Ovine Pregnancy Research Articles

Interferon-τ: Current Applications and Potential in Antiviral Therapy

Interferon-tau (IFN-tau) was initially identified as an ovine pregnancy protein. Produced by the trophoblast, it is important in preventing degradation of the corpus luteum and has been used as an early marker for ovine pregnancy. As a member of the family of type I interferons, IFN-tau has demonstrated promising antiviral activity against human viral infections in vitro. Additionally, it displays high species cross-reactivity despite its absence in humans. To date, IFN-tau has shown efficacy in reducing replication of human immunodeficiency virus, feline immunodeficiency virus, and human papillomavirus. While IFN-tau shares similar antiviral activity to IFN-alpha, the current interferon of choice for treatment of viral infections, it lacks the associated toxicity. This may make IFN-tau an attractive alternative to IFN-alpha for the treatment of viral infections.

γδTCR+ cells of the pregnant ovine uterus express variable T cell receptors and contain granulysin

Gammadelta T cells are a prominent granulated cell population in the ruminant pregnant uterus and both their number and granule size increase dramatically during pregnancy. Anchor-RT-PCR was used to assess TCRdelta gene usage by gammadelta T cells from the uterine epithelium of pregnant sheep. The TCRdelta genes obtained exhibited distinct combinatorial and junctional diversity and only two out of nine V-D-J rearrangements sequenced were identical. Furthermore, two of the Vdelta elements used are also expressed in peripheral blood, indicating that gammadeltaTCR use in sheep epithelia is neither restricted nor site-specific, similar to humans but in contrast to findings in mice. Protein analysis of purified, granulated uterine gammadelta T cells revealed the presence of large amounts of the antimicrobial peptide, granulysin. The results of the present study indicate that ovine uterine gammadeltaTCR(+) intraepithelial lymphocytes have the potential to recognise diverse antigens and may have a role in protecting the uterus from infection during pregnancy and parturition. A similar protective role for gammadelta T cells may exist in the human decidua parietalis.

Local Factors of Placentation Substantially Alter Uterine Artery Structural and Mechanical Indices, Vascular Impedance Metrics, and eNOS Levels During Ovine Pregnancy.

Local Factors of Placentation Substantially Alter Uterine Artery Structural and Mechanical Indices, Vascular Impedance Metrics, and eNOS Levels During Ovine Pregnancy.

Effect of Gravidity on Uterine Blood Flows Relative to Structural and Mechanical Indices of Remodeling in Uterine Arteries During the Ovine Ovarian Cycle vs. Pregnancy.

Effect of Gravidity on Uterine Blood Flows Relative to Structural and Mechanical Indices of Remodeling in Uterine Arteries During the Ovine Ovarian Cycle vs. Pregnancy.

Pregnancy modifies the large conductance Ca2+-activated K+ channel and cGMP-dependent signaling pathway in uterine vascular smooth muscle

Regulation of uteroplacental blood flow (UPBF) during pregnancy remains unclear. Large conductance, Ca(2+)-activated K(+) channels (BK(Ca)), consisting of alpha- and regulatory beta-subunits, are expressed in uterine vascular smooth muscle (UVSM) and contribute to the maintenance of UPBF in the last third of ovine pregnancy, but their expression pattern and activation pathways are unclear. We examined BK(Ca) subunit expression, the cGMP-dependent signaling pathway, and the functional role of BK(Ca) in uterine arteries (UA) from nonpregnant (n = 7), pregnant (n = 38; 56-145 days gestation; term, approximately 150 days), and postpartum (n = 15; 2-56 days) sheep. The alpha-subunit protein switched from 83-87 and 105 kDa forms in nonpregnant UVSM to 100 kDa throughout pregnancy, reversal occurring >30 days postpartum. The 39-kDa beta(1)-subunit was the primary regulatory subunit. Levels of 100-kDa alpha-subunit rose approximately 70% during placentation (P < 0.05) and were unchanged in the last two-thirds of pregnancy; in contrast, beta(1)-protein rose throughout pregnancy (R(2) = 0.996; P < 0.001; n = 13), increasing 50% during placentation and approximately twofold in the remainder of gestation. Although UVSM soluble guanylyl cyclase was unchanged, cGMP and protein kinase G(1alpha) increased (P < 0.02), paralleling the rise and fall in beta(1)-protein during pregnancy and the puerperium. BK(Ca) inhibition not only decreased UA nitric oxide (NO)-induced relaxation but also enhanced alpha-agonist-induced vasoconstriction. UVSM BK(Ca) modify relaxation-contraction responses in the last two-thirds of ovine pregnancy, and this is associated with alterations in alpha-subunit composition, alpha:beta(1)-subunit stoichiometry, and upregulation of the cGMP-dependent pathway, suggesting that BK(Ca) activation via NO-cGMP and beta(1) augmentation may contribute to the regulation of UPBF.

Enhanced focal adhesion assembly reflects increased mechanosensation and mechanotransduction at maternal–conceptus interface and uterine wall during ovine pregnancy

The integrity of the fetal-maternal interface is critical for proper fetal nourishment during pregnancy. Integrins are important adhesion molecules present at the interface during implantation; however, in vivo evidence for integrin activation and focal adhesion formation at the maternal-conceptus interface is limited. We hypothesized that focal adhesion assembly in uterine luminal epithelium (LE) and conceptus trophectoderm (Tr) results from integrin binding of extracellular matrix (ECM) at this interface to provide increased tensile forces and signaling to coordinate utero-placental development. An ovine model of unilateral pregnancy was used to evaluate mechanotransduction events leading to focal adhesion assembly at the maternal-conceptus interface and within the uterine wall. Animals were hysterectomized on days 40, 80, or 120 of pregnancy, and uteri immunostained for integrins (ITGAV, ITGA4, ITGA5, ITGB1, ITGB3, and ITGB5), ECM proteins (SPP1, LGALS15, fibronectin (FN), and vitronectin (VTN)), cytoskeletal molecules (ACTN and TLN1), and a signal generator (PTK2). Focal adhesion assembly in myometrium and stroma was also studied to provide a frame of reference for mechanical stretch of the uterine wall. Large focal adhesions containing aggregates of ITGAV, ITGA4, ITGA5, ITGB1, ITGB5, ACTN, and PTK2 were detected in interplacentomal uterine LE and Tr of gravid but not non-gravid uterine horns and increased during pregnancy. SPP1 and LGALS15, but not FN or VTN, were present along LE and Tr interfaces in both uterine horns. These data support the idea that focal adhesion assembly at the maternal-conceptus interface reflects adaptation to increasing forces caused by the growing fetus. Cooperative binding of multiple integrins to SPP1 deposited at the maternal-conceptus interface forms an adhesive mosaic to maintain a tight connection between uterine and placental surfaces along regions of epitheliochorial placentation in sheep.

Regulation of maternal ACTH in ovine pregnancy: does progesterone play a role?

Pregnancy is characterized by increased plasma adrenocorticotropic hormone (ACTH) and cortisol. Studies suggest that progesterone acts as an antagonist at mineralocorticoid receptors. Therefore, we tested the hypothesis that chronic progesterone, produced by treatment of nonpregnant ewes or during pregnancy, will result in increased plasma ACTH relative to the plasma cortisol concentrations. We studied three groups of ewes: ovariectomized nonpregnant, nonpregnant treated with progesterone, and pregnant ewes. In two series of studies, ewes were adrenalectomized and replaced with 0.35 mg x kg(-1) x day(-1) or 0.5 mg x kg(-1) x day(-1) cortisol. In both studies, aldosterone was infused at 3 microg x kg(-1) x day(-1). In the first study, additional infusions of cortisol over 24 h were used to increase daily replacement doses to 0.5, 1, or 1.5 mg x kg(-1) x day(-1), and intact pregnant and nonpregnant ewes were studied with infusions of cortisol at 0, 0.5, and 1 mg x kg(-1) x day(-1). In adrenalectomized ewes chronically replaced to 0.35 mg x kg(-1) x day(-1) cortisol, plasma ACTH concentrations were decreased significantly in the nonpregnant progesterone-treated ewes compared with the ovariectomized nonpregnant ewes. With 0.5 mg x kg(-1) x day(-1) cortisol, plasma ACTH levels were greater in pregnant ewes than in nonpregnant ewes with or without progesterone. Overall plasma ACTH levels at 0.35 mg x kg(-1) x day(-1) were significantly related to the plasma protein concentration, suggesting that the ACTH levels in the hypocorticoid ewes are most closely related to plasma volume. Across all steroid doses, ACTH was positively related to plasma proteins and progesterone, and negatively related to cortisol. We conclude that increased progesterone does not alter the feedback relation of cortisol to ACTH, but may modulate ACTH indirectly through plasma volume.

Effects of twin pregnancy and periconceptional undernutrition on maternal metabolism, fetal growth and glucose–insulin axis function in ovine pregnancy

Although twins have lower birthweights than singletons, they may not experience the increased disease risk in adulthood reportedly associated with low birthweight. In contrast, another periconceptional event, maternal undernutrition, does not reduce birthweight but does affect fetal and postnatal physiology in sheep. We therefore studied maternal and fetal metabolism, growth and glucose-insulin axis function in late gestation in twin and singleton sheep pregnancies, either undernourished from 60 days before until 30 days after conception or fed ad libitum. We found that twin-bearing ewes had decreased maternal food intake in late gestation and lower maternal and fetal plasma glucose and insulin levels. Twin fetuses had fewer everted placentomes, grew slower in late gestation, and had a greater insulin response to a glucose challenge, but lesser response to arginine. In contrast, periconceptional undernutrition led to increased maternal food intake and a more rapid fall in maternal glucose levels in response to fasting. Periconceptional undernutrition increased the number of everted placentomes, and abolished the difference in insulin responses to glucose between twins and singletons. Thus, the physiology of twin pregnancy is quite different from that of singleton pregnancy, and is probably determined by a combination of factors acting in both early and late gestation. The inconsistency of the relationships between low birthweight and postnatal disease risk of twins may lie in their very different fetal development. These data suggest that twin pregnancy may be another paradigm of developmental programming, and indicate that twins and singletons must be examined separately in any study of fetal or postnatal physiology.

Periconceptional nutrition, twinning and how this impacts on current understanding of the aetiology and pathophysiology of the metabolic syndrome

Periconceptional nutrition, twinning and how this impacts on current understanding of the aetiology and pathophysiology of the metabolic syndrome

Effects of Twinning and Periconceptional Undernutrition on Late-Gestation Hypothalamic-Pituitary-Adrenal Axis Function in Ovine Pregnancy

The relationships between reduced size at birth, increased activity of the hypothalamic-pituitary-adrenal (HPA) axis, and increased risk of disease in adulthood are well described in singletons but are much less clear in twins. This may be because the physiological processes underlying reduced size at birth are different in singletons and twins. Periconceptional undernutrition can cause altered activity of the fetal and postnatal HPA axis without altering size at birth. However, the independent effects of periconceptional undernutrition and twinning on activity of the maternal and fetal HPA axes are not well described. We therefore studied maternal and fetal HPA axis function during late gestation in twin and singleton sheep pregnancies, either undernourished around conception or fed ad libitum. We found that twinning led to suppressed baseline HPA axis function and decreased adrenal sensitivity to ACTH stimulation but increased fetal pituitary ACTH response both to direct stimulation by CRH (ACTH area under the curve response: 29.7 +/- 2.2 vs. 17.1 +/- 1.6 ng/min x ml, P < 0.01) and to decreased cortisol negative feedback. In contrast, periconceptional undernutrition resulted in a decreased pituitary response (ACTH area under the curve response: 19.4 +/- 1.6 vs. 26.1 +/- 2.2 ng/min x ml, P = 0.02) but no difference in adrenal response. Thus, the HPA axis function of twin sheep fetuses in late gestation is very different from that of control and undernourished singletons. If the HPA axis is an important mediator between fetal adaptations and adult disease, these data may help explain why the relationship between fetal growth and postnatal physiology and disease risk is inconsistent in twins.

Evidence that primary infection of Charollais sheep withToxoplasma gondiimay not prevent foetal infection and abortion in subsequent lambings

A study carried out on a sheep farm examined whether Toxoplasma gondii foetal infection and associated abortion occur in successive lambings. We identified 29 ewes that gave birth to lambs on at least 2 successive years over our study period, 2000-2003. Tissue samples from the progeny of these ewes were analysed by PCR to determine infection status with T. gondii. T. gondii-infected lambs were born in 31% of successive pregnancies. T. gondii-positive lambs were aborted in successive pregnancies in 21% of lambings during study period, 2000-2003. The frequency of successive abortions within this flock over the period 1992-2003 was 18%. If a lamb was congenitally infected there was a high risk (69%) that the successive lamb from that ewe would also be congenitally infected. Similarly, if a lamb was aborted there was a high risk (55%) of abortion in the next lamb produced. These data suggest that life-long immunity to T. gondii infections may not always be acquired following an initial infection and raises the question as to whether the mechanisms of T. gondii transmission prior to and during ovine pregnancies are fully understood.

Ontogeny of endothelial nitric oxide synthase mRNA in an ovine model of fetal and placental growth restriction

To determine: 1) placental eNOS mRNA concentration across gestation in normal ovine pregnancy and in an ovine model of intrauterine growth restriction (IUGR), and 2) placental eNOS protein concentration in early ovine pregnancy. A total of 24 sheep were studied with 12 ewes placed in hyperthermic (HT) conditions to induce IUGR and 12 were kept in control conditions. HT and control animals underwent euthanasia at 3 developmental time points (55, 95, & 130 days gestational age; dGA) in ovine placental & fetal development. Compared to controls, HT pregnancies showed 1) no differences in fetal weights at 55 dGA and 95dGA with significant reductions at 130 dGA, 2) significantly smaller placentae at 95 and 130 dGA with a trend for a reduction at 55 dGA, 3) significant decreases in cotyledon eNOS mRNA at 95 and 130 dGA, 4) a significant increase in caruncle eNOS mRNA expression at 130 dGA, 5) significant increase in eNOS protein in the caruncle, but not in the cotyledon at 55 dGA. Placental eNOS concentration is transcriptionally regulated at mid-gestation, while additional post-transcriptional regulation is also involved during early and late gestation in this model of placental and fetal growth restriction.

Activated complement molecules mediate abnormal vasoreactivity of maternal and fetal arteries in an ovine model of fetal growth restriction

Evidence exists for a role for activated complement molecules (ACM) in fetal growth restriction (FGR). We hypothesized that maternal and fetal arteries from FGR ovine pregnancies would demonstrate increased sensitivity to ACM compared to control vessels.

Large-Conductance Ca2+-Dependent K+ Channels Regulate Basal Uteroplacental Blood Flow in Ovine Pregnancy

The mechanisms regulating basal uteroplacental blood flow (UBF) and the greater than 30-fold increase observed in normal pregnancy remain unclear. Although vascular growth contributes in early gestation, vasodilation accounts for the exponential rise seen in the last third of pregnancy. Large conductance potassium channels (BK(Ca)) are expressed in uterine vascular smooth muscle (VSM), but the extent of their role in regulating UBF in pregnancy is unclear. Therefore, we determined if BK(Ca) regulate basal UBF during ovine pregnancy. Studies were performed at 113 to 127 days and 135 to 150 days of gestation in eight pregnant ewes instrumented with uterine artery flow probes and uterine arterial and venous catheters. Tetraethylammonium chloride (TEA), a BK(Ca)-specific inhibitor at less than 1.0 mM, was infused intra-arterially into the pregnant uterine horn over 60 minutes to achieve levels of 0.001-0.35 mM while continuously monitoring UBF, arterial pressure (MAP), and heart rate (HR). Uterine arterial and venous blood was collected simultaneously to measure uterine cyclic guanosine monophosphate (cGMP) synthesis. Intra-arterial TEA dose-dependently decreased basal UBF in the early (R = 0.81, n = 36, P <.001) and late (R = 0.72, n = 31, P <.001) study periods without altering contralateral UBF, MAP, and HR. The IC(50) was 0.2 mM and basal UBF decreased >or=80% at 0.35 mM in both periods. Although UBF fell greater than 40% at estimated plasma TEA levels of 0.3 mM, uterine arterial cGMP was unchanged, uterine venous cGMP rose, and uterine cGMP synthesis was unchanged; therefore, upstream events associated with BK(Ca) activation were unaffected by blockade. These are the first data demonstrating that BK(Ca) are essential in the maintenance of basal UBF in the last third of ovine pregnancy.

Expression of phosphodiesterase 5 in maternal and fetal sheep

Ovine pregnancy is associated with elevated levels of nitric oxide. Nitric oxide stimulates cyclic guanosine monophosphate (cGMP), which results in vascular smooth muscle relaxation/vasodilation. Phosphodiesterase type 5 regulates cGMP in the urogenital track. The present study was designed to determine message expression of phosphodiesterase type 5 in the myometrium, uterine vessels, and placentome of the sheep and phosphodiesterase type 5 protein expression in the maternal and fetal placentome. Tissue was collected from 5 nonpregnant and 5 pregnant anesthetized animals (gestational day = 134 +/- 4) and frozen at -80 degrees C. Optimized reverse transcription-polymerase chain reaction was performed on all tissues, and immunohistochemistry was performed on the placentome only. Phosphodiesterase type 5 messenger ribonucleic acid levels were significantly higher in the myometrium and placentome, compared with the maternal blood vessels. Phosphodiesterase type 5 protein was immuno-localized to the vascular smooth muscle of the maternal vessels, stroma, and placental capsule only. Although phosphodiesterase type 5 messenger ribonucleic acid was present in the fetal placenta, phosphodiesterase type 5 protein was expressed only in maternally derived placental tissue. This suggests that regulation of cGMP levels and vascular tone in the umbilical circulation differs from the uterine circulation.

Development, advances and applications of diagnostic ultrasound in animals

Ultrasound has many industrial applications but it was first introduced as a medical diagnostic aid in the 1940s with its first veterinary application, the detection of ovine pregnancy, being reported in 1966. Since then, improvements in equipment quality combined with an increased awareness of the benefits of ultrasound as an imaging technique have led to its widespread use in the veterinary field. Recent advances in computer technology have significantly influenced equipment design and the miniaturisation of transducers allows intra-operative and intra-vascular applications. Software advances have improved the ability to manipulate and process data, leading to an increased amount of information being obtained from each examination and the advent of ‘remote diagnosis’. Ultrasound guided interventional techniques can now be used for diagnostic or therapeutic purposes. Many of these developments have been introduced by equipment manufacturers but have found specific applications in the veterinary field. Ultrasound is currently employed in a very diverse range of situations, not just as a diagnostic tool in the routine clinical workup of a range of species, but also for disease screening, conservation projects, commercial services, herd management and clinical research.

Cardiovascular and Renal Regulation by the Angiotensin Type 2 Receptor

The renin-angiotensin system is a coordinated hormonal cascade of major importance in cardiovascular and renal regulation. The principle effector of this system is the octapeptide angiotensin II (Ang II), which acts at 2 cell membrane receptors, AT1 and AT2. The majority of the actions of Ang II have been demonstrated to be mediated by the AT1 receptor, including growth promotion, vasoconstriction, antinatriuresis, aldosterone secretion, salt appetite, thirst, sympathetic outflow and inhibition of renin biosynthesis, and secretion.1 The AT2 receptor has been less well understood. Past studies, however, clearly demonstrated that the AT2 receptor mediates cellular differentiation and growth, opposing the actions of Ang II through the AT1 receptor.2 Studies in the mid to late 1990s demonstrated that AT2 receptor stimulation engenders an autacoid vasodilator cascade composed of bradykinin (BK), nitric oxide (NO), and guanosine cyclic 3′, 5′-monophosphate (cGMP).3–5 This discovery turned attention to the possibility that the AT2 receptor may mediate vasodilation, opposing the vasoconstrictor actions of Ang II at the AT1 receptor.6 Parallel cell signaling studies indicated that the AT2 receptor is G-protein–coupled (through Giα) and that receptor stimulation is accompanied by an increase in phosphotyrosine phosphatase activity and an inhibition of MAP kinase enzymes (p42 and p44) composing the extracellular signal-related kinase (ERK1/2). AT2 receptor-mediated inhibition of the extracellular signal-regulated kinase pathway opposed the actions of Ang II, resulting in extracellular signal-regulated kinase phosphorylation via the AT1 receptor.1,2,6,7 Work during the late 1990s through 2002 suggested that the AT2 receptor might serve as a vasodilator counterforce to the AT1 receptor.2,6,7 However, vasorelaxation was difficult to elicit in some experimental models, attributed to the relatively low level of AT2 receptor vascular expression compared with that of the …

Expression of Estrogen Receptors-α and -β in the Pregnant Ovine Uterine Artery Endothelial Cells In Vivo and In Vitro1

Estrogen is recognized to be one of the driving forces in increases in uterine blood flow through both rapid and delayed actions via binding to its receptors, ER alpha and ER beta at the uterine artery (UA) wall, and especially in UA endothelium (UAE). However, information regarding estrogen receptor (ER) expression in UAE is limited. This study was designed to test whether ERs are expressed in UAE in vivo, and if they are, whether these receptors are maintained in cultured UA endothelial cells (UAECs) in vitro. By using immunohistochemical and Western blot analyses, we clearly demonstrated ER alpha and ER beta protein expression in pregnant (Days 120-130) sheep UA and UAE in vivo and as well as cultured UAECs in vitro. Reverse transcription-polymerase chain reaction (RT-PCR) amplified both ER alpha and ER beta mRNAs in UA, UAE, and UAECs. Of interest, a truncated ER beta (ER beta2) variant due to a splicing deletion of exon 5 of the ER beta gene was detected in these cells. Quantitative RT-PCR analysis revealed that ER alpha mRNA levels are approximately 8-fold (P < 0.01) higher than that of ER beta in UAECs, indicating that ER alpha may play a more important role than ER beta in the UAEC responses to estrogen. Fluorescence immunolabeling analysis showed that ER alpha is present in both nuclei and plasma membranes in UAECs, and the latter is also colocalized with caveolin-1. The membrane and nuclear ER alpha presumably participate in rapid and delayed responses, respectively, to estrogen on UAE. Taken together, our data demonstrated that UAE is a direct target of estrogen actions and that the UAEC culture model we established is suitable for dissecting estrogen actions on UAE.

Adrenocortical responsiveness is blunted in twin relative to singleton ovine fetuses.

Twin fetuses experience much higher rates of perinatal mortality/morbidity than age- and weight-matched singletons. Across species, the prepartum increase in fetal plasma cortisol is responsible for maturing a number of systems in preparation for birth and the immediate postnatal period. In sheep, it is known that basal adrenocortical function is delayed in twins relative to singletons. Thus, it could be argued that relative immaturity in twins may explain their increased susceptibility to stress in the perinatal period and their relatively poor perinatal outcome. However, whether adrenocortical responsiveness to stress is also diminished in the twin fetus and whether the fetal cardiovascular, metabolic and endocrine defences to acute stress are comparatively weak in the twin fetus is unknown. This study investigated the effect of twinning on adrenocortical responsiveness to either the physiological stress of acute hypoxaemia or to an exogenous ACTH test, and on the fetal cardiovascular, metabolic and endocrine responses to acute hypoxaemic stress. Twenty Welsh Mountain sheep fetuses were chronically instrumented (1-2% halothane) at 121 +/- 3 days of gestation (term is ca 145 days) with amniotic and vascular catheters and with a transit-time flow probe around a femoral artery. The animals were divided into two groups based upon fetal number (singletons, n= 10; twins, n= 10), as determined at surgery. At 130 +/- 2 days, a 1 h episode of acute, isocapnic hypoxaemia (to reduce carotid P(O(2)) to 12 +/- 1 mmHg) was induced in all fetuses by reducing the maternal inspired O(2) fraction (F(IO(2)); 9% O(2) in N(2)). Fetal cardiovascular variables were recorded at 1 s intervals throughout the experimental protocol and arterial blood samples taken at appropriate intervals for biophysical (blood gases, glucose, lactate) and endocrine (catecholamines, vasopressin, cortisol, ACTH) measures. At 133 +/- 2 days a 2.5 microg bolus dose of synthetic ACTH (Synacthen; Ciba Pharmaceuticals, UK) was injected i.v. into eight of the singleton and six of the twin fetuses to determine adrenocortical steroidogenic sensitivity to exogenous ACTH. Under basal conditions, twins had lower plasma cortisol concentration, arterial blood pressure and femoral blood flow relative to singleton fetuses. Twins responded to acute hypoxaemia with similar pressor and vasopressor responses compared to singleton fetuses. However, the rate pressure product, an index of myocardial work, tended to decrease during hypoxaemia in twins, in contrast to the increase observed in singletons. Similar increases in the fetal plasma concentrations of ACTH, AVP, noradrenaline and adrenaline were observed during hypoxaemia in both groups; however, both the increments in fetal plasma concentration of cortisol in response to acute hypoxaemia and to exogenous ACTH were blunted in twins relative to singletons. This study shows that basal adrenocortical function as well as adrenocortical responsiveness is blunted in the twin relative to the singleton fetus. Further, the mechanism for adrenocortical blunting resides at the level of the adrenal cortex rather than higher up the axis. Relative adrenocortical immaturity in the twin fetus may reflect a specific endocrine adaptation to prolong gestation in multiple ovine pregnancies; however, such an adaptation does not affect the cardiovascular, metabolic or endocrine defence responses to acute hypoxaemia in the twin fetus.

A new test for early pregnancy diagnosis in sheep: determination of ovine pregnancy associated glycoprotein (OVPAG) concentration by means of a homologous radioimmunoassy

A new test for early pregnancy diagnosis in sheep: determination of ovine pregnancy associated glycoprotein (OVPAG) concentration by means of a homologous radioimmunoassy