The postnatal leptin surge in mice is variable in both time and intensity and reflects nutritional status

Background/objectives The murine postnatal leptin surge occurs within the first 4 weeks of life and is critical for neuronal projection development within hypothalamic feeding circuits. Here we describe the influence of nutritional status on the timing and magnitude of the postnatal leptin surge in mice. Methods Plasma leptin concentrations were measured 1–3 times per week for the first 4 weeks of life in C57BL/6J pups reared in litters adjusted to 3 (small), 7–8 (normal), or 11–12 (large) pups per dam fed breeder chow or raised in litters of 7–8 by dams fed high-fat diet (HFD) ad libitum starting either prior to conception or at parturition. Results Mice raised in small litters become fatter than pups raised in either normal or large litters. The leptin surge in small litter pups starts earlier, lasts longer, and is dramatically larger in magnitude compared to normal litter pups, even when leptin concentrations are normalized to fat mass. In mice reared in large litters, weight gain is diminished and the surge is both significantly delayed and lower in magnitude compared to control pups. Pups reared by HFD-fed dams (starting preconception or at parturition) are fatter and have augmented leptin surge magnitude compared to pups suckled by chow-fed dams. Surge timing varies depending upon nutritional status of the pup; the source of the surge is primarily subcutaneous adipose tissue. At peak leptin surge, within each group, fat mass and plasma leptin are uncorrelated; in comparison with adults, pups overproduce leptin relative to fat mass. Plasma leptin elevation persists longer than previously described; at postnatal day 27 mice continue overproducing leptin relative to fat mass. Conclusions In mice, small litter size and maternal HFD feeding during the perinatal period augment the plasma leptin surge whereas large litter size is associated with a delayed surge of reduced magnitude.

Differences in gene expression and variable splicing events of ovaries between large and small litter size in Chinese Xiang pigs

Background Although lots of quantitative trait loci (QTLs) and genes present roles in litter size of some breeds, the information might not make it clear for the huge diversity of reproductive capability in pig breeds. To elucidate the inherent mechanisms of heterogeneity of reproductive capability in litter size of Xiang pig, we performed transcriptome analysis for the expression profile in ovaries using RNA-seq method. Results We identified 1,419 up-regulated and 1,376 down-regulated genes in Xiang pigs with large litter size. Among them, 1,010 differentially expressed genes (DEGs) were differently spliced between two groups with large or small litter sizes. Based on GO and KEGG analysis, numerous members of genes were gathered in ovarian steroidogenesis, steroid biosynthesis, oocyte maturation and reproduction processes. Conclusions Combined with gene biological function, twelve genes were found out that might be related with the reproductive capability of Xiang pig, of which, eleven genes were recognized as hub genes. These genes may play a role in promoting litter size by elevating steroid and peptide hormones supply through the ovary and facilitating the processes of ovulation and in vivo fertilization.

Factors Contributing To The Swimmer Puppy Syndrome Found in Labrador Retrievers

Background Swimmer puppy syndrome is a disease found in neonatal puppies mainly characterized by the inability to stand, but its direct cause is unknown. Since swimmer puppies were observed infrequently but continuously among the Labrador retriever colony at the Hokkaido Guide Dogs for the Blind Association in Japan, based on their birth record and pedigree, factors related to the onset of swimmer puppy syndrome in Labrador retrievers were examined. Results The total number of offspring over seven years was 436, of which 16 were swimmer puppies. Most of the affected puppies except one recovered steadily. As for the swimmer puppies, the litter size was significantly lower, and the body weights on the 10th and 28th day after delivery were significantly higher than the non-symptomatic puppies. These results suggested that the onset may be related to weight gain in the neonatal stages due to a small litter size. According to the genetic analysis, 26 ancestors common to the affected individuals were confirmed, but the causative individual could not be identified with the inbreeding coefficient. The heritability of the swimmer-puppy onset trait was 0.80, and the heritability for the the 10th -day body-weight trait was equally high at 0.78, both of which strongly suggest genetic involvement. Conclusions In this study, the onset of swimmer puppy syndrome in the Labrador retrievers was associated with litter size and early weight gain, and result of study suggests that genetic influence might be involved.

High laboratory mouse pre-weaning mortality associated with litter overlap, advanced mother age, small and large litters

High and variable pre-weaning mortality is a persistent problem among the main mouse strains used in biomedical research. If a modest 15% mortality rate is assumed across all mouse strains used in the EU, approximately 1 million more pups must be produced yearly to compensate for those which die. A few environmental and social factors have been identified as affecting pup mortality, but optimizing these factors does not cease the problem. This study is the first large study to mine data records from 219,975 pups from two breeding facilities to determine the major risk factors associated with mouse pre-weaning mortality. It was hypothesized that litter overlap (i.e. the presence of older siblings in the cage when new pups are born), a recurrent social configuration in trio-housed mice, is associated with increased newborn mortality, along with high mother age, large litter size, as well as a high number and age of older siblings in the cage. The estimated probability of pup death was two to seven percentage points higher in cages with compared to those without litter overlap. Litter overlap was associated with an increase in percentage of litter losses of 19% and 103%, respectively, in the two breeding facilities. Increased number and age of older siblings, high mother age, small litter size (less than four pups born) and large litter size (over 11 pups born) were associated with increased probability of pup death. Results suggest that common social cage configurations at breeding facilities are dangerous for the survivability of young mouse pups. The underlying mechanisms and strategies to avoid these situations should be further investigated.

Genetic Association between Swine Leukocyte Antigen Class II Haplotypes and Reproduction Traits in Microminipigs

The effects of swine leukocyte antigen (SLA) molecules on numerous production and reproduction performance traits have been mainly reported as associations with specific SLA haplotypes that were assigned using serological typing methods. In this study, we intended to clarify the association between SLA class II genes and reproductive traits in a highly inbred population of 187 Microminipigs (MMP), that have eight different types of SLA class II haplotypes. In doing so, we compared the reproductive performances, such as fertility index, gestation period, litter size, and number of stillbirth among SLA class II low resolution haplotypes (Lrs) that were assigned by a polymerase chain reaction-sequence specific primers (PCR-SSP) typing method. Only low resolution haplotypes were used in this study because the eight SLA class II high-resolution haplotypes had been assigned to the 14 parents or the progenitors of the highly inbred MMP herd in a previous publication. The fertility index of dams with Lr-0.13 was significantly lower than that of dams with Lr-0.16, Lr-0.17, Lr-0.18, or Lr-0.37. Dams with Lr-0.23 had significantly smaller litter size at birth than those with Lr-0.17, Lr-0.18, or Lr-0.37. Furthermore, litter size at weaning of dams with Lr-0.23 was also significantly smaller than those dams with Lr-0.16, Lr-0.17, Lr-0.18, or Lr-0.37. The small litter size of dams with Lr-0.23 correlated with the smaller body sizes of these MMPs. These results suggest that SLA class II haplotypes are useful differential genetic markers for further haplotypic and epistatic studies of reproductive traits, selective breeding programs, and improvements in the production and reproduction performances of MMPs.

Changes in Ovary Transcriptome and Alternative splicing at estrus from Xiang pigs with Large and Small Litter Size

Background/AimsLitter size is one of the most important reproductive traits in pig breeding, which is affected by multiple genes and the environment. Ovaries are the most important reproductive organs and have a profound impact on the reproduction efficiency. Therefore, genetic differences in the ovaries may contribute to the observed differences in litter size. Although QTLs and candidate genes have been reported to affect the litter size in many pig breeds, however, the findings cannot elucidate the marked differences of the reproductive traits between breeds. The aim of present work is to elucidate the mechanisms of the differences for the reproductive traits and identify candidate genes associated with litter size in Xiang pig breed.MethodsThe changes in ovary transcriptome and alternative splicing were investigated at estrus between Xiang pigs with large and small litter size by RNA-seq technology. The RNA-seq results were confirmed by RT-qPCR method.ResultsWe detected 16,219 - 16,285 expressed genes and 12 types of alternative splicing (AS) events in Xiang pig samples. A total of 762 differentially expressed genes were identified by XL (Xiang pig group with larger litter size) vs XS (Xiang pig group with small litter size) sample comparisons. A total of 34 genes were upregulated and 728 genes were downregulated in XL ovary samples compared with the XS samples. Alternative splicing (AS) rates in XL samples were slightly lower than that observed in XS samples. Most of differentially expressed genes were differentially regulated on AS level. Eleven candidate genes were potentially identified to be related to Xiang pig fecundity and litter size, which may be closely related to the gonad development, oocyte maturation or embryo quality.ConclusionThe significant changes in the expression of the protein-coding genes and the level of alternative splicing in estrus ovarian transcriptome between XL and XS groups probably are the molecular mechanisms of phenotypic variation in litter size.

Serum progesterone and oestrone sulphate concetrations for monitoring fertility in Sows

Blood samples were taken from 161 sows the days 19-21 (serum progesterone assessments), from 306 sows on days 24-30 (serum oestrone sulphate assessments) and from 150 sows on day 20 (serum progesterone assessments) and on days 26-29 (serum oestrone sulphate assessments) after service. Actual farrowing or abortion and signs of return to oestrus were used as criteria for pregnancy and non-pregnancy, respectively. Litter size was also recorded at each farrowing. The results showed that the overall accuracy of progesterone and oestrone sulphate for predicting pregnant sows was 90.7% and 97.2%, respectively. The highest accuracy of oestrone sulphate (100%) was noticed on days 27 and 28 after service. The overrall accuracy of the combination of both progesterone and oestrone sulphate assessments to detect pregnant sows was 97% and to detect non-pregnant sows was 100%. Significant correlation coefficients between serum oestrone sulphate concentration and litter size were found on days 24,26,27, 28,29 and 30, but the highest correlation coefficient was noticed on day 28 after service (r=0.51, Ρ, 0.001). Moreover, it was also found that mean litter size was significantly higher (P <0.05). in sows with serum oestrone sulphate concentrations > 1 ng/ml compared with concentrations < 1 ng/ml from day 26 up to day 30 after service. It is concluded that serum progesterone assessment helps in the determination of the non-pregnant sows early enough for problems related to failure of fertilization to be promptly dealt with. Serum oestrone sulphate concentration on day 28 after service can be used as an indicator of conception, as a predictor of small litter size and also can help in the estimation of embryonic mortality. The combination of these two assessments, in addition to their value in pregnancy diagnosis, can be useful in identifying concurrent reproductive problems in units with sub-optimal productivity.