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After birth, an alpaca cria was noticed to exhibit weakness and respiratory distress, particularly when attempting to suckle milk from the dam's udder. Clinical findings indicated the presence of bilateral choanal atresia and the animal was subsequently euthanised. A computed tomography scan and a pathological examination were performed to describe the malformation in detail. Choanal atresia is a common malformation in neonatal South American camelids, surgical treatment is not recommended. This case report provides an overview of the clinical findings as well as the results of imaging and pathologic examinations and may help to raise awareness of this malformation for early recognition., Competing Interests: Die Autoren bestätigen, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Introduction:  Tarsal malformation is a skeletal malformation of unknown aetiology associated with a variety of morphologic changes to the tarsal and metatarsal bones of the dog., Objective:  The aim of this study was to determine if early diagnosis and prevalence of tarsal malformation could be obtained at approximately 8 to 9 weeks of age in multiple litters of Bernese Mountain dogs., Methods:  A prospective study of 51 Bernese Mountain dog puppies were evaluated from 12 litters in northern Italy. Dorsoplantar radiographic views of the tarsus were obtained at 60 ± 5 days of age. Tarsal malformation was defined as an abnormal extension of the central tarsal bone on its medial side, or the presence of ectopic bone located medially to the central tarsal bone, talus and second metatarsal bones (proximomedial, distomedial and metatarsal ossification sites respectively)., Results: All puppies were found to be clinically normal. Thirty-nine of the 51 puppies showed ossification sites medial to the tarsus as defined. A metatarsal ossification was present in all dogs with either a proximo- or distomedial ossification site. No central tarsal bone extensions were observed. The remainder of the tarsometatarsal joints were normal., Clinical Significance:  Tarsal malformation can be identified in the 8- to 9-week-old Bernese Mountain dog. The clinical significance of tarsal malformation remains to be determined, either as an incidental finding or a precursor to the development of other clinically relevant and related issues in the tarsus., Competing Interests: None declared., (Thieme. All rights reserved.)

The present study aimed to investigate the impact of perinatal potassium bromate (KBrO 3 ) exposure on the development of sensorimotor reflexes and redox status, and on the histological architecture of the brain, liver, and kidney of newborn mice. Pregnant mice received 1-ml bottled drinking water daily by oral intubation and served as the control group. Another group of pregnant mice were supplemented orally with 200 mg/kg body weight KBrO 3 dissolved in drinking water from gestation day 5 to postnatal day 21. KBrO 3 induced a decrease in the postnatal body weight in the newborn mice. KBrO 3 -exposed newborn mice showed poor performance and delayed development of the sensorimotor reflexes. Histological changes, increased lipid peroxidation, and altered antioxidants were reported in the cerebrum, cerebellum, medulla oblongata, liver, and kidney of the KBrO 3 -exposed newborn mice. In conclusion, these findings demonstrated that perinatal exposure to bromate induced oxidative stress, histological and behavioral alterations, and was a potential teratogen in newborn mice.

Background: Cleft palate is a birth defect characterized by a lack of fusion between structures forming the palate. Causes include a multitude of factors, both genetic and environmental. Computed tomography (CT) is widely used to evaluate morphological features and diagnose head disorders in adult dogs. However, there is less data about its use in neonatal dogs. The purpose of this study was to perform CT evaluation of palatal defects in one-day-old puppies and to present a novel approach of 3D modeling in terms of cleft palate assessment., Results: Macroscopic and CT examinations were performed in 23 stillborn or euthanized purebred newborn puppies. On the basis of CT data, a 3D model was prepared and the cleft surface area was then calculated. A multi-stage approach, which utilised software such as 3D Slicer and Blender, was applied. Palatal defects were found in ten dogs, of which five had cleft palate, three had bilateral cleft lip and palate, one had a unilateral cleft lip and palate and one had a unilateral cleft lip. The surface area of the clefts ranged from 31 to 213 mm 2 , which made up respectfully 11 to 63% of the total surface area of the palate. No abnormalities were found in thirteen dogs and they made up the control group., Conclusions: Computed tomography and 3D modeling were very effective in evaluation of palatal disorders in newborn dogs. 3D models adapted to the natural curvature of the palate were created and more precise data was obtained. Morphological characteristics, CT findings and advanced image analysis of cleft palate in neonates obtained from these models increase the knowledge about this malformation in dogs.

It is well known that vitamin E and selenium deficiencies in domestic ruminants can lead to white muscle disease. After a clinically normal gestation period at Ouwehand Zoo in the Netherlands, a newborn giraffe ( Giraffa camelopardalis) calf showed clinical signs of white muscle disease almost immediately after birth. The calf was rejected by the mother and was euthanized 3 days later because of deterioration of clinical signs. At necropsy, pulmonary edema and pallor of skeletal and heart muscles was noted. Histologically, there was hyaline degeneration of skeletal muscle myocytes and pulmonary edema. Blood concentrations of vitamin E were ≤ 0.7 mg/L. Based on clinical, biochemical, and gross and microscopic pathological findings, congenital nutritional myodegeneration was diagnosed. This case of neonatal white muscle disease is particularly remarkable given that the diet of the dam contained more than the recommended amount of vitamin E.

Conjoined twinning is an embryological anomaly rarely reported in wild mammals and with only two previous records in Chiroptera. Here, we report a case of dicephalic parapagus conjoined twins in the Neotropical phyllostomid genus Artibeus. These twins are males and present separated heads and necks, but a conjoined trunk with an expanded upper thoracic region. They developed two complete forelimbs and two complete hindlimbs, all laterally to the trunk. There is a volume in the upper midback and between the heads that resembles a third rudimentary medial forelimb, but X-ray images only suggest the presence of medial skeletal elements of the pectoral girdle (clavicle and scapulae) in this region. The X-ray images also show that vertebral columns run separated from head until the base of lumbar region, where they form a single structure. Using ultrasound images, we detected the presence of two similarly sized and apparently separated hearts. The accumulation of study cases like this will help in the understanding of patterns and process behind this phenomena, and collection material plays a key role in this context., (© 2017 Blackwell Verlag GmbH.)

A rare complex dysraphic malformation, comprising segmental spinal dysgenesis with caudal agenesis, was found in a Holstein calf that was unable to stand and was slightly short at the lumbosacral spine with taillessness. The thoracolumbar and sacrococcygeal regions of the midline axial segments showed severe deformities. In the spinal cord, the thoracolumbar region showed severe constriction with myelodysplastic changes, and the sacrococcygeal region showed dorsoventral separation with connection to a neural mass. In the spine, vertebral anomalies according to the degree of the segmentation error were confirmed. The cervical and thoracic segments also showed milder dysraphic changes. These changes suggest a multisegmental causal insult impairing the early embryonic notochord. This represents the first bovine case definitively confirmed morphologically.

A full-term male foal born in a farm holidays in Maremma (Tuscany, Italy) was euthanized shortly after birth due to the presence of several malformations. The rostral maxilla and the nasal septum were deviated to the right (wry nose), and a severe cervico-thoracic scoliosis and anus atresia were evident. Necropsy revealed ileum atresia and agenesis of the right kidney. The brain showed an incomplete separation of the hemispheres of the rostral third of the forebrain and the olfactory bulbs and tracts were absent (olfactory aplasia). A diagnosis of semilobar holoprosencephaly (HPE) was achieved. This is the first case of semilobar HPE associated with other organ anomalies in horses., (© 2015 Blackwell Verlag GmbH.)

The objectives of the present study were to evaluate the effect of per rectal amniotic sac palpation (ASP) for pregnancy diagnosis during the late embryonic period on pregnancy loss, calving rates, and abnormalities in newborn calves. A controlled, randomized, blocked, blind experiment containing 680 lactating pregnant dairy cows with a viable embryo diagnosed by transrectal ultrasonography was performed. Two dairy operation sites (farm A and farm B) were selected. At each farm, the cows were randomly divided into control (CON) and ASP groups. The CON group was not subjected to pregnancy diagnosis via per rectum palpation. The ASP examinations were performed by one experienced veterinarian between Days 34 and 45 after breeding. All cows were reevaluated by transrectal ultrasonography only between 2 and 4 weeks later. Two calving rates were calculated: calving rate 1 (cows that calved from the initial number of pregnant cows) and calving rate 2 (cows that calved from cows pregnant at reexamination). In farm A, the percentages of early pregnancy loss were 11.5% (19 of 165) and 13.2% (24 of 182) for the CON and the ASP groups, respectively (P = 0.64). In farm B, the percentage of early pregnancy loss was 11.2% (19 of 170) for the CON group and 8.8% (14 of 159; P = 0.48) for the ASP group. In farm A, the percentage of late pregnancy loss was 7.6% (11 of 145) for the CON group and 5.5% (8 of 155; P = 0.39) for the ASP group. In farm B, the percentage of late pregnancy loss was 3.7% (5 of 137) for the CON group and 6.3% (8 of 127; P = 0.32) for the ASP group. In farm A, early pregnancy loss was higher than late pregnancy loss (12.4% vs. 6.3%; P = 0.01), and in farm B, the same tendency was detected (10.0% vs. 4.9%, for early and late pregnancy loss, respectively; P = 0.02). In farm A, calving rate 1 was 81.2% (134 of 165) for the CON group and 80.8% (147 of 182; P = 0.92) for the ASP group. Calving rate 2 for the same groups was 92.4% (134 of 145) and 94.8% (147 of 155), respectively (P = 0.68). In farm B, calving rate 1 was 77.7% (132 of 170) for the CON group and 74.8% (119 of 159; P = 0.55) for the ASP group. Calving rates 2 for the same groups were 87.4% (132 of 151) and 82.1% (119 of 145), respectively (P = 0.20). Two female calves with atresia coli were diagnosed only in the CON group. It was concluded that ASP during the late embryonic period for pregnancy diagnosis did not increase the pregnancy loss, affect calving rates, or produce abnormalities in calves., (Copyright © 2016 Elsevier Inc. All rights reserved.)

We report the first two cases of polydactyly in an atelid species: (i) a wild ca. 16-week-old infant female presenting seven digits in both feet and other bone malformations and (ii) a wild newborn male presenting six digits in both feet with the extra digit fused to the hallux., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

A 4-month-old, 20 kg, intact male, cane corso dog was presented with a slowly growing subcutaneous lesion on the left caudoventral abdominal wall. Ultrasound and computed tomography angiography revealed a subcutaneous plexus of aberrant tortuous vessels directly connected with the superficial branch of the deep circumflex iliac artery and vein. The arteriovenous malformation (AVM) was successfully surgically removed. Early recognition and surgical removal of AVM can have excellent cosmetic results and prevents potential cardiovascular complications., (© 2015 ESVD and ACVD.)

Mammals have three HP1 protein isotypes HP1 beta (CBX1), HP1 alpha (CBX3) and HP1 alpha (CBX5) that are encoded by the corresponding genes Cbx1, Cbx3 and Cbx5. Recent work has shown that reduction of CBX3 protein in homozygotes for a hypomorphic allele (Cbx3hypo) causes a severe postnatal mortality with around 99 percent of the homozygotes dying before weaning. It is not known what the causes of the postnatal mortality are. Here we show that Cbx3hypo/hypo conceptuses are significantly reduced in size and the placentas exhibit a haplo-insufficiency. Late gestation Cbx3hypo/hypo placentas have reduced mRNA transcripts for genes involved in growth regulation, amino acid and glucose transport. Blood vessels within the Cbx3hypo/hypo placental labyrinth are narrower than wild-type. Newborn Cbx3hypo/hypo pups are hypoglycemic, the livers are depleted of glycogen reserves and there is almost complete loss of stored lipid in brown adipose tissue (BAT). There is a 10-fold reduction in expression of the BAT-specific Ucp1 gene, whose product is responsible for nonshivering themogenesis. We suggest that it is the small size of the Cbx3hypo/hypo neonates, a likely consequence of placental growth and transport defects, combined with a possible inability to thermoregulate that causes the severe postnatal mortality.

Musculoskeletal system deformities were observed in 24 (34.3%) of 70 neonatal dairy calves that presented with different congenital abnormalities. Among them, 19 calves (27.1%), the majority of which were crossbred Jersey calves of either gender with mean (± s.e.) body weight 22.00 kg ± 1.17 kg and aged 7.11 ± 1.16 days, were presented for treatment of congenital knuckling. Five of the knuckling calves had additional concurrent congenital conditions and were excluded from the present study. All of the remaining 14 calves showing moderate, bilateral fetlock knuckling had a wooden or polyvinyl chloride (PVC) splint applied to the palmar or plantar aspect of the affected limbs. All of the animals received a dose of the analgesic tolfenamic acid intramuscularly, and were randomly allocated to two equal groups. Calves of Group I additionally received oxytetracycline (20 mg/kg intravenous daily for 3 days). The condition resolved satisfactorily in 83.3% and 80.0% calves from the two groups, respectively. The left and right fetlock angle (mean ± SE) reduced significantly (p ≤ 0.01) from 50.57° ± 4.20° to 4.00° ± 2.27° and 48.71° ± 2.37° to 5.33° ± 3.03°, respectively in animals of Group I. In Group II calves, the angles showed reduction from 50.86° ± 2.94° to 4.20° ± 2.75° and from 48.71° ± 3.14° to 6.80° ± 3.34°, respectively. From the present study, it was concluded that bilateral moderate fetlock knuckling in the neonatal dairy calves can be managed satisfactorily with early application of splints. Supplementary use of oxytetracycline at repeated doses of low toxicity had only a marginally beneficial effect.

Background: p38 MAPK activity plays an important role in several steps of the osteoblast lineage progression through activation of osteoblast-specific transcription factors and it is also essential for the acquisition of the osteoblast phenotype in early development. Although reports indicate p38 signalling plays a role in early skeletal development, its specific contributions to adult bone remodelling are still to be clarified., Methodology/principal Findings: We evaluated osteoblast-specific deletion of p38α to determine its significance in early skeletogenesis, as well as for bone homeostasis in adult skeleton. Early p38α deletion resulted in defective intramembranous and endochondral ossification in both calvaria and long bones. Mutant mice showed reduction of trabecular bone volume in distal femurs, associated with low trabecular thickness. In addition, knockout mice also displayed decreased femoral cortical bone volume and thickness. Deletion of p38α did not affect osteoclast function. Yet it impaired osteoblastogenesis and osteoblast maturation and activity through decreased expression of osteoblast-specific transcription factors and their targets. Furthermore, the inducible Cre system allowed us to control the onset of p38α disruption after birth by removal of doxycycline. Deletion of p38α at three or eight weeks postnatally led to significantly lower trabecular and cortical bone volume after 6 or 12 months., Conclusions: Our data demonstrates that, in addition to early skeletogenesis, p38α is essential for osteoblasts to maintain their function in mineralized adult bone, as bone anabolism should be sustained throughout life. Moreover, our data also emphasizes that clinical development of p38 inhibitors should take into account their potential bone effects.

A 24-hour-old Holstein bull calf with notomelia was donated to the Atlantic Veterinary College. The extra limb was on the right side of the caudal neck adjacent to the withers. The limb was surgically removed under general anesthesia. The calf was adopted and discharged with no complications.

Dipeptidyl Peptidase (DPP) 4 and related dipeptidyl peptidases are emerging as current and potential therapeutic targets. DPP9 is an intracellular protease that is regulated by redox status and by SUMO1. DPP9 can influence antigen processing, epidermal growth factor (EGF)-mediated signaling and tumor biology. We made the first gene knock-in (gki) mouse with a serine to alanine point mutation at the DPP9 active site (S729A). Weaned heterozygote DPP9 (wt/S729A) pups from 110 intercrosses were indistinguishable from wild-type littermates. No homozygote DPP9 (S729A/S729A) weaned mice were detected. DPP9 (S729A/S729A) homozygote embryos, which were morphologically indistinguishable from their wild-type littermate embryos at embryonic day (ED) 12.5 to ED 17.5, were born live but these neonates died within 8 to 24 hours of birth. All neonates suckled and contained milk spots and were of similar body weight. No gender differences were seen. No histological or DPP9 immunostaining pattern differences were seen between genotypes in embryos and neonates. Mouse embryonic fibroblasts (MEFs) from DPP9 (S729A/S729A) ED13.5 embryos and neonate DPP9 (S729A/S729A) mouse livers collected within 6 hours after birth had levels of DPP9 protein and DPP9-related proteases that were similar to wild-type but had less DPP9/DPP8-derived activity. These data confirmed the absence of DPP9 enzymatic activity due to the presence of the serine to alanine mutation and no compensation from related proteases. These novel findings suggest that DPP9 enzymatic activity is essential for early neonatal survival in mice.

Malformations can occur in all living species, but there is little information about anomalies that occur in snakes and their frequency. This study assessed malformations in newborn South American pit vipers (Bothrops jararaca) and South American rattlesnakes (Crotalus durissus) from wild captured pregnant females (240 and 35 litters, respectively). Newborn snakes were measured, weighed, sexed and studied grossly and by radiography for the presence of malformations. Ninety-five malformed pit vipers were identified from 4,087 births (2.3%), while 36 malformed rattlesnakes were found from 324 births (11.1%). Spinal abnormalities were the most common in both species, followed by fusion of ventral scales. Pit vipers showed a greater range of malformations including schistosomia (22.1%), kinked tail (13.7%), bicephaly (3.1%) and hydrocephaly (2.1%)., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: The neonatal period is associated with high morbidity and mortality in cloned calves., Objective: To describe morbidity and mortality in cloned calves from birth to 2 years of age., Animals: Thirty-one somatic cell-derived Holstein calves delivered at a veterinary teaching hospital., Methods: Medical files were retrospectively analyzed., Results: Four calves were stillborn. Five calves born alive had physical congenital defects. Twenty-three calves had an enlarged umbilical cord. Laboratory abnormalities included acidemia, respiratory acidosis, hyperlactatemia, anemia, stress leukogram, decreased total protein, albumin and globulins, and increased creatinine. Twenty-five calves survived the 1st hour of life. Among them, 11 stood without assistance within 6 hours of birth, 10 calves took longer than 6 hours to stand, and 4 never stood. Twenty-two calves suffered from anorexia. Twelve calves had complications arising from umbilical cord infections. Three calves developed idiopathic hyperthermia (>40°C). Eight calves suffered from gastrointestinal problems, including ruminal distension, abomasal ulcers, neonatal enteritis, intussusception, and abomasal displacement. Mortality between birth and 3 weeks of age was 32% (10/31). Causes of death and reasons for euthanasia included stillbirths, respiratory failure, and limb deformities. Mortality between 3 weeks and 2 years of age was 19% (4/21), with deaths in this group attributed to generalized peritonitis and complications arising from umbilical infections. Overall, mortality rate within 2 years of age was 14/31 (45%)., Conclusion and Clinical Importance: Respiratory problems, limb deformities, and umbilical infections were the most common causes of morbidity and mortality in these cloned calves., (Copyright © 2013 by the American College of Veterinary Internal Medicine.)

This is the first German case report of an alpaca cria suffering from a congenital vulvahypoplasia. Symptoms, diagnostics and therapy are described. The 24-hours-old cria was referred to the hospital due to reduced general condition and colic. The existent vulvahypoplasia led to impaired urination, causing further complications such as urovagina and urinary stasis up to the renal pelvis. Surgical construction of the rima vulvae cured the cria. As indicated by several cases published on the clinical picture of vulvahypoplasia during recent years, this congenital deformation could become an increasing problem in the alpaca population.

The aims of this study was to evaluate the effects of oil-resin of Copaiba (Copaifera duckei Dwyer), aired in vaginal cream on the reproductive performance of female rats (Rattus norvegicus). To determine the components of the C. duckei oleoresin, gas chromatography coupled with mass spectrometry (CG-MS) was used, and considering the trans-caryophyllene sesquiterpene as a phytochemical marker in the oleoresin. Due to the extensive use of copaiba oleoresin in the suppository form for gynecological infections, an evaluation was carried out on the effects of copaiba oleoresin (Copaifera duckei Dwyer), delivered in a vaginal cream, on the reproductive performance of female Wistar rats. For this purpose, three groups (n=5-6/group) of female rats were treated as follows: 1--vaginal cream of copaiba oleoresin (28.6 mg/kg), 2--base vaginal cream and 3--control (physiological saline 0.9%), administered intravaginally, for 30 days before pregnancy, and from day zero to day 20 during pregnancy. Laparotomy was performed on the 21st day of pregnancy, followed by the determination of reproductive variables: number of live and dead fetuses, mass of the fetuses and placentas, number of implantations and resorptions, number of corpora lutea, pre- and post-implantation loss, and analyses of the fetuses with regard to external and internal anomalies and/or malformations (skeletal and visceral). The trans-caryophyllene present in the sample is suggested as a phytochemical marker and the results of this study demonstrate an absence of maternal toxicity and foetotoxicity embryofoetotoxicity at the dose administered, corresponding to ten times the recommended dose for use in humans. Accordingly, no significant statistical difference was observed between the treated and control groups, for the variables analyzed. Thus, it is concluded that the vaginal cream containing 2.5% copaiba oleoresin is safe during gestation, in female rats (Rattus norvegicus) of the Wistar strain., (Copyright © 2011 Elsevier GmbH. All rights reserved.)

Objectives: Characterise a lethal genetic disorder in Poll Merino/Merino sheep, Design: Pathological description of a new congenital multisystem disorder in a commercial sheep flock, and analysis of breeding data collected each lambing season between 2004 and mid-lambing season 2010., Procedure: Necropsies were conducted on six affected lambs and the mode of inheritance of the disorder was determined by pedigree and segregation analyses., Results: The affected lambs were dwarfs with multiple defects in several organs, including skeleton, heart, liver and kidneys. The disorder has been named brachygnathia, cardiomegaly and renal hypoplasia syndrome (BCRHS). Segregation analysis suggests the disorder is transmitted as an autosomal trait with a recessive mode of inheritance. An annual incidence of the disorder in the discovery flock of up to 2.5% was recorded., Conclusions: As a lethal disorder, the occurrence of BCRHS raises potential ethical and economic concerns for Merino breeders. The development of a DNA test would be useful to investigate its distribution in the Australian wool-sheep population. As the disorder affects both the skeleton and several critical organs, including the heart, it may provide a potential animal model for investigating key developmental processes in humans and other animals., (© 2011 The Authors. Australian Veterinary Journal © 2011 Australian Veterinary Association.)

Ethical and moral issues rule out the use of human induced pluripotent stem cells (iPSCs) in chimera studies that would determine the full extent of their reprogrammed state, instead relying on less rigorous assays such as teratoma formation and differentiated cell types. To date, only mouse iPSC lines are known to be truly pluripotent. However, initial mouse iPSC lines failed to form chimeric offspring, but did generate teratomas and differentiated embryoid bodies, and thus these specific iPSC lines were not completely reprogrammed or truly pluripotent. Therefore, there is a need to address whether the reprogramming factors and process used eventually to generate chimeric mice are universal and sufficient to generate reprogrammed iPSC that contribute to chimeric offspring in additional species. Here we show that porcine mesenchymal stem cells transduced with 6 human reprogramming factors (POU5F1, SOX2, NANOG, KLF4, LIN28, and C-MYC) injected into preimplantation-stage embryos contributed to multiple tissue types spanning all 3 germ layers in 8 of 10 fetuses. The chimerism rate was high, 85.3% or 29 of 34 live offspring were chimeras based on skin and tail biopsies harvested from 2- to 5-day-old pigs. The creation of pluripotent porcine iPSCs capable of generating chimeric offspring introduces numerous opportunities to study the facets significantly affecting cell therapies, genetic engineering, and other aspects of stem cell and developmental biology.

A 10-day-old female alpaca (Vicugna pacos) cria with a history of urinary straining and dribbling was presented for evaluation. The animal had markedly elevated blood fibrinogen (800 mg/dl), mildly elevated phosphorus (9.3 mg/dl), and minimally elevated blood urea nitrogen (38 mg/dl) concentrations. The total protein (5.0 g/dl) concentration was mildly decreased. These findings were suggestive of mild renal disease. An abdominal ultrasound revealed bilateral hydronephrosis and hydroureter, and no urinary bladder was identified. Gross postmortem examination revealed urinary bladder agenesis and bilateral hydronephrosis and hydroureter, with both ureters opening into a sinus in the caudal vagina. Histologic examination of the kidneys showed necrosuppurative pyelonephritis with pelvic dilation, and both ureters had mild lymphoplasmacytic and histiocytic inflammation.

We kept 48 gravid short-tailed pit vipers (Gloydius brevicaudus) under four laboratory thermal conditions during gestation and collected 10 females from the field soon before they gave birth to test whether Shine's (1995) maternal manipulation hypothesis applies to temperate reptiles. Females thermoregulated more precisely but did not shift their selected body temperatures during pregnancy, with females at high body temperatures giving birth early in the breeding season. The lowest (22 degrees C) and highest (32 degrees C) temperature treatments Increased maternal mortality and resulted in production of offspring with smaller body dimensions. More deformed offspring were produced at 32 degrees C, and more poorly performing offspring were produced at 22 degrees C. In the field, air temperatures lower than 22 degrees C and higher than 32 degrees C accounted for about 9% and 33% of total temperature readings, respectively. However, offspring produced by field-caught females did not differ from those produced by laboratory-kept females with body temperatures optimal for embryonic development in nearly all traits examined. This suggests that in nature, gravid females avoid exposure of their embryos to temperature extremes through thermoregulation. Our study validates the key prediction of the maternal manipulation hypothesis that maternal thermoregulation should enhance fitness-related offspring traits, and demonstrates that viviparity evolves in temperate reptiles because internal development shields offspring from temperature extremes.

The features of a calf with a split cord malformation are described. Clinically, there was severe cervicothoracic kyphoscoliosis and an interscapular dermal sinus associated with cerebrospinal fluid drainage. Using magnetic resonance imaging, complete duplication of the spinal cord at the cervical intumescence was detected. There was associated syringohydromyelia, multiple cervicothoracic vertebral malformations resulting in kyphoscoliosis and rachischisis, herniation of the cerebellar vermis, meningoencephalocele, and calvarial defects.

A 5-day-old Simmental calf was referred to our department for atresia ani and postural abnormalities caused by skeletal deformities. The calf had a short and deviated tail and a bowed hind limb. The calf appeared like a male because of the prepuce and penis located just near the teats and the absence of female external genitalia. During the necropsy, a horseshoe kidney, single ureter that originated from the kidney, and bilateral uterine horns with one ovary each were detected. The ureter, blind-ended large intestine, and bilateral uterine horns were connected to a dilated cloaca having two sacs, which were filled with a yellowish brown viscous fluid admixed with meconium and urine. Skeletal deformities found included scoliosis, partial synostosis of vertebrae, deviation of rudimentary sacrum and coccygeal vertebrae, and narrowed pelvic cavity. This is the first report of an anomalous combination including urogenital, large intestinal, and skeletal deformities in cattle.

Congenitally hypomyelinated shiverer mice fail to generate compact myelin and die by 18-21 weeks of age. Using multifocal anterior and posterior fossa delivery of sorted fetal human glial progenitor cells into neonatal shiverer x rag2(-/-) mice, we achieved whole neuraxis myelination of the engrafted hosts, which in a significant fraction of cases rescued this otherwise lethal phenotype. The transplanted mice exhibited greatly prolonged survival with progressive resolution of their neurological deficits. Substantial myelination in multiple regions was accompanied by the acquisition of normal nodes of Ranvier and transcallosal conduction velocities, ultrastructurally normal and complete myelination of most axons, and a restoration of a substantially normal neurological phenotype. Notably, the resultant mice were cerebral chimeras, with murine gray matter but a predominantly human white matter glial composition. These data demonstrate that the neonatal transplantation of human glial progenitor cells can effectively treat disorders of congenital and perinatal hypomyelination.

Purpose: The purpose of this study was to reassess the role of the lens as an "embryonic organizer" of ocular tissues., Methods: We ablated the lens in mice by lens-specific expression of an attenuated version of diphtheria toxin A subunit(Tox176) driven by a modified crystallin promoter. Alterations in the differentiation programs of ocular tissues were examined by hematoxylin and eosin staining, in situ hybridization, and immunohistochemistry., Results: Transgenic mice in the family OVE1757 exhibited severe microphakia. Apoptotic lens fibers were seen by embryonic day 15 (E15) and the lenses were completely ablated by post natal day 8. Multiple defects were seen in the anterior chamber. Corneal endothelial cells did not differentiate properly. The mesenchymal cells that would normally give rise to the endothelial layer were found to express N-cadherin, but they failed to form tight junctions and undergo a mesenchymal-to-epithelial transition. Although early specification of the presumptive ciliary body and iris was detected, subsequent differentiation of the iris was blocked. No dramatic changes were seen in the development of the retina., Conclusions: These results support the hypothesis that an intact lens is essential for proper differentiation of both the corneal endothelium and the iris and that the lens "organizes" the development of tissues in the anterior chamber.

Prader-Willi syndrome (PWS) is an imprinted genetic obesity disorder characterized by abnormalities of growth and metabolism. Multiple mouse models with deficiency of one or more PWS candidate genes have partially correlated individual genes with aspects of the PWS phenotype, although the genetic origin of defects in growth and metabolism has not been elucidated. Gene-targeted mutation of the PWS candidate gene Magel2 in mice causes altered circadian rhythm output and reduced motor activity. We now report that Magel2-null mice exhibit neonatal growth retardation, excessive weight gain after weaning, and increased adiposity with altered metabolism in adulthood, recapitulating fundamental aspects of the PWS phenotype. Magel2-null mice provide an important opportunity to examine the physiological basis for PWS neonatal failure to thrive and post-weaning weight gain and for the relationships among circadian rhythm, feeding behavior, and metabolism.

During late may 2004, Some dairy cows at Al-Kharj area of central Saudi Arabia, gave birth to severely malformed calves which died, few hours to few days following birth. Samples were collected from the affected calves and their dams of virological and serological investigations. Bovine viral diarrhoea virus was detected by capture enzyme linked immuno-sorbent assay (ELISA) in the brains of affected calves. Serum antibodies were detected in the dams. The present study indicated that in spite of vaccination against BVD in the country, still severe affections of the disease are encountered. Further insight epidemiological studies to elucidate the BVD situation in Saudi Arabia is urgently needed.

In mammals, abnormal increases in fetal androgens disrupt normal development of the female phenotype. Due to the recent concern regarding environmental androgen-active chemicals, there is a need to identify sources of fetal androgen variation and sensitive developmental markers for androgenic activity in female rats. Anogenital distances (AGD), nipple retention, reproductive tract, and external genitalia are morphological parameters organized by prenatal androgens and are predictive of altered masculinized/defeminized phenotype in adult female mice and rats. The objectives of this study were to (1) characterize the natural prenatal androgen environment of rats including the magnitude of the intrauterine position (IUP) effect, (2) characterize the permanent effects of prenatal androgen exposure on female rats, and (3) determine the ability of AGD and areolas to predict these permanent androgenic alterations in female rats. Untreated male fetal rats had higher tissue testosterone (T) concentrations than females in the amniotic fluid, reproductive tract, gonad, and fetal body. The intrauterine position (IUP) of male and female fetuses did not affect T concentrations or AGD in male or female rats at gestational day (GD) 22. Female offspring exposed to 0, 1.5, and 2.5 mg/kg/day testosterone propionate (TP) on GDs 14-18 displayed increased AGD at postnatal day (PND) 2 and decreased nipples at PND 13 and as adults. TP-induced changes in neonatal AGD and infant areola number were reliable indicators of permanently altered adult phenotype in female rats. Further, females in the two high-dose groups displayed increased incidences of external genital malformations and the presence of prostatic tissue, not normally found in female rats.

Although a majority of clones are born normal and apparently healthy, mortality rates of nearly 30% are described in many reports. Such losses are a major limitation of cloning technology and represent substantial economic investment as well as justifiable animal health and welfare concerns. Prospective, controlled studies are needed to understand fully the causes of neonatal mortality in clones and to develop preventive and therapeutic strategies to minimize losses. We report here the findings of studies on the hematologic and biochemical profiles of cloned and control calves in the immediate 48-h postpartum period. Cloned calves were similar to control calves for a majority of parameters studied including blood gases, concentrations of plasma proteins, minerals and electrolytes, and white blood cell, neutrophil, lymphocyte, and platelet counts. The most notable differences between clones and controls in this study were reduced red- and white-blood cell counts in clones at birth and 1 h of age. As a group, plasma electrolyte concentrations were more variable in clones, and the variability tended to be shifted either higher (sodium, chloride) or lower (potassium, bicarbonate) than in controls. Previously, we noted differences in carbohydrate parameters, the length of time required for clones to make the neonatal adaptation to life ex utero, and morphology of the cloned placenta. Taken together, our findings suggest that cloned calves experience greater difficulty adjusting to life ex utero and that further research is warranted to determine the nature of the relationship between the physiological differences noted here in clones at birth and concomitant abnormal placental morphology.

The period immediately after birth is a vital time for all newborn calves as the cardiovascular, respiratory, and other organ systems adapt to life ex utero. Reported neonatal mortality rates suggest this period to be especially critical in cloned calves; yet prospective, controlled studies on the physiological status of these calves are lacking. The objectives of this study were to compare neonatal (birth to 48 h of age) physical and clinical characteristics and placental morphology of cloned and embryo transfer control calves delivered by cesarean section after induced labor. All calves were raised under specialized neonatal-care protocols at a large-animal veterinary research and teaching hospital. Cloned calves were similar to controls for many parameters studied. Notable exceptions included developmental delays of important physical adjustment parameters and enlargement of the umbilical region. Placentas associated with cloned calves contained fewer total placentomes, a twofold increase in surface area and mass per placentome, and a shift in placentome morphology toward larger, flatter placentomes. The most striking clinical variations detected in clones were hypoglycemia and hyperfructosemia, both measures of carbohydrate metabolism. Because the placenta is known to be the source of plasma fructose in newborn calves, increased fructose production by the cloned placenta may be an important factor in the etiology of umbilical and cardiac anomalies in clones observed in this and other studies.

The John Heinz National Wildlife Refuge is subject to pollution from multiple sources. We studied development of snapping turtle (Chelydra serpentina) and painted turtle (Chrysemys picta) embryos from the refuge from 2000 through 2003. Mean annual deformity rate of pooled painted turtle clutches over four years ranged from 45 to 71%, while that of snapping turtle clutches ranged from 13 to 19%. Lethal deformities were more common than minor or moderate deformities in embryos of both species. Adult painted turtles had a higher deformity rate than adult snapping turtles. Snapping turtles at JHNWR had high levels of PAH contamination in their fat. This suggests that PAHs are involved in the high level of deformities. Other contaminants may also play a role. Although the refuge offers many advantages to resident turtle populations, pollution appears to place a developmental burden on the life history of these turtles.

Polycyclic aromatic hydrocarbons (PAHs) are toxic compounds found in the John Heinz National Wildlife Refuge in Philadelphia, Pennsylvania. We assessed the impact of PAHs and crude oil on snapping turtle development and behavior by exposing snapping turtle eggs from the Refuge and from three clean reference sites to individual PAHs or a crude oil mixture at stage 9 of embryonic development. Exposure to PAHs had a significant effect on survival rates in embryos from one clean reference site, but not in embryos from the other sites. There was a positive linear relationship between level of exposure to PAHs and severity of deformities in embryos collected from two of the clean reference sites. Neither righting response nor upper temperature tolerance (critical thermal maximum, CTM) of snapping turtle hatchlings with no or minor deformities was significantly affected by exposure to PAHs.

Case Description: 6 female alpacas, ranging in age from < 1 day to > 2 years, were examined because of primary owner complaints related to urogenital malformation., Clinical Findings: In all instances, the vulva was totally to subtotally imperforate. One neonate had failure of passive transfer of immunity and mild azotemia at the time of initial examination. No additional urogenital malformations were detected in any of the alpacas., Treatment and Outcome: Vulvoplasty performed via local anesthesia was successful in all alpacas. The neonate with failure of passive transfer received a plasma transfusion. Postsurgical wound management was limited to topically applied medications., Clinical Relevance: Congenital vulvar deformity in alpacas may result in interference with urine outflow. Neonates with a completely imperforate vulva may be brought to veterinarians for examination on an emergency basis. Less severely affected alpacas may be examined later in life with owner complaints ranging from stranguria or dysuria to urogenital malformation. No other primary abnormalities of the urogenital tract in alpacas have been reported, to the authors' knowledge. Vulvoplasty, performed with local anesthesia, resolves obstructed urine flow. Because it is possible that this condition is heritable, affected alpacas, and possibly their sires and dams, should not be used for breeding.

The membrane serine protease matriptase is required for epidermal barrier function, hair formation, and thymocyte development in mice, and dysregulated matriptase expression causes epidermal squamous cell carcinoma. To elucidate the specific functions of matriptase in normal and aberrant epidermal differentiation, we used enzymatic gene trapping combined with immunohistochemical, ultrastructural, and barrier function assays to delineate the spatio-temporal expression and function of matriptase in mouse keratinized tissue development, homeostasis, and malignant transformation. In the interfollicular epidermis, matriptase expression was restricted to postmitotic transitional layer keratinocytes undergoing terminal differentiation. Matriptase was also expressed in keratinizing oral epithelium, where it was required for oral barrier function, and in thymic epithelium. In all three tissues, matriptase colocalized with profilaggrin. In staged embryos, the onset of epidermal matriptase expression coincided with that of profilaggrin expression and acquisition of the epidermal barrier. In marked contrast to stratifying keritinized epithelium, matripase expression commenced already in undifferentiated and rapidly proliferating profilaggrin-negative matrix cells and displayed hair growth cycle-dependent expression. Exposure of the epidermis to carcinogens led to the gradual appearance of matriptase in a keratin-5-positive proliferative cell compartment during malignant progression. Combined with previous studies, these data suggest that matriptase has diverging functions in the genesis of stratified keratinized epithelium, hair follicles, and squamous cell carcinoma.

Congenital heart disease (CHD) is defined as a morphologic defect of the heart or associated great vessels present at birth. Abnormalities are caused by alterations or arrests in particular phases of embryonic development of the fetal heart. The term congenital does not imply that the defect was inherited, and the defect may have occurred spontaneously or secondary to a drug or toxin. By studying families of animals with specific CHDs, many defects have also been shown to be heritable.Additionally, if the defect was caused by a spontaneous de novo mutation,that individual has the potential to transmit the mutation to offspring. The diagnosis of CHD is important not only to the health of the patient but to eliminate affected individuals from the breeding pool.

We describe the echocardiographic findings in a 4-day-old thoroughbred foal with an aortico-pulmonary septal defect. The foal had labored breathing, cyanotic mucous membranes and a continuous grade 5/6 heart murmur with point of maximal intensity over the base of the heart on the right side. Echocardiographically, there was a large communication between the aorta and the pulmonary artery just dorsal to the base of the heart. The cardiac anomaly seen during the echocardiographic exam was confirmed at necropsy where a large communication between the two great vessels was observed. These findings correlate with previous studies in humans, dogs, and cats. The possible failure in the embryologic development that led to this unusual cardiac anomaly is discussed.

The ultrastructure of neurons, astrocytes, and capillaries in the sensorimotor cortex of three-month-old offspring of alcoholic male rats (8 g/kg of 50% alcohol solution daily for four weeks) was studied. Apart from signs of delayed maturation of nerve and glial cell processes, some cortical areas showed destructive changes affecting a proportion of neurons along with elements of compensatory-adaptive processes in some nerve cells. Membrane and myelin-like intranuclear inclusions and changes in the Golgi complex were characteristic features of the damage to populations of cortical neurons. Swelling of astrocytes, deformation of capillaries and changes in their ultrastructure, with accumulation of atypical inclusions in pericapillary astrocyte processes, degraded reciprocal exchange processes between blood and neurons. The possible role of the ischemic-hypoxic factor in delayed changes in the ultrastructure of the sensorimotor cortex in the offspring of alcoholic males is discussed.

Schistosomus reflexus (SR) is a rare and fatal congenital disorder. Primarily observed in ruminants, its defining features include spinal inversion, exposure of the abdominal viscera because of a fissure of the ventral abdominal wall, limb ankylosis, positioning of the limbs adjacent to the skull and, lung and diaphragm hypoplasia. Variable components of SR include scoliosis, cleft sternum, exposure of thoracic viscera, and abnormalities of the digestive and urogenital systems. This report presents the findings from an anatomical analysis of a female Holstein SR calf with thoracoschisis, scoliosis and anomalies of the appendicular skeleton, cardiovascular, respiratory, digestive and urogenital systems. Many of these malformations have not been previously reported. The reproductive tract of this case is particularly unique, displaying Muellerian duct abnormalities. These abnormalities suggest SR occurs as early as the post-gastrulation embryo and involves the intermediate mesoderm. Preliminary analysis of associated cases suggests that SR has a genetic aetiology.

In a retrospective study on 265 cases of sporadic bovine abortions, stillbirths, and neonatal deaths in Atlantic Canada (1990 to 2001), an etiological diagnosis was made in 117 cases (44.2%). The cases were divided into 2 groups: 234 abortions, and 31 stillbirths and neonatal deaths. Identified causes of abortion were bacteria (24.4%), fungi (6.8%), viruses (6.0%), protozoa (Neospora spp.) (2.1%), congenital anomalies (0.4%), and miscellaneous conditions (1.3%). In addition, placentitis without demonstrable infectious agents was observed in 17 (7.3%). Of the 31 cases of stillbirth and neonatal death, identified causes were dystocia (22.5%), congenital anomalies (22.5%), meconium aspiration syndrome (16.1%), and miscellaneous conditions (6.5%). No etiological diagnosis was made in 59% of abortions and 32.4% of stillbirths and neonatal deaths. The 3 most common identifiable causes of abortion in this study were bacterial, fungal, and viral infections.

A wave of abortions, stillbirths and deformities in sheep occurred at the Al-Ahsa oasis in the eastern region of Saudi Arabia in the second half of 1999. The abortions were recorded in August and September and stillbirths and deformities in neonates were observed in October. Adult sheep were clinically normal. A virus was isolated in chicken embryos, adapted to Vero cell culture and further identified as bluetongue (BT) virus. The virus isolated was not neutralised by the Akabane virus. Reference hyperimmune serum against antibodies to BT virus detected in the sera of the dams gave positive results for BT but negative results for both Akabane and bovine viral diarrhoea virus. It was concluded that the outbreak was caused by a virus of the BT serogroup. The authors present the clinico-pathological and epidemiological situation of the disease outbreak.

Thyroid hyperplasia and musculoskeletal deformity, described in foals in western Canada, has not been recognized as a common cause of neonatal foal mortality in Ontario. A case is reported from Ontario, with clinical and histopathological findings consistent with the syndrome described in western Canada.