Increased Litter Size Research Articles

Supplementing newborn intrauterine growth restricted piglets with a bolus of porcine colostrum raises rectal temperatures one degree Celsius.

Hyperprolific sows have increased litter sizes but also result in more piglets that have been exposed to intrauterine growth restriction (IUGR). These IUGR piglets are likely to have a low rectal temperature and lower blood glucose levels compared with normal piglets at birth. Therefore, we hypothesized that a colostrum bolus at birth and/or heat from an external source would have a positive effect on blood glucose levels, rectal temperatures, and growth up to 8 h postpartum. In addition, liver glycogen and blood values at 8 h were investigated. Eighty-four piglets were classified at birth (time = 0) as IUGR based on their head morphology and randomly allocated to 1 of 4 treatments ( = 21) in a 2 × 2 factorial arrangement: 1) with or without a porcine colostrum bolus (12 mL/kg BW at birth) and 2) with sow or isolated from sow with external heat. Piglets were removed from the sow before they had suckled and were numbered and dried, and initial whole-blood glucose, rectal temperature, and BW were recorded. Piglets in the 2 treatments isolated from sow were placed under a heating lamp (150 W) with a temperature range of 35 to 39°C. Rectal temperatures, glucose, and BW were measured again at 1, 2, 4, 6, and 8 h after birth, and a final plasma sample and organs (liver and brain) were removed at 8 h. There was a time × colostrum bolus interaction ( = 0.026) and a time × sow interaction ( < 0.001) for whole-blood glucose. The piglets that were given a bolus had greater glucose levels after 1 h postpartum (time = 1 h) than piglets without a bolus at birth, but from time = 2 h and onward, there was no difference ( > 0.05). There was a time × colostrum bolus interaction ( < 0.001) and a time × sow interaction ( < 0.001) on rectal temperatures. One hour after birth, the piglets with a bolus had a greater rectal temperature compared with piglets without a bolus (37.5 vs. 36.6°C; < 0.001) and the piglets that had been isolated from the sow had a greater rectal temperature compared with the 2 treatments with sows (37.8 vs. 36.3°C; < 0.001). Four hours after birth, rectal temperature was not affected by treatments. In conclusion, both heat and a colostrum bolus increased rectal temperature by 1°C an hour after birth. However, after 4 h, no differences were found between the treatments. Interventions to help IUGR piglets postpartum most likely need to be frequent to have any effect on whole-blood glucose, rectal temperatures, and BW over the first 8 h.

Issues and opportunities to capitalize on increased litter size in hill country sheep farming systems—a New Zealand perspective

Issues and opportunities to capitalize on increased litter size in hill country sheep farming systems—a New Zealand perspective

Influence of dietary fat source on sow and litter performance, colostrum and milk fatty acid profile in late gestation and lactation.

The objective of this study was to investigate the effects of dietary supplementation with various fat sources (3.8-3.9% of diet) during late pregnancy and lactation on the reproductive performance, fatty acids profile in colostrum, milk and serum of sow progeny. A total of 80 multiparous sows were randomly fed a control (adding no oil), palm oil (PO), fish oil (FO) or soybean oil (SO) supplemented diet from 90days of pregnancy to weaning. Supplementation of FO increased litter size of weak piglets, compared with the control-fed sows (P<0.05). Dietary FO and SO supplementation, enhanced the weaning survival rate, litter weaning weight, litter weight gain and fat content in milk (P<0.05). The highest immunoglobulin (Ig)G and IgM levels in colostrum and milk were observed in the FO group (P<0.05). Meanwhile, the highest concentration of C22:5 (n-3) and C22:6 (n-3) in colostrum, milk and piglet serum was observed in the FO group (P<0.05). Taken together, dietary inclusion of FO or SO improved growth performance of nursing piglets by increasing milk fat output, and FO consumption by sows might benefit the piglets via increasing n-3 polyunsaturated fatty acid availability and immunoglobulins (IgG and IgM) secretion.

Genetic screening of FecB, FecXG and FecXI mutations and their linkage with litter size in Barki and Rahmani sheep breeds.

Characterization of fecundity genes offers the opportunity to improve production efficiency, and the consequent increase in litter size in livestock industry, through utilizing them in breeding programs. The main objective of this study was to detect the BMPR-IB, BMP15 and GDF9 gene mutations and to investigate whether these mutations are associated with litter size in Egyptian sheep breeds. To achieve this goal, 73 adult ewes representing Barki (n=33) and Rahmani (n=40) breeds were used. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) screening approach was used to detect the presence of FecB, FecXG and FecXI mutations in the two selected breeds. Results of this study showed that the three different candidate gene mutations, namely FecB, FecXG and FecXI are not present among these selected populations of the Egyptian breeds. Further studies regarding other mutations and/or other genes, which may influence ovulation rate, should be carried out to determine the type and mode of inheritance of such genes in Egyptian sheep breeds.

Trade-offs between litter size and offspring fitness in domestic pigs subjected to different genetic selection pressures

Artificial selection of the domestic pig (Sus scrofa domesticus) offers a useful model for investigating changes in behaviour associated with reproductive trade-offs between litter size and fitness of offspring. The aim of this study was to evaluate effects of litter size on teat stimulation, sibling competition, and pre-weaning survival and growth in three populations of domestic pigs subjected to different selection pressures (a maternal line selected for high reproductive investment, a paternal line selected for meat production traits, and a crossbred line). We predicted that, with increasing litter size, piglets would spend more time in udder massage, be less likely to gain access to a teat during milk letdown and, if surviving to weaning, have lower, more variable body weights. We also predicted that maternal line sows would wean more piglets of higher weight, despite larger litter sizes, than paternal line sows. Sows (maternal line, n=12, paternal line, n=12, crossbred line, n=14) were loose-housed with their litters in individual farrowing pens. We collected data on piglet behaviour during nursings at 1day of age, when sibling competition was expected to be most intense. Piglets were weaned at 35days of age, when they were weighed and cumulative mortality was calculated. As predicted, piglets in larger litters spent more time in pre- and post-letdown udder massage (P=0.050 and P<0.001, respectively). In larger litters, more piglets survived to weaning (P=0.002), but at a cost of a lower proportion of nursings with letdown (P<0.001), longer nursing intervals on average (P=0.018), more piglets without a functional teat at letdown (P<0.001), an increased risk of mortality due to starvation (P<0.001) and crushing (P=0.002), and lower (P=0.039), more variable (P=0.002) body weights at weaning. In the maternal line, nursing intervals lengthened with increasing litter size (litter size×breed: P<0.001) despite more post-letdown udder massage (P<0.001), and mortality due to crushing rose with increasing litter size (P<0.001), without differential increments in number, weight or weight uniformity of weaned piglets with increasing litter size between breeds (litter size×breed: P>0.1). Our results suggest that further artificial selection for larger litters in maternal lines will be unsustainable because increments in the number of piglets weaned have increasing costs (e.g. sibling competition, mortality, uneven growth) that compromise piglet welfare and fitness.

236 Got colostrum? Effect of diet and feeding level on piglet colostrum intake and piglet quality

The objective of the study was to determine the effect of late gestation diet and feeding level on piglet colostrum intake and piglet quality. Second parity, composite Landrace × Large White sows (n = 61) were housed at the North Carolina Department of Agriculture Tidewater Research Station. At d 104 of gestation sows were randomly allocated by body condition to one of two diets, gestation (GEST) or lactation (LACT), and one of three feeding levels (1.5, 3.0, or 4.5 kg/d) in a 2 × 3 factorial design. Experimental diets were fed until farrowing. The GEST diet contained 2979 Kcal/kg ME, 0.58 SID lysine and the LACT diet contained 3322 Kcal/kg ME, 0.99 SID lysine and 2.5% added fat. At birth, piglets were individually identified and weighed (BWT). Piglets were again weighed at 24 h of age (WT24) and at 21 d of age (WWT). Colostrum intake (COLOSTRUM) was estimated as WT24- BWT. Piglet survival was calculated as litter size at weaning ÷ total number born. Data analysis was completed in SAS using PROC GLM. Fixed effects included diet, feeding level, and a covariate of litter size for all traits. Sow was the experimental unit. Average litter size at birth, 24 h, and weaning were 13.11, 12.49, and 11.05, respectively. Average piglet BWT, COLOSTRUM, and WWT were 1.16 kg, 111 g, and 5.63 kg, respectively. Total litter COLOSTRUM was not associated (P > 0.05) with litter size. Hence on a piglet basis, a one piglet increase in litter size reduced (P < 0.01) average piglet COLOSTRUM by 12.8 g. A 1 d increase in gestation length improved (P < 0.05) average piglet COLOSTRUM by 8.4 g. In relation to dietary treatments, average BWT did not differ (P > 0.05) between diets or feeding levels. Yet average COLOSTRUM was greater (P < 0.01) for sows fed LACT compared to those fed GEST (127 vs. 96 g). A 1 kg increase in feeding level increased (P = 0.05) average piglet COLOSTRUM by 9 g. Average piglet WWT was heavier (P < 0.01) for sows fed LACT compared to those fed GEST (5.84 vs. 5.45 kg). Both BWT CV and WWT CV were lower (P < 0.05) for sows fed LACT compared to those fed GEST. Sows fed LACT had similar (P > 0.05) piglet survival to those fed GEST (87.3 vs. 84.2%, respectively). Results showed, regardless of feeding level, feeding a lactation diet the last 10 d of gestation reduced litter variation, enhanced piglet colostrum intake and improved piglet weaning weights.

Comparable cortisol, heart rate and milk let-down in nurse sows and non-nurse sows

Increasing litter size in hyperprolific sows has led to the need for management systems for surplus piglets, one of which is the use of nurse sows. The aim of this study was to investigate physiological changes in salivary cortisol, heart rate and number of milk let-downs in nurse sows compared to non-nurse sows. Sows were divided into three treatments: 1) control (non-nurse) sows nursed their own piglets until weaning at 26 days of age; 2) nurse1 sows had their own piglets removed and replaced with newborn piglets (between 6−24h old) at Day 7, these were weaned at Day 33 of the sow's lactation period and 3) nurse2 sows weaned their own piglets at Day 21 and received a litter of 7day old piglets from a nurse1 sow. These new piglets were weaned at Day 40 of the nurse2 sow's lactation period. Saliva samples were collected for cortisol analyses and the sows were fitted with pulse belts to monitor heart rate. Cameras were placed above the pens to record milk let-downs. Overall, there was no influence of treatment on salivary cortisol, heart rate or the number of milk let-downs/h. There was an effect of time as cortisol levels fell throughout lactation (P<0.001), and heart rate increased (P<0.001). Nurse1 sows had a lower cortisol concentration on Day 31 compared to Day 24 (P<0.028). The same was found for nurse2 sows, where the salivary cortisol concentration on Day 31 and Day 38 was significantly lower than on Day 24 (P<0.001). The present study found no differences in short-term (when the sows received new piglets) or long-term (throughout the lactation period) cortisol and heart rate measurements between different treatments. In addition, the frequency of milk let-down/h was the same for nurse sows as for non-nurse sows.

The Evolutionary Economics of Embryonic-Sac Fluids in Squamate Reptiles.

The parchment-shelled eggs of squamate reptiles take up substantial water from the nest environment, enabling the conversion of yolk into neonatal tissue and buffering the embryo against the possibility of subsequent dry weather. During development, increasing amounts of water are stored in the embryonic sacs (i.e., membranes around the embryo: amnion, allantois, and chorion). The evolution of viviparity (prolonged uterine retention of developing embryos) means that embryonic-sac fluid storage now imposes a cost (increased maternal burdening), confers less benefit (because the mother buffers fetal water balance), and introduces a potential conflict among uterine siblings (for access to finite water supplies). Our data on nine species of squamate reptiles and published information on three species show that the embryonic-sac fluids comprise around 33% of neonatal mass in viviparous species versus 94% in full-term eggs of oviparous squamates. Data on parturition in 149 vipers (Vipera aspis, a viviparous species) show that larger offspring store more fluids in their fetal sacs and that an increase in litter size is associated with a decrease in fluid-sac mass per offspring. Overall, the evolutionary transition from oviparity to viviparity may have substantially altered selective forces on offspring packaging and created competition among offspring for access to water reserves during embryonic development.

Estimation of risk factors associated with difficult birth in ewes

In eight closely recorded Australian Merino and crossbred sheep flocks, all lamb deaths were examined and the cause of deaths identified if possible. Dystocia was identified as one of the major causes of lamb death and this study examined factors that could be used to identify ewes at high risk of dystocia, either to avoid dystocia or to assist with early intervention where possible. Dystocia was least common in lambs of ~4.8 kg, but there was a higher risk at both lower and higher birthweights. Dystocia with both low and high birthweight was more common in older ewes, ranging from negligible low birthweight dystocia in ewes less than 3 years old at lambing, to 5% in older ewes. Low birthweight dystocia increased with increasing litter size, with 40% dystocia in ewes at least 4 years of age with triplets. In contrast, high birthweight dystocia was not affected by litter size. A previous record of low birthweight dystocia was a risk factor for future low birthweight dystocia, but the same relationship was not observed for high birthweight dystocia. A high lambing ease score (difficult birth) with high birthweight was a risk factor for future high birthweight dystocia, but this was not the case for low birthweight dystocia. These differences between the risk factors for low and high birthweight dystocia suggest that they have different causes. High ewe liveweight and condition score during pregnancy may be additional indicators of the risk of dystocia, particularly for ewes with high liveweight in the first 60 days of pregnancy. For most ewes dystocia was difficult to predict, but there was a small proportion of ewes with a very high risk of dystocia and if these could be identified in advance they could be monitored much more closely than the rest of the flock.

Genetic analysis of teat number in pigs reveals some developmental pathways independent of vertebra number and several loci which only affect a specific side

BackgroundNumber of functional teats is an important trait in commercial swine production. As litter size increases, the number of teats must also increase to supply nutrition to all piglets. Therefore, a genome-wide association analysis was conducted to identify genomic regions that affect this trait in a commercial swine population. Genotypic data from the Illumina Porcine SNP60v1 BeadChip were available for 2951 animals with total teat number (TTN) records. A subset of these animals (n = 1828) had number of teats on each side recorded. From this information, the following traits were derived: number of teats on the left (LTN) and right side (RTN), maximum number of teats on a side (MAX), difference between LTN and RTN (L − R) and absolute value of L − R (DIF). Bayes C option of GENSEL (version 4.61) and 1-Mb windows were implemented. Identified regions that explained more than 1.5% of the genomic variation were tested in a larger group of animals (n = 5453) to estimate additive genetic effects.ResultsMarker heritabilities were highest for TTN (0.233), intermediate for individual side counts (0.088 to 0.115) and virtually nil for difference traits (0.002 for L − R and 0.006 for DIF). Each copy of the VRTN mutant allele increased teat count by 0.35 (TTN), 0.16 (LTN and RTN) and 0.19 (MAX). 15, 18, 13 and 18 one-Mb windows were detected that explained more than 1.0% of the genomic variation for TTN, LTN, RTN, and MAX, respectively. These regions cumulatively accounted for over 50% of the genomic variation of LTN, RTN and MAX, but only 30% of that of TTN. Sus scrofa chromosome SSC10:52 Mb was associated with all four count traits, while SSC10:60 and SSC14:54 Mb were associated with three count traits. Thirty-three SNPs accounted for nearly 39% of the additive genetic variation in the validation dataset. No effect of piglet sex or percentage of males in litter was detected, but birth weight was positively correlated with TTN.ConclusionsTeat number is a heritable trait and use of genetic markers would expedite selection progress. Exploiting genetic variation associated with teat counts on each side would enhance selection focused on total teat counts. These results confirm QTL on SSC4, seven and ten and identify a novel QTL on SSC14.

Sow-level risk factors for stillbirth of piglets in organic sow herds

In Danish organic pig production, one-third of total born piglets die before weaning, and stillbirth has previously crudely been estimated to account for 27% of the total preweaning mortality. The objective of this study was to evaluate season, litter size, parity and body condition of the sow as risk factors for stillbirth in nine commercial Danish organic pig herds. The study was conducted over a 1-year period, and the data included registrations on 5170 farrowings with 82 906 total born piglets. The average number of total born piglets per litter was 16.0, and the number of stillborn piglets per litter was 1.1. A significant effect of season was seen with an odds ratio for stillbirth of 1.15 during summer (May to August) compared with the remaining part of the year. A non-linear effect of litter size was seen where an increase in litter size from 11 to 16 resulted in an odds ratio of stillbirth of 1.11. An increase in litter size from 16 to 21 resulted in an odds ratio of stillbirth of 1.45. A significant interaction between body condition and parity was present. In first parity sows, an increase in body condition score from 2 (thin) to 3 (moderate) and from 3 to 4 (fat) increased the probability of stillbirth with an odds ratio of 1.23 and 1.36, respectively. In sows with parity above 4, an increase in body condition score from 2 to 3 and from 3 to 4 decreases the probability of stillbirth with an odds ratio of 0.68 and 0.79, respectively. In conclusion, increasing litter size and being born during the summer months of May to August were found to be risk factors for stillbirth. Furthermore, an interaction between body condition and parity showed that thin sows with parity above 4 had a substantially increased risk of stillbirth compared with normal and fat sows with parity above 4. In contrast, for parity 1 sows risk of stillbirth was increased in fat sows.

Sow and piglet factors determining variation of colostrum intake between and within litters

Colostrum intake has a short- and long-term beneficial impact on piglet performance and mortality. Sows’ colostrum production and piglets’ colostrum intake are limited and highly variable. The present study investigated sow and piglet factors explaining the variation of colostrum intake between and within litters. The CV for colostrum intake and birth weight (BWb) of all piglets within a litter was calculated to evaluate the variation of colostrum intake and BWb within a litter (colostrum and litter BWb heterogeneity, respectively). A total of 1937 live-born piglets from 135 litters from 10 commercial herds were included. Colostrum intake per piglet averaged 371±144 g and was affected by breed (P=0.02). It was lower when oxytocin was administered to the sow during parturition (P=0.001) and with increased litter size (P<0.001). It was higher when the interval between birth and first suckling decreased (tFS, P<0.001). Colostrum intake was positively influenced by BWb (P<0.001) and this association was more pronounced in piglets from Topigs (P=0.03) and Hypor (P=0.03) sows compared with piglets from Danbred sow breeds. The positive relationship between colostrum intake and BWb was more pronounced when tFS lasted longer (P=0.009). Heterogeneity in colostrum intake averaged 31±11%, it increased when oxytocin was applied during farrowing (P=0.004) and when stillbirth occurred (P=0.006). Colostrum heterogeneity was positively associated with litter size (P<0.001) and litter BWb heterogeneity (P=0.01). The positive relationship between colostrum and litter BWb heterogeneity was more pronounced when oxytocin was applied during farrowing (P=0.04). The present study demonstrated that oxytocin should be used cautiously in sows during farrowing. Farrowing and colostrum management should prevent or counteract the adverse influences of stillbirth, large and heterogeneous litters on colostrum intake and colostrum heterogeneity. The study also confirmed the expected association between BWb and colostrum intake and indicated that the impact of BWb on colostrum intake was different among breeds (Hypor v. Danbred) and dependent on piglets’ latency to first suckling. Hence, colostrum management should focus on low birth weight piglets, especially in some breeds, and low colostrum intake in low birth weight piglets can be counteracted by shortening the tFS.

Sow dimensions increase with increasing parity but not with increasing litter size

Sow dimensions increase with increasing parity but not with increasing litter size

Sows with high milk production had both a high feed intake and high body mobilization

Selection for increased litter size have generated hyper-prolific sows that nurses large litters, however limited knowledge is available regarding the connection between milk production, feed intake and body mobilization of these modern sows. The aim of the current study was to determine what characterized sows with high milk production and nursing large litters, differences between sows of different parities and effects of lactational performance on next reproductive cycle. In total 565 sows (parity 1 to 4) were studied from 7 days before farrowing until weaning. On day 2 postpartum litters were standardized to 14 piglets. Weight and back fat thickness of sows were measured at day 7 prepartum, day 2 postpartum and at weaning. Litters were weighed at day 2 and at weaning. Pearson correlation coefficients between variables were calculated and regression models were developed. The average daily feed intake (ADFI) of the sows was 6.1±1.1 kg/day, average daily gain (ADG) of the litter was 2.92±0.53 kg/day and sows weaned 13.0±1.1 piglets. First parity sows generally had a lower ADFI and milk production and a decrease in total born piglets in next litter compared with parity 2 to 4 sows, which could be explained by a relatively higher proportion of their body reserves being mobilized compared with multiparous sows. The ADG of the litter was positively related by ADFI of the sows, litter size and BW loss and increasing the ADFI with 1 kg/day throughout lactation likely increased the ADG of the litter with 220 to 440 g/day in parity 1 to 4, respectively. Increasing the ADFI by 1 kg/day reduced the BW loss with 6.6 to 13.9 kg of parity 1 to 4 sows, respectively, during lactation, whereas increasing the average milk yield with 1 kg/day raised the BW loss with 4.3 to 21.0 kg of the four parities during lactation. The number of total born piglets in the next litter was positively related to the number of piglets born in the previous litter. In conclusion, both a high feed intake and a high mobilization of body reserves was a prerequisite for a high milk production. The sows might be very close to the physical limit of what they can ingest and future research should therefore, focus on optimizing the dietary energy and nutrient concentrations of diets for lactating hyper-prolific sows and herein distinguish between primiparous and multiparous sows.

Faithful or not: direct and indirect effects of climate on extra-pair paternities in a population of Alpine marmots.

Despite being identified an area that is poorly understood regarding the effects of climate change, behavioural responses to climatic variability are seldom explored. Climatic variability is likely to cause large inter-annual variation in the frequency of extra-pair litters produced, a widespread alternative mating tactic to help prevent, correct or minimize the negative consequences of sub-optimal mate choice. In this study, we investigated how climatic variability affects the inter-annual variation in the proportion of extra-pair litters in a wild population of Alpine marmots. During 22 years of monitoring, the annual proportion of extra-pair litters directly increased with the onset of earlier springs and indirectly with increased snow in winters. Snowier winters resulted in a higher proportion of families with sexually mature male subordinates and thus, created a social context within which extra-pair paternity was favoured. Earlier spring snowmelt could create this pattern by relaxing energetic, movement and time constraints. Further, deeper snow in winter could also contribute by increasing litter size and juvenile survival. Optimal mate choice is particularly relevant to generate adaptive genetic diversity. Understanding the influence of environmental conditions and the capacity of the individuals to cope with them is crucial within the context of rapid climate change.

Growth differentiation factor 9 gene variants in Sudanese desert sheep ecotypes

Certain variants in the growth differentiation factor 9 ( GDF9 ) gene have major effects on the ovulation rate in sheep. The aim of this study was to analyse GDF9 variability in the Sudanese desert sheep ecotypes Ashgar, Dubasi and Watish, and to test identified variants for association with litter size. For this purpose, ewes of these ecotypes with litter size records for at least two litters were sampled. The complete GDF9 exon 2 was sequenced in a total of 28 ewes. An additional variant in exon 1 (c260G>A) was genotyped by restriction-length polymorphism analysis in 97 ewes. Differences in genotype and allele frequencies of polymorphic positions between two groups differing in litter size (only a single lamb versus more than a single lamb) were tested for significance using Fisher's exact test. GDF9 exon 2 variants c.477G>A and c.721G>A and exon 1 variant c.260G>A were found to be polymorphic in all three sheep ecotypes. Exon 2 variants c.471C>T and c.978 A>G were polymorphic in at least one ecotype. No significant associations were observed between allele and genotype frequencies of identified variants and litter size. This suggests that GDF9 variants influencing ovulation are absent in these Sudanese sheep ecotypes, and therefore cannot be used to increase litter size within this population of sheep. Keywords: Ashgar, Dubasi, fecundity, litter size, ovine fertility, Watish

Nutrição de leitões neonatos: importância da suplementação

The swine industry has shown a great technological progress during the last years, especially due to major advances in genetics. A higher number of piglets produced per litter and lower individual weights has been observed, which increased health challenges. The increasing litter size also reduces uniformity at birth by increasing the frequency of small piglets, which can increase the competition between littermates for colostrum and milk. In addition, all piglets have the natural challenge of facing the control of thermoregulation, having low reserves of glucose and fat at birth. This makes piglets rely almost exclusively on colostrum and milk intake for their survival. These factors may lead to an increase in piglet mortality, which mainly occurs in the first three days of life and represents one of the biggest issues facing the pork industry. The supply of energy sources becomes important in order to enhance the immunity development and the performance of young piglets. The purpose of this review is to present the potential use of different energy sources to promote adequate supplementation, reducing mortality and improving the performance of newborn piglets.

Melatonin improves age-induced fertility decline and attenuates ovarian mitochondrial oxidative stress in mice.

Increasing evidence shows that melatonin protected against age-related mitochondrial oxidative damage. However, the protective effects of melatonin against ovarian aging has not been explored. Young Kunming females (aged 2–3 months) were fed with melatonin added to drinking water for 6 or 12 months (mo). We found that long-term (12 mo) melatonin treatment significantly reduced ovarian aging, as indicated by substantial increases in litter size, pool of follicles, and telomere length as well as oocyte quantity and quality. Melatonin treatment suppressed ovarian mitochondrial oxidative damage by decreasing mitochondrial reactive oxygen species (mROS) generation, inhibiting apoptosis, repressing collapse of mitochondrial membrane potential and preserving respiratory chain complex activities. Female mice fed with melatonin had enhanced mitochondrial antioxidant activities, thus reducing the risk of mitochondrial oxidative damage cause by free radicals. Notably, melatonin treatment enhanced SIRT3 activity but not the protein expression level, and increased the binding affinity of FoxO3a to the promoters of both superoxide dismutase 2 (SOD2) and catalase (CAT). In conclusion, melatonin exerted protection against aging-induced fertility decline and maintenance of mitochondrial redox balance.

OP.5D.01] INHIBITON OF TNF-ALPHA SIGNALLING USING ETANERCEPT IMPROVES DEFICIENT UTERINE ARTERY REMODELLING AND PREGNANCY OUTCOME IN THE STROKE PRONE SPONTANEOUSLY HYPERTENSIVE RAT

Objective: Impaired vascular remodelling has been extensively studied in pre-eclampsia but little is known about adaptation of the cardiovascular (CV) system to pregnancy in women with chronic hypertension. We have previously characterised the stroke prone spontaneously hypertensive rat (SHRSP) as a model of deficient uterine artery remodelling and identified an increase in pro-inflammatory TNF α relative to the normotensive WKY strain during pregnancy. Design and method: SHRSP were treated with etanercept (0.8 mg/kg) or vehicle at gestational day (GD) 0, 6, 12 and 18. Animals were sacrificed at GD18. SHRSP, SHRSP treated with etanercept (ETN) and WKY (n=6) were used for vascular studies. An independent set of animals (n = 6) were used for flow cytometry analysis. Results: Etanercept significantly reduced systolic blood pressure in the SHRSP after GD 10 (δSBP GD 10–21 SHRSP 12.0 ± 4.17 vs. ETN 25.8 ± 4.27 mmHg; p < 0.05). Characterisation of uteroplacental blood flow using Doppler showed that etanercept significantly increased uterine artery diastolic blood flow and significantly reduced resistance index relative to SHRSP (SHRSP 0.79 ± 0.02 vs. ETN 0.61 ± 0.02 resistance index; p < 0.01). Analysis of GD18 uterine arteries using pressure and wire myography showed that etanercept did not change the size of the uterine arteries; but significantly reduced uterine artery contractile ability (SHRSP 57.3 ± 8.75 vs. ETN 35.2 ± 2.19 kPa; p < 0.01) and increased carbachol response (SHRSP 13.8 ± 3.8 % vs. ETN 40.1 ± 3.25 %; p < 0.05). Etanercept significantly increased litter size in the SHRSP (SHRSP 7.80 ± 0.44 vs. ETN 12.75 ± 0.94 fetuses), reduced resorption frequency (SHRSP 66.7% vs. ETN 25.0% dams with resorption) and decreased premature glycogen cell loss from the placenta. We sought to identify the source of excess TNFα in the SHRSP. Inflammatory natural killer (NK) cells (CD3- CD161+) were significantly increased in the SHRSP relative to the WKY in the placenta (WKY 11.6 ± 2.39 vs. SHRSP 659.8 ± 201.2 cells/mg; p < 0.01). Etanercept significantly reduced the number of NK cells in the placenta of the SHRSP (SHRSP 659.8 ± 201.2 vs. ETN 148.0 ± 12.62 cells/mg; p < 0.01). Conclusions: Etanercept improves abnormal uterine artery function in the SHRSP with beneficial effects on pregnancy. Excess TNFα production in this model may come from increased inflammatory NK cells.

Abstract 046: The Role of Tumor Necrosis Factor α and Natural Killer Cells in Uterine Artery Function During Pregnancy in the Stroke Prone Spontaneously Hypertensive Rat

Objective: We have previously characterised the stroke prone spontaneously hypertensive rat (SHRSP) as a model of deficient uterine artery remodelling and identified an increase in pro-inflammatory TNFα relative to the normotensive WKY strain during pregnancy. Method: SHRSP were treated with etanercept (0.8 mg/kg) or vehicle at gestational day (GD) 0, 6, 12 and 18. Animals were sacrificed at GD18. Results: Etanercept reduced systolic blood pressure in the SHRSP after GD12 (ΔSBP GD 10-21 SHRSP 12.0 ± 4.17 vs. ETN 25.8 ± 4.27 mmHg; p&lt;0.05). Uterine arteries from GD18 showed that etanercept reduced uterine artery contraction (SHRSP 57.3 ± 8.75 vs. ETN 35.2 ± 2.19 kPa; p&lt;0.01) and increased carbachol response (SHRSP 13.8 ± 3.8 vs. ETN 40.1 ± 3.25 %; p&lt;0.05). Uteroplacental blood flow analysed using Doppler showed that etanercept reduced uterine artery resistance index in SHRSP (SHRSP 0.79 ± 0.02 vs. ETN 0.61 ± 0.02 UARI; p&lt;0.01). Etanercept increased litter size (SHRSP 7.80 ± 0.44 vs. ETN 12.75 ± 0.94 fetuses), reduced resorption frequency (SHRSP 66.7% vs. ETN 25.0% dams with resorption) and decreased glycogen cell loss from the placenta in SHRSP. We sought to identify the source of excess TNFα in the SHRSP. Natural killer (NK) cells (CD3-CD161+) were increased in the SHRSP relative to the WKY in the maternal circulation (WKY 1.5 ± 0.4 vs. SHRSP 6.06 ± 0.28 %; p&lt;0.01) and placenta (WKY 11.6 ± 2.39 vs. SHRSP 659.8 ± 201.2 cells/mg; p&lt;0.01). These NK cells produced excess TNFα in the SHRSP maternal circulation (SHRSP 6.5 ± 0.4 vs. WKY 2.5 ± 0.4 %; p&lt;0.05) and placenta (SHRSP 65.7 ± 4.2 vs. WKY 16.9 ± 1.7 %; p&lt;0.01) relative to the WKY. In the SHRSP placenta, etanercept treatment reduced the number of cytotoxic NK cells (SHRSP 659.8 ± 201.2 vs. ETN 148.0 ± 12.62 cells/mg; p&lt;0.01) by down-regulating CD161 expression associated with a decrease in granzyme B production (CD161+ 71.47 ± 2.1 vs. CD161 Low 14.32 ± 0.77 % granzyme B+; p&lt;0.01). Conclusions: Excess TNFα plays a causative role in adverse pregnancy outcome in the SHRSP. One source of this TNFα is an increase in NK cells during gestation in the SHRSP. Etanercept targets NK cells in the SHRSP placenta and down-regulates cytotoxic granzyme B production.