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Genomic insights into the population history of fat-tailed sheep and identification of two mutations that contribute to fat tail adipogenesis.

INTRODUCTION: Since their domestication, domestic sheep (Ovis aries) have been culturally and economically significant farming animals worldwide. Fat-tailed sheep serve as a unique genetic resource for understanding adipogenesis and adaptive evolution in livestock. OBJECTIVES: Several genomic analyses have been conducted on various sheep breeds to elucidate the genome and regulation mechanism of the fat tail trait, prior genomic studies have failed to reconcile conflicting evidence about the genetic basis of tail morphology, particularly regarding the roles of PDGFD and BMP2. METHODS: Here, we conducted whole-genome resequencing of 283 sheep, encompassing 66 domestic breeds and 5 wild ovine species, to investigate the domestication history and selection signatures of fat-tailed sheep. Additionally, we performed transcriptome sequencing on adipose tissue to identify differentially expressed genes and cellular assays to validate these results. RESULTS: Demographic analysis revealed that domestic sheep descended from Asiatic mouflon and fat-tailed sheep began to diverge from thin-tailed sheep approximately 4.4-7.5 thousand years ago in East Asia. Chinese indigenous sheep were classified into Mongolian, Kazakh, Tibetan, and Yunnan populations. The Yunnan population may have experienced more recent genetic introgression from wild species, rather than an independent domestication event. Moreover, many potential regions associated with the fat-tailed phenotype (DDI1, PDGFD, and BMP2) were identified by selective sweep and genome-wide association analyses. Additionally, a fine-scale analysis of fat-tailed and thin-tailed sheep revealed two novel mutations: a G/A missense variant of PDGFD (Chr15: 3900312) and a C/T missense variant of BMP2 (Chr13: 48462350), both of which were significantly associated with tail adiposity. Functional validation demonstrated that mutant A-PDGFD significantly activated PFGFD expression and reduced fat deposition compared to wildtype. The C-BMP2 mutant activated BMP2 expression and promoted preadipocyte fat deposition. CONCLUSION: Our study provides the first evidence that these genes jointly regulate fat tail development through complementary mechanisms: PDGFD promotes adipose expansion, whereas BMP2 modulates energy partitioning. These findings offer new insights into the evolutionary history of fat-tailed sheep and identify potential targets for precision breeding in small ruminants.

Animals

Purification, properties and kinetics of sheep and human renin substrates.

Sheep plasma renin substrate was purified 1,200-fold by using nephrectomised sheep plasma, followed by DEAE-Sephadex chromatography and gel filtration. The purified substrate contained 8 mu-g angiotensin II/mg protein and had an estimated molecular weight of 52,000. The kinetic characteristics of the purified substrate were identical both to those of unpurified nephrectomised sheep plasma and to normal sheep plasma substrates. At pH 7.5, K-m of the human renin-sheep substrate reaction was 0.29 mu-M and for sheep renin-sheep substrate, 2.0 mu-M. Sheep substrate was susceptible to peptic digestion with generation of pepsitensin. Human renin substrate was less readily purified. DEAE-Sephadex chromatography of plasma from pregnant women at 36-40 weeks' gestation produced a 70-fold increase in purity (0.9 mu-g angiotensin II/mg protein). No further increase was achieved with gel filtration. Human renin substrate behaved as a larger (mol. wt. 82,000) more anionic protein than sheep substrate and was resistant to the proteolytic actions of both pepsin and sheep renin. K-m for the human renin-human substrate reaction was high and could not be accurately determined (range 3-8 mu-M, mean 5.7 mu-M). The presence of human substrate in a human renin-sheep substrate system did not alter the measured initial velocity. In both sheep and man, the normal concentration of renin substrate is considerably less than K-m and must therefore be considered a determinant of angiotensin production rate in vivo.

Angiotensin II

Reversal by testosterone of atrophy of accessory genital glands of castrated male sheep. A histologic and morphometric study.

The histologic features of male accessory genital glands of entire sheep (group I), castrated sheep (group II), castrated sheep treated with 40 daily intramuscular injections of 50 milligrams testosterone propionate (group III), and castrated sheep treated with 600 milligrams testosterone propionate 72 hours before death (group IV) were compared. Sheep were castrated at 3 months old and all sheep were killed when 15 months old. Volume fractions of glandular tissue, intralobular fibromuscular tissue and perilobular fibromuscular tissue of the seminal vesicles and Cowper's glands fluctuated significantly (P less than 0.05) during postcastration atrophy and after repeated testosterone treatment. Atrophy in sheep in group II was least in the prostate but greatest in Cowper's glands, seminal vesicles and ampullae of vasa deferentia. Seminal vesicle plexi, whose cytons had a statistically significant (P less than 0.05) degree of shrinkage, also were atrophied. After treatment with testosterone the postcastration atrophy of plexal neurons was almost reversed in sheep in group III. There also was hypertrophy of epithelial cells but the testosterone treatment failed to reduce to normal the fibromuscular volume fraction of the accessory genital glands. Testosterone propionate treatment of sheep in group IV failed to elicit appreciable morphologic changes. These results are compared with our previous findings on the content and uptake of zinc by the accessory genital glands. It is suggested that accumulation of zinc in the accessory genital glands of sheep is not necessarily closely linked to normal histologic appearance.

Animals

Experimental transmission of gastro-intestinal nematodes between sheep (Ovis aries) and Thomson's gazelles (Gazella thomsonii).

Experimental cross-transmission of gastro-intestinal nematodes between Merino sheep (Ovis aries) and Thomson's gazelles (Gazella thomsonii) from similar but separate grazing habitats in Kenya was studied. Cross-transmission did occur with some species but the faecal egg counts of sheep were higher than the gazelles' following infection with larvae isolated from either sheep or gazelles. Of the 11 gastro-intestinal nematodes which became established in gazelles following infection with larvae cultured from nematodes in gazelles, only Haemonchus contortus, Trichostrongylus probolurus and Cooperia hungi were infective for sheep. Following infection with larvae of either sheep or gazelle origin, the H. contortus recovered from the sheep at necropsy were more numerous and had greater average weights, lengths and spicule lengths than those recovered from the gazelles. This would suggest that H. contortus is primarily a sheep parasite. It is concluded that Thomson's gazelles probably would not contribute significantly to the problem of haemonchosis in sheep in areas of shared grazing, unless efforts were being made to eradicate the parasite from sheep, in which case the gazelles would act as a continuing reservoir of infection.

Animals

Mapping of mitochondrial DNA of individual sheep and goats: rapid evolution in the D loop region.

Mitochondrial DNA (mtDNA) from sheep and goat was compared by restriction endonuclease analysis and heteroduplex mapping in the electron microscope. The fragment patterns produced by endonuclease Hae III from three individual sheep and two goat mtDNAs all differed from each other. The three sheep mtDNAs had identical Eco RI and Hind III fragments, but the two goat mtDNA patterns differed from each other as well as from sheep mtDNA. We estimate that each sheep mtDNA differs from each other by 0.5-1% of its nucleotide sequences, the two goat mtDNAs by 1-2%, and there is a 6-11% sequence difference between sheep and goat mtDNAs. We have mapped the Eco RI and Hind III sites of goat and sheep mtDNA and determined the positions of the D loop, which marks the replication origin, relative to the restriction map. The D loops are at homologous positions on the mtDNAs from both species, but the goat D loop is only 75% as long as the sheep D loop. Regions with a high degree of sequence divergence occur at both ends of the D loop. We suggest that a duplication of about 150 base pairs has occurred in the region where the sheep and goat D loops differ in length. We discuss mtDNA evolution in terms of divergence of isolated "mitochondrial DNA clones."

Animals

Chronic copper poisoning in sheep. ii. The distribution of soluble copper-, molybdenum-, and zinc-binding proteins from liver and kidney.

The concentrations of copper, molybdenum, and zinc in the soluble protein fraction from sheep liver and kidney were determined after gel filtration. Samples from grazing sheep as well as from copper poisoned sheep were tested. In normal sheep the copper-binding proteins were separated into 3 different fractions. In copper poisoned sheep, as well as in grazing sheep with high copper concentrations, only 2 main fractions were seen. Molybdenum was only found in the high molecular weight protein fraction. The distribution of the zinc-binding proteins varied according to the degree of copper accumulation. The low molecular weight zinc-binding protein fraction was only seen in sheep with liver copper concentrations lower that 40 mug/g wet weight. In copper poisoned sheep a major part of the kidney copper was found in the low molecular weight protein fraction. At post mortem the bile copper concentrations in the copper poisoned sheep were only 2-4 times higher than those of the control animals.

Animals

3,3',5'-Triiodothyronine (reverse T3) and 3,3',5-triiodothyronine (T3) in fetal and adult sheep: studies of metabolic clearance rates, production rates, serum binding, and thyroidal content relative to thyroxine.

To examine the mechanism(s) responsible for high serum concentration of 3,3',5'-triiodothyronine (reverse T3, rT3) and low serum concentration of 3,3',5-triiodothyronine (T3) in the fetus, we studied metabolic clearance rates (MCR) and production rates (PR) of rT3, T3, and thyroxine (T4) in adult nonpregnant sheep and sheep fetuses in utero. The mean fetal MCR-rT3 was significantly lower than that in adult sheep, and the mean fetal PR-rT3 significantly higher. The mean fetal MCR-T3 was higher than, and the mean fetal PR-T3 similar to that in adult sheep. The mean fetal MCR-T4 and PR-T4 were both significantly higher than the corresponding values in adult sheep. The ratios of mean PR-rT3 to PR-T4 (rT3/T4) were similar in fetal and adult sheep. However, the ratio of mean PR-T3 to PR-T4 (T3/T4) in the fetal sheep was much lower than that in the adult sheep. The low fetal MCR-rT3 was not attributable to high serum binding of rT3. On the basis of the thyroidal content and kinetics of iodothyronines, it was estimated that whereas thyroidal secretion may account for nearly all of serum T3 (or PR-T3) in the fetus and about 50% of serum T3 in adults, it accounts for only about 3% of the serum rT3 (or PR-rT3) in both fetal and adult sheep. The results suggest a) that elevated serum rT3 in the fetus is due to its decreased clearance and increased production by mono-deiodination of T4, and b) that low serum T3 in the fetus is due to its increased clearance and decreased production by mono-deiodination of T4. In addition, on the basis of discordant changes in the production of T3 and rT3 from T4, it appears that there may exist two separate, apparently specific, iodothyronine deiodinating activities--one cleaving the iodine atom at the 5'-position and the other acting in the iodine atom at the 5-position of the T4 molecule; 5'-iodothyronine deiodinating activity is apparently reduced in the fetus.

Aging

Flow and protein composition of intestinal lymph in sheep infected with the enteric nematode, Trichostrongylus colubriformis.

A study of immunoglobulin and albumin concentrations and the flow of intestinal lymph was made in sheep during infection with the parasitic nematode, Trichostrongylus colubriformis. Observations were made on uninfected worm-free sheep, on worm-free sheep undergoing primary infection and on immune sheep undergoing challenge infection. The flow of intestinal lymph and the concentrations of IgG1, IgG2 and IgM in intestinal lymph and IgG2 and IgM in blood plasma remained relatively constant during both primary and challenge infection. The concentration of IgA in intestinal lymph and blood plasma increased as early as day 6 of primary infection and maximum values were observed at day 34. By day 34 of primary infection the concentration of IgG1 in blood plasma was significantly greater than that found in worm-free controls. Plasma IgG1 concentrations in resistant sheep were also significantly greater than those observed in worm-free controls. Challenge infection in immune sheep did not raise the concentration of IgA in intestinal lymph and blood or IgG1 in blood. An indirect haemagglutination test was used to detect antibodies to T. colubriformis. Primary infection did not increase anti-worm antibody titres in either intestinal lymph or serum. Significant antibody titres were present in serum and lymph from immune sheep and were rapidly increased by challenge infection. Most antibody activity in serum was associated with IgM, whereas that in intestinal lymph was associated with IgA. These observations indicate the occurrence of a local antibody response to T. colubriformis in the intestine of immune sheep.

Agglutinins

An immunohematological study of chronic copper toxicity in sheep.

Direct and indirect Coombs tests were performed on six experimentally chronic copper poisoned sheep and on two control sheep. Initially, all sheep were direct Coombs test negative and five of six experimental and one of two control sheep were indirect Coombs test positive. During intoxication, five of six experimental sheep became direct Coombs test positive while controls remained negative. Eluates, prepared from the red cells of three experimental sheep, sensitized normal sheep red cells, as measured by the indirect Coombs test. Similarly prepared eluates from control sheep were negative.

Animals

The effect of route of infection on acquired resistance to Fasciola hepatica in the rat and sheep.

Rats and sheep were infected with Fasciola hepatica by subcutaneous, intramuscular or oral (intraruminal--sheep) inoculation with encysted metacercariae and the development of flukes from these primary infections assessed. Additional rats and sheep similarly infected were challenged with encysted metacercariae orally (rats), or intraruminally (sheep) to assess the level of acquired resistance generated by previous infection by each of the three routes of administration. In both rats and sheep 0--5 per cent, 0--5 per cent and 20--25 per cent of metacercariae given by the subcutaneous, intramuscular or oral (intraruminal--sheep) routes were recovered as flukes in the liver four and 12 weeks after infection of rats, or 17 weeks after infection of sheep. Primary infection of rats with F hepatica by each of the three routes generated strong protection against oral challenge whereas no protection was generated in sheep, irrespective of route of infection.

Administration, Oral

[Occurrence of nematodiasis among sheep and goats].

The spread was studied of sheep and goat nematodirosis in the conditions prevailing in the district of Varna for the 1973-1975 period. Füleborn's method was employed with a total of 24,909 coprosamples taken from the animals as follows: sheep--12,690, weaned lambs--7370, lambs--3355, kids--782, and goats--712. Partial helminthologic postmortem examinations were carried out by the digestive method of 104 sheep, 33 goats, 142 weaned lambs, 96 lambs, and 35 kids. The percent of infected animals was determined on the basis of the coprostudies as follows; lambs--20.9 (per cent), kids--26.6, weaned lambs--54.9, sheep--22.6, goats--24.8. The necroscopic investigations revealed 32.3, 40, 64.8, 32.5, 39.4 per cent, respectively. The average parasite burden in number of helminths was 313 (lambs), 85 (kids), 1517 (weaned lambs), 586 (sheep), and goats--290. Greatest number of Nematodirus parasites was found in weaned lambs--16,000, followed by sheep--2260, lambs--1840, goats--800, and kids--240. As many as 100 per cent Nematodirus carriers were found on a sheep farm in the district. It was also found that the north plains of the district are less infected as against the south parts embracing the northern slopes of the Balkan mountain, and along the course of the Kamchia river. It was found that sheep on the private farm-holdings were more strongly infected than those on the cooperative farms. On the other hand, it was established that on farms where lambs and weaned lambs graze together with the adults the former prove more strongly infected than those that are on isolated grasslands.

Age Factors

Effect of breed-type on carcass weight and composition in sheep.

The relative rate of increase in the carcass and its tissues with increasing empty body weight (EBW) or carcass weight respectively, was studied in male sheep from the Dorset Horn (29), Hampshire (21) and Sudan Desert sheep (31). The rate at which the carcass, muscle and bone increased in weight was the same in all breeds but the Desert sheep deposited fat at a slower rate than the other 2 breeds. At an equally adjusted EBW the Desert sheep had lighter carcasses than the Dorset Horn or Hampshire sheep. Desert sheep had more bone than the other 2 breeds at an equally adjusted cold carcass weight or muscle plus bone weight. At an equally adjusted total carcass fat weight the Desert sheep had significant (P < 0.01) more intermuscular and internal fat but less subcutaneous fat than the other 2 breeds. Future improvement plans of the Desert sheep may be directed towards reducing bone and increasing muscle content of the carcass.

Adipose Tissue

Heterophile antibodies. Part III. Evidence for linkage of high responder activity to sheep red blood cells and the formation of specific antibodies to HBsAg.

Group A, B and O subjects who produce immune antibodies to group A1 or B red blood cells also produce high titer antibodies to sheep red blood cells. Sheep red blood cells appear to possess AB-like as well as non-AB determinants on their surface membranes, each capable of producing and reacting with antibodies of their respective specificities. The antibodies against AB-like determinants preferentially agglutinate A or B cells whereas non-AB-like determinants preferentially stimulate hemolytic antibodies. Human antibodies reacting with these two kinds of determinants on sheep red blood cells may be produced in response to microorganisms possessing very similar factors on their membranes. Individuals who possess AB-like determinants in their secretions, similar to the determinants present on sheep red blood cells (or microorganisms), often make weaker antibodies to these red blood cells. Subjects lacking corresponding anti-sheep inhibitors in their secretions generally produce stronger sheep red blood cell antibodies. There is a positive correlation between the formation of antibodies to HBsAg and strong agglutinating antibodies to sheep red blood cells, indicating that similar determinants may be found on HBsAg virus and on sheep red blood cells. No such correlation was found for anti-tetanus antibodies.

ABO Blood-Group System

A comparison of the voluntary intake and digestion of a range of forages at different times of the year by the sheep and the red deer (Cervus elaphus).

1. Comparisons were made between castrated male Scottish Blackface sheep and red deer (Cervus elaphus) of voluntary forage intake (VFI), digestibility and the mean retention time (MRT) of a particulate-phase marker (103Ru-phenanthroline) in the alimentary tract, when a range of forages: dried-grass pellets, chopped dried grass, fresh-frozen Agrostis-Festuca spp. and heather (Calluna vulgaris, L. Hull) were given at different times of the year. 2. On both the dried-grass-pellet and chopped dried-grass diets the red deer and sheep ate similar quantities. Both species had a higher VFI of dried-grass pellets in July than in November. The sheep digested the dried-grass-pellet diet better than the red deer and this was associated with a longer MRT of the particulate-phase marker in the alimentary tract. 3. The VFI of Agrostis-Festuca spp. and heather by the red deer was twice that of the sheep. The VFI of heather by the sheep increased by 32% between January and April, and the VFI of both the Agrostis--Festuca spp. and heather diets by the red deer increased by 65--70%. The sheep digested the Agrostis--Festuca spp. better than the red deer but the red deer digested the heather slightly better than the sheep. MRT of the particulate-phase marker was greater for the sheep than for the red deer on both the diets. The digestibility and MRT of both diets in the red deer did not decrease with the seasonal increase in VFI, suggesting a possible hypertrophy of the alimentary tract.

Animal Feed

Attempted cross-transmission of coccidia between sheep and goats and description of Eimeria ovinoidalis sp. n.

Attempted infection of 2 young lambs with oocysts of Eimeria christenseni from a goat was unsuccessful. Negative results were obtained also when young kids were fed oocysts of Eimeria ninakohlyakimovae from sheep. There was no difficulty in infecting lambs with the sheep coccidium resembling E. ninakohlyakimovae nor goats with the goat coccidium E. christenseni. Oocysts from the goat measured 38.4 X 26.7 microns, but were easily distinguished from Eimeria ahsata from the sheep by sporocyst size and shape, and from Eimeria ovina by oocyst size. Eimeria ninakohlyakimovae-like oocysts from sheep averaged 23.0 X 18.2 microns and were morphologically indistinguishable from previously reported goat coccidia. Since no cross infections of sheep and goats could be accomplished with oocysts of Eimeria sp. characteristic of one or the other host, I concluded that sheep coccidia previously known as E. ninakohlykimovae are distinct from morphologically similar goat coccidia and therefore constitute a separate species. Since the name E. ninakohlyakimovae was first used for coccidia from the goat, the sheep coccidium is renamed Eimeria ovinoidalis with oocyst structure and endogenous stages similar to those previously described from the sheep.

Animals

The effects of two analogues of arginine-vasopressin (ornithine-vasopressin and desamino-D-arginine-vasopressin) on kidney function in sheep.

The effects of intravenous infusion of ornithine-vasopressin (OVP) and desamino-D-arginine-vasopressin (dDAVP) were studied in normal and hydrated Merino sheep. In normal sheep, OVP resulted in a diuresis, increased urinary sodium and potassium excretion, and a fall in the plasma potassium concentration. Renal plasma flow remained constant but glomerular filtration rate and filtration fraction rose markedly. dDAVP in normal sheep was antidiuretic, but its only significant effect was a small decrease in plasma osmolality. In the hydrated sheep OVP was antidiuretic and resulted in increased urinary excretion of sodium and potassium, and a fall in the plasma potassium level. Renal plasma flow fell, but glomerular filtration and filtration fraction tended to rise. dDAVP in the hydrated sheep was also antidiuretic but urinary sodium and potassium excretion was reduced. Renal plasma flow and glomerular filtration fell, with a small decrease in filtration fraction. These results suggest that the diuretic effect in normal sheep and the electrolyte-excreting effects in both normal and hydrated sheep of OVP are related to the increase in glomerular filtration, which in turn is dependent on the vasopressor activity of the hormone. The increase in glomerular filtration caused by OVP is due to an increase in the filtration fraction of an unchanged renal plasma flow, which could be brought about by an increase in renal efferent arteriolar tone. The effects of hydration of the sheep were the conventional increased urine flow, decreased urine osmolality and decreased solute-free water reabsorption. Sodium and potassium excretion rose slightly and plasma osmolality fell. Renal plasma flow and glomerular filtration both increased with little change in filtration fraction. These effects could be brought about by suppression of endogenous vasopressin and a decrease in both afferent and efferent renal arteriolar tone.

Animals

Rate of flow of digesta and electrical activity of the small intestine in dogs and sheep.

1. Spiking activity of the small intestine in the conscious dog and sheep was recorded continuously from electrodes chronically implanted on the jejunum and summed at intervals of 20 sec. The activity was related to the transit time and flow rate of intestinal contents as estimated by phenol red and by dilution of continuous marker infusions respectively. Also in some sheep the flow of digesta was measured directly from a cannula in the proximal part of the jejunum, and also by use of an electromagnetic flow meter. 2. In the fasted dog and in sheep on a normal diet the intestinal activity was characterized by a migrating myo-electric complex comprising an irregular phase followed by a regular phase. These migrating myo-electric complexes occurred regularly after a period of inactivity at a frequency of 15-20/24 hr. In dogs after feeding, a continuous spiking activity appeared and persisted for periods of 7-8 hr. This was associated with much higher rates of flow and shorter transit times than were observed during fasting. In sheep, continuous spiking activity could be induced by intravenous injection of 5-hydroxytryptophan and this, similarly, was accompanied by a more rapid flow and a shorter transit time than recorded during the control period. 3. In both species the longest transit time occurred when a phenol red bolus was injected during the period of electrical inactivity. Relatively short transit times were observed when the bolus was administered just before the period of regular spiking activity. 4. When relaxation of the bowel was induced by intraperitoneal injection of hypertonic saline there was no spiking activity and the transit time for the infused solution was greatly lengthened, especially in the sheep. A noticeable flow of digestive contents persisted in the dog. 5. In the sheep the intestinal contents flowed intermittently during periods of 10-15 min and at the same frequency as the migrating myo-electric complex. Two thirds of this flow took place in the 4-6 min immediately preceding the periods of irregular spiking activity. 6. It is concluded that in the fasted dog and in the sheep the migrating myo-electric complex controls the pressure gradients on which the flow of intestinal contents depends. This is accomplished in the main by the prolonged phase of irregular spiking activity, and it is suggested that the regular spiking activity which follows it, though not in itself propulsive, serves as a barrier to prevent backflow of digesta into the quiescent part of the intestine. When continuous spiking activity is induced, by feeding in the dog and by injection of 5-hydroxytryptophan in the sheep, no part of the intestine is quiescent and the transit time is shortened by the incessant irregular spiking activity.

5-Hydroxytryptophan

A systematic review and meta-analysis to estimate the global prevalence of leptospirosis in sheep.

Leptospirosis in sheep is a zoonotic concern considering sheep may act as potential reservoirs for Leptospira spp. infection to humans. This study aimed to estimate the pooled prevalence of leptospirosis in sheep worldwide. A comprehensive literature search was conducted across databases following PRISMA guidelines. Meta-analyses were performed using a random effect model in R software (version 4.3.1) to calculate pooled prevalence with 95% confidence intervals (CI). Subgroup analyses were performed based on prevalence types, diagnostic methods and continental regions to explore sources of heterogeneity. A total of 138 studies comprising 54,174 samples and 10,299 positive detections were included in this study. The global pooled prevalence of leptospirosis in sheep was 15.69% (95% CI: 12.69-19.25) with overall heterogeneity (I2) 98%. The prediction interval ranged from 1.09% to 75.91%, indicating wide inter-study variability. The seroprevalence was 16.16% (95% CI: 12.91-20.04) and infection prevalence was 12.98% (95% CI: 8.07-20.22), showing no significant difference (P&#xa0;=&#xa0;0.40). In addition, the prevalence of leptospirosis in sheep differed significantly across diagnostic methods and continents (P&#xa0;<&#xa0;0.01), indicating substantial variation influenced by both methodological and geographical factors. The funnel plot revealed marked asymmetry, suggesting potential publication bias which was confirmed by Egger's regression test (P&#xa0;<&#xa0;0.01). In conclusion, leptospirosis is widely prevalent in sheep globally, with marked geographical and methodological heterogeneity. These findings highlight the epidemiological importance of sheep in leptospirosis transmission and underscore the need for improved surveillance, standardized diagnostic approaches, and targeted control strategies within a One Health framework.

Animals