matched WT controls that paralleled thymic involution. There were changes in relative percentages of CD4+ and CD4+CD8+ T-cells, and large decreases (70–80%) in overall absolute numbers of CD4+ and CD4+CD8+ T-cells. Serum corticosterone and testosterone levels were not different in either neonatal or adult male WT or αERKO mice, and serum levels of 17β-estradiol (E2) were similar in neonatal WT and αERKO males, indicating that increases in these thymolytic hormones are not responsible for the decreased thymic weight in αERKO males. Additionally, delayed-type hypersensitivity was significantly increased in male αERKO mice compared with WT mice. In summary, ERα deficiency does not inhibitinitial differentiation or fetal thymic development, but the absence of ERα results in marked decreases in thymic size in both sexes during the postnatal period. These results are the first direct demonstration that the E2/ERα signaling system is necessary for maintenance of normal postnatal function of the female thymus gland. The similar results obtained in males demonstrate a role for the E2/ERα signaling system in the male thymus and emphasize that estrogens play a more critical role in the male than previously realized.

The Effects of Restraint Stress on the Neuropathogenesis of Theiler's Virus Infection: I. Acute Disease

Restraint stress was found to have a profound effect on the acute phase of Theilers virus infection. Increased mortality rates were observed in restrained CBA mice infected with the BeAn strain of Theilers virus. In addition, restrained mice developed higher CNS viral titers than infected/nonrestrained mice. Thymic atrophy was observed in both infected and uninfected restrained mice. Decreased microgliosis, perivascular cuffing, and astrocytosis were observed in restrained mice compared to nonrestrained infected mice at 7 days postinfection. Restraint-stressed mice also developed decreased numbers of lymphocytes and increased numbers of neutrophils in the blood. The mechanism proposed for these alterations involves stress-induced corticosterone, which causes immunosuppression, decreased trafficking of inflammatory cells in the CNS, and, consequently, increased viral replication.

Chronic restraint stress during early Theiler's virus infection exacerbates the subsequent demyelinating disease in SJL mice.

Chronic restraint stress, administered during early infection with Theilers virus, was found to exacerbate the acute central nervous system (CNS) viral infection and the subsequent demyelinating phase of disease (an animal model of Multiple Sclerosis (MS)) in SJL male and female mice. During early infection, stressed mice displayed decreased body weights and spontaneous activity; while increased behavioral signs of illness and plasma corticosterone (CORT) levels. During the subsequent chronic demyelinating phase of disease, previously stressed mice had greater behavioral signs of the chronic phase, worsened rotarod performance, and increased inflammatory lesions of the spinal cord. In addition, mice developed autoantibodies to myelin basic protein (MBP), proteolipid protein peptide (PLP139-151), and myelin oligodendrocyte glycoprotein peptide (MOG33-55).

Social stress alters the severity of acute Theiler's virus infection

Our laboratory has previously shown that restraint stress resulted in decreased Theilers virus-induced CNS inflammation, while exacerbating illness behaviors during the acute phase of disease. In contrast, social disruption stress (SDR) applied prior to infection led to the development of glucocorticoid (GC) resistance, and these animals developed more severe disease course, with increased inflammation. However, when SDR was applied concurrent with infection, GC resistance fails to develop, disease course is less severe and inflammation was moderate. These results suggest that the effects of SDR on Theilers virus infection are dependent upon the timing of SDR application in relation to infection.

Leptin acts at the bovine adenohypophysis to enhance basal and gonadotropin-releasing hormone-mediated release of luteinizing hormone : differential effects are dependent upon nutritional history

Abstract Recombinant ovine leptin (oleptin) stimulates an acute increase in the secretion of LH in fasted, but not in normal-fed, cows through an augmentation of the magnitude of individual pulses of LH. Herein, we tested the hypothesis that this effect could be accounted for by functional changes at the adenohypophyseal (AP) level. Eleven ovariectomized, estradiol-implanted cows were assigned to one of two dietary groups: normal-fed (n = 6) and fasted (fasted for 72 h; n = 5). After the animals were killed, the adenohypophyses were collected and AP explants were perifused with Krebs-Ringer bicarbonate buffer (KRB) for a total of 6.5 h, including a 2-h treatment at 2.5 h with KRB or increasing doses of oleptin and a challenge at 4.5 h with 50 ng of GnRH. To test for effects of leptin at the hypothalamic level, explants encompassing the medial basal hypothalamus-infundibular complex (HYP) were incubated in KRB alone (control) or in KRB containing 1000 ng of oleptin. Basal release of LH from AP explants treated with leptin was greater (P < 0.02) than that from control-treated explants in fasted, but not in normal-fed, cows. To the contrary, leptin-treated explants from normal-fed, but not from fasted, cows released more (P < 0.001) LH in response to GnRH than control-treated tissues. Neither fasting nor leptin affected (P > 0.1) the secretion of GnRH from HYP explants. These observations support the hypothesis that leptin modulates the secretion of LH in mature cows, to a large extent, by its direct actions at the AP. Differential manifestations of these effects are dependent upon nutritional history.

The effects of restraint stress on the neuropathogenesis of Theiler’s virus infection II: NK cell function and cytokine levels in acute disease

Psychological stress is thought to play an important role in multiple sclerosis. We have been investigating the role of restraint stress in Theilers virus infection in mice as a model for multiple sclerosis. We have previously determined that restraint stressed CBA mice had higher levels of mortality following infection with Theilers virus. We proposed that this was due to high levels of stress-induced corticosterone, which resulted in decreased numbers of circulating lymphocytes, decreased inflammatory cell infiltrates into the brain and consequently decreased viral clearance from the central nervous system (CNS). The effect of restraint stress on the innate immune response to Theilers virus is further investigated in the current study. Restraint stressed mice developed clinical signs of encephalitis, thymic atrophy, and adrenal hypertrophy. Decreased numbers of circulating lymphocytes and increased numbers of neutrophils were observed in the stressed mice. Stressed mice also had lower numbers of spleen cells which correlated with the decreased numbers of lymphocytes in circulation. Restraint stress caused elevations in serum tumor necrosis alpha (TNF-alpha). Virus-induced natural killer cell (NK) cytotoxic activity was significantly reduced in restrained mice at one day post infection which may account for the reduced viral clearance from the CNS. These data suggest that stress-induced immunosuppression of cytolytic NK cell activity may account in part for the reduced ability to clear virus from the CNS and increased mortality observed in this model.

HSD11B1, HSD11B2, PTGS2, and NR3C1 Expression in the Peri-Implantation Ovine Uterus: Effects of Pregnancy, Progesterone, and Interferon Tau

Abstract Establishment of pregnancy in ruminants requires conceptus elongation and production of interferon tau (IFNT), the pregnancy recognition signal that maintains the corpus luteum and progesterone (P4) secretion. The enzymes hydroxysteroid (11-beta) dehydrogenase 1 (HSD11B1) and HSD11B2 catalyze the interconversion of inactive cortisone and active cortisol, which is a biologically active glucorticoid and ligand for the receptor subfamily 3, group C, member 1 (glucocorticoid receptor) (NR3C1). The activity of HSD11B1 is stimulated by P4, prostaglandins, and cortisol. These studies determined the effects of pregnancy, P4, and IFNT on HSD11B1, HSD11B2, prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) (PTGS2), and nuclear NR3C1 in the ovine uterus. Endometrial HSD11B1 mRNA levels were more abundant between Days 12 and 16 of pregnancy than the estrous cycle, and HSD11B1 and PTGS2 expression in the endometrial luminal and superficial glandular epithelia was coincident with conceptus elongation. HSD11B1 mRNA was very low in the conceptus, whereas HSD11B2 mRNA was abundant in the conceptus but not in the uterus. Treatment of ewes with P4 induced, and intrauterine infusions of IFNT modestly stimulated, HSD11B1 expression in the endometrial luminal and superficial glandular epithelia. In all of the studies, HSD11B1 and PTGS2 expression was coincident in the endometrial epithelia, and NR3C1 was present in all endometrial cell types. Collectively, these results support hypotheses that endometrial epithelial HSD11B1 expression is induced by P4 as well as stimulated by IFNT and PTGS2-derived prostaglandins and that HSD11B1-regenerated cortisol acts via NR3C1 to regulate ovine endometrial functions during early pregnancy.

Temporal pattern and effect of sex on lipopolysaccharide-induced stress hormone and cytokine response in pigs

The temporal pattern and sex effect of immune and stress hormone responses to a lipopolysaccharide (LPS) challenge were assessed using a pig model. Secretion of the pro-inflammatory cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 increased in a time-dependent manner following LPS infusion. There was also a time-dependent increase in secretion of the stress-related hormones cortisol, epinephrine (E), and norepinephrine (NE) following LPS, with peak concentrations attained within 30 min. The magnitude of the TNF-alpha and IL-1beta responses were both positively associated (P < 0.05) with the magnitude of cortisol response following LPS, whereas serum IL-1beta and IL-6 were positively correlated with the magnitude of E and NE responses following LPS. Acute-phase protein production was also time-dependently increased following LPS. The concentration of immune cells in circulation was decreased (P < 0.05) at 5.5h post-LPS and negatively correlated with pro-inflammatory cytokine production. By 24h post-LPS, immune cell counts increased (P < 0.05) and were positively associated with both pro-inflammatory cytokine and stress hormone production. The amplitude of pro-inflammatory cytokine response following LPS was affected (P < 0.05) by sex classification; however, the magnitude of elevated cytokine concentrations was not. The magnitude of the NE response, but not of the E and cortisol responses, to LPS was influenced by sex (P < 0.05). Similar to the pro-inflammatory cytokines, the magnitude of exposure to the stress hormones following LPS was not influenced by sex. The production of serum amyloid A (SAA) was influenced by sex, with barrows producing more SAA than gilts at 24h post-LPS (P < 0.05). Collectively, these results demonstrate sex-specific, concomitant temporal changes in innate immune- and stress-related hormones.

Estrogen and Antiestrogen Effects on Neonatal Ovine Uterine Development

Abstract Postnatal development of the ovine uterus between birth and Postnatal Day (PND) 56 involves differentiation of the endometrial glandular epithelium from the luminal epithelium followed by tubulogenesis and branching morphogenesis. These critical events coincide with expression of estrogen receptor α (ERα) by nascent endometrial glands and stroma. To test the working hypothesis that estrogen and uterine ERα regulate uterine growth and endometrial gland morphogenesis in the neonatal ewe, ewes were treated daily from birth (PND 0) to PND 55 with 1) saline and corn oil as a vehicle control (CX), 2) estradiol-17β (E2) valerate (EV), an ERα agonist, 3) EM-800, an ERα antagonist, or 4) CGS 20267, a nonsteroidal aromatase inhibitor. On PND 14, ewes were hemihysterectomized, and the ipsilateral oviduct and ovary were removed. The remaining uterine horn, oviduct, and ovary were removed on PND 56. Treatment with CGS 20267 decreased plasma E2 levels, whereas EM-800 had no effect compared with CX ewes. Uterine horn weight and length were not affected by EM-800 or CGS 20267 but were decreased in EV ewes on PND 56. On PND 14 and PND 56, treatment with EV decreased endometrial thickness but increased myometrial thickness. The numbers of ductal gland invaginations and endometrial glands were not affected by CGS but were lower in EM-800 ewes on PND 56. Exposure to EV completely inhibited endometrial gland development and induced luminal epithelial hypertrophy but did not alter uterine cell proliferation. Exposure to EV substantially decreased expression of ERα, insulin-like growth factor (IGF) I, and IGF-II in the endometrium. Results indicate that circulating E2 does not regulate endometrial gland differentiation or development. Although ERα does not regulate initial differentiation of the endometrial glandular epithelium, results indicate that ERα does regulate, in part, coiling and branching morphogenesis of endometrial glands in the neonatal ewe. Ablation of endometrial gland genesis by EV indicates that postnatal uterine development is extremely sensitive to the detrimental effects of inappropriate steroid exposure.