Superovulation with an anti-inhibin monoclonal antibody improves the reproductive performance of rat strains by increasing the pregnancy rate and the litter size.

Rats are multiparous rodents that have been used extensively in research; however, the low reproductive performance of some rat strains hampers the broader use of rats as a biomedical model. In this study, the possibility of increasing the litter size after natural mating in rats through superovulation using an anti-inhibin monoclonal antibody (AIMA) was examined. In outbred Wistar rats, AIMA increased the number of ovulated oocytes by 1.3-fold. AIMA did not affect fertilization and subsequent embryonic development, resulting in a 1.4-fold increase in litter size and a high pregnancy rate (86%). In contrast, conventional superovulation by eCG/hCG administration decreased the pregnancy rate to 6-40% and did not increase the litter size. In inbred Brown Norway rats, AIMA increased the litter size by 1.2-fold, and the pregnancy rate increased more than twice (86% versus 38% in controls). AIMA also increased the litter size by 1.5-fold in inbred Tokai High Avoiders and Fischer 344 rats. AIMA increased the efficiency of offspring production by 1.5-, 2.7-, 1.4-, and 1.4-fold, respectively, in the four rat strains. Thus, AIMA may consistently improve the reproductive performance through natural mating in rats, which could promote the use of AIMA in biomedical research.

Lycopene improves maternal reproductive performance by modulating milk composition and placental antioxidative and immune status.

Placental health and milk quality are important for maternal reproductive performance during pregnancy and lactation. Lycopene plays an important role in antioxidation, anti-inflammation and regulating lipid metabolism. The goal of the present study was to investigate the effects of dietary lycopene supplementation in the pig model on reproductive performance, placental health and milk composition during maternal gestation and lactation. In the present study, the litter size of live piglets was increased and the litter size of dead piglets was decreased by lycopene supplementation of the diet of sows. The litter weight at birth and weaning were increased in the lycopene group. Through placental proteomics, we enriched differentially expressed proteins (DEPs), gene ontology (GO) terms, and Kyoto encyclopedia of proteins and genomes (KEGG) pathways involved in immunity, anti-inflammation, antioxidants, and lipid metabolism and transport. Furthermore, in terms of placental health, we analyzed the levels of related enzymes, metabolites and mRNA expression in the placenta. Lycopene was shown to reduce mRNA expression and the levels of placental inflammatory factors, increase the content of immunoglobulin, improve the antioxidant capacity, and improve lipid metabolism and lipid transport in the placenta. In terms of sow milk composition, lycopene increased the levels of immunoglobulins in colostrum and lactose in colostrum and milk. Overall, the results of the present study demonstrate that dietary lycopene supplementation of sows during gestation and lactation improves the reproductive performance to a certain extent; this may be due to lycopene improving the placental health and milk composition of sows.

A reproductive and developmental toxicity screening study of 1,3-butadiene in Sprague-Dawley rats.

1,3 Butadiene (BD) is an industrial intermediate used primarily in product manufacturing with the greatest exposure potential via inhalation. BD was evaluated for reproductive and developmental effects in a Good Laboratory Practice (GLP)-compliant, extended OECD 421 guideline study (completed 2003). Twelve-week old rats (12/sex/dose) were exposed via whole-body inhalation to BD vapor (0, 300, 1500, 6000 ppm) for 6 h/day, 7 days/week, starting 14 days prior to mating through the day prior to euthanasia (total exposures: 83-84 days for F0 males 60-70 days for F0 females). Select F1 offspring (1/sex/litter) were dosed 7 days (postnatal days 21-27 or 28-34), then necropsied. At 1500 and 6000 ppm, treatment-related facial soiling was seen in F0 males and females with decreased body weights/gains in F0 males. F1 males and females exhibited similar effects at 1500 and 6000 ppm. Importantly, the F0 generation had no evidence of altered sperm production, testicular effects, or ovarian atrophy, which were sensitive responses in mice. The no-observed-adverse-effect-level (NOAEL) is 300 ppm due to decreased body weight/gain and facial soiling at 1500 ppm, whereas 6000 ppm serves as a NOAEL for reproductive and developmental endpoints. This study contributes to the weight-of-evidence of differential BD reproductive toxicity in rats and mice.

Oxytocin increases pregnancy rates after fixed time artificial insemination in Kazak ewes.

It is probable that reduced pregnancy rates in ewes after fixed time artificial insemination (FTAI) is attributable, in part, to the reduced number of normal spermatozoa that colonize the oviduct. Administration of oxytocin stimulates both cervical dilation and uterine/oviductal contractility. The hypothesis that oxytocin can enhance sperm transport into the uteri and the oviducts, and thereby increase pregnancy rates, was tested in the present study. Oestrus was synchronized in 199 multiparous Kazak ewes using intravaginal flurogestone-impregnated sponge. The sponge was left in the vagina for 12 days followed with an injection of 330 IU of eCG at sponge removal. Each ewe was intracervically inseminated twice at 50 hr and 62 hr after the removal of sponges using an insemination catheter containing 0.25 ml of diluted semen. Semen was collected from seven Texel rams and all the ejaculates were pooled and diluted in ultra-high temperature-treated commercial skimmed milk without (Control group, 0.05 ml of saline per mL milk, n = 144) or with oxytocin supplement (Oxytocin group, 0.5 U of oxytocin per ml milk, n = 55). Pregnancy status was determined by transabdominal ultrasound examination 45 days after insemination. Lambing performance was recorded at delivery. Significant differences were observed between the Oxytocin group and the Control group in terms of the pregnancy rate and the fecundity rate (85.5% and 92.7% versus 68.8% and 72.9%, respectively). In conclusion, low dose oxytocin supplementation of semen extender significantly increased pregnancy and fecundity rates in oestrus-synchronized Kazak ewes after FTAI.

Oral deoxynivalenol toxicity in Harlan Sprague Dawley (Hsd:Sprague Dawley® SD®) rat dams and their offspring.

There is widespread human exposure to deoxynivalenol (DON), a fungal mycotoxin found globally in many grain-based foods and animal feed. Acute exposures to high levels of DON are associated with gastrointestinal effects and emesis in humans and some animals, but the effects of low-dose exposures throughout the lifetime, a more likely exposure scenario in humans, are understudied. Therefore, this study was designed to identify doses of DON that could be used to evaluate long-term toxicity following perinatal exposure. Time-mated Harlan Sprague Dawley (Hsd:Sprague Dawley® SD®) rats were administered 0, 0.03, 0.1, 0.3, 1, or 3 mg/kg/day of DON once daily via gavage starting on gestational day 6 through postnatal day (PND) 27. F1 animals were administered the same dose as their respective dams via gavage starting on PND 12 until PND 27. Animals were euthanized on PND 28. DON had no effect on maternal body weight or feed consumption at any dose. Findings were limited to the 3 mg/kg/day group: F0 females had smaller live litter sizes than controls and F1 pups had lower body weight (4-13%) compared to controls. By PND 28, F1 body weight, after adjustments for litter effects, was 10-13% lower than controls. Blood samples obtained on PND 28 showed no increases in frequencies of micronucleated immature erythrocytes in either F0 or F1 animals. In summary, doses of DON up to 3 mg/kg/day did not affect maternal survival or body weight. Doses of 3 mg/kg/day resulted in slight toxicity manifested as decreased body weight in the offspring. The no-observed effect level was 1 mg/kg/day.

Combined vapor exposure to THC and alcohol in pregnant rats: Maternal outcomes and pharmacokinetic effects.

Cannabis is the most frequently used illicit drug among pregnant women, yet the potential consequences of prenatal cannabis exposure on development are not well understood. Electronic cigarettes have become an increasingly popular route of administration among pregnant women, in part to user's perception that e-cigarettes are a safer route for consuming cannabis products. Importantly, half of pregnant women who consume cannabis also report consuming alcohol, but research investigating co-consumption of these drugs is limited, particularly with current routes of administration. The purpose of this study was to establish a co-exposure vapor inhalation model of alcohol and THC in pregnant rats, to ultimately determine the effects on fetal development. Pregnant Sprague-Dawley rats were exposed to moderate doses of THC via e-cigarettes, alcohol, the combination, or vehicle daily from gestational days 5-20. Importantly, pharmacokinetic interactions of alcohol and THC were observed during pregnancy. Combined exposure consistently increased blood alcohol concentrations, indicating that THC alters alcohol metabolism. In addition, THC levels also increased over the course of pregnancy and THC metabolism was altered by alcohol. Alcohol, but not THC, exposure during pregnancy reduced maternal weight gain, despite no group differences in food intake. Neither prenatal alcohol nor THC exposure altered gestational length, litter size, sex ratio or birth weight. However, prenatal alcohol exposure delayed eye opening, and prenatal THC exposure decreased body weights during adolescence among offspring. These individual and synergistic effects suggest that this novel co-exposure vapor inhalation paradigm can effectively be used to expose pregnant dams, exerting some effects on fetal development, while avoiding nutritional confounds, birth complications, or changes in litter size. With this model, we have demonstrated that combining THC and alcohol alters drug metabolism, which could have important consequences on prenatal development.

Effects of dietary inulin during late gestation on sow physiology, farrowing duration and piglet performance.

In this study there was evaluation of effects of dietary inulin during late gestation on sow physiology, farrowing duration and piglet performance. At day 80 of gestation sows were randomly assigned to four groups：basal diet (CON); or basal diet with 0.8 %; 1.6 %; or 2.4 % inulin. The feeding of the diet with 1.6 % inulin resulted in larger weights of the litter at birth a shorter duration of the farrowing period, lesser average birth interval between piglets, lesser number of piglets dead at birth, and fewer piglets/sow dead at birth (P < 0.05). When sows were fed 0.8 % and 1.6 % IN, there was a larger litter weight at weaning, sow average daily feed intake and piglet average daily gain during lactation compared with values for these variables in the CON group (P <  0.05). Additionally, there was an increase in serum concentration of free fatty acid, total cholesterol, and high-density lipoprotein cholesterol with increasing amounts of inulin in the diet (linear, P <  0.05). Sows fed 1.6 % IN had greater serum concentrations of glucose than those in the CON group (P <  0.05). Furthermore, there was a linear increase in serum activity of total antioxidant capacity, total superoxide dismutase and glutathione peroxidase with increasing amounts of inulin in the diet (P <  0.05). In conclusion, results of the present study indicated feeding inulin during late gestation improved reproductive performance of sows, thus, may be a novel additive for the pig industry in improving efficiency of pork production.

Supplemental effects of dietary lysophospholipids in lactation diets on sow performance, milk composition, gut health, and gut-associated microbiome of offspring.

Dietary lysophospholipids (LPL) would influence milk composition of sows, thus positively affect intestinal health of offspring. The objective of this study was to determine effects of dietary LPL fed to lactating sows on performance, milk characteristics, gut health, and gut-associated microbiome of offspring. Sixty pregnant sows were allotted to 2 treatments in a randomized complete block design with parity and BW as blocks on day 110 of gestation. Treatments were CON (no added LPL) and LPL (0.05% LPL; Lipidol-Ultra, Pathway Intermediates, Shrewsbury, UK). Sows were fed 2 kg/d from day 110 of gestation until farrowing and ad libitum after farrowing. Diets were formulated to meet NRC requirement for lactating sows. Colostrum and milk samples from 12 sows per treatment were collected to measure nutrients and immunoglobulins on days 1 and 18 of lactation, respectively. Twelve piglets per treatment (1 piglet per litter) were euthanized on day 18 to collect tissues to measure tumor necrosis factor-α, interleukin-8 (IL-8), malondialdehyde, protein carbonyl, IgA, histomorphology, crypt cell proliferation rate, and microbiota in the jejunum and colon. Data were analyzed using the MIXED procedure of SAS, and the mortality was analyzed using the GLIMMIX procedure of SAS. There was no difference in sow BW, parity, and litter size between treatments on day 0 of lactation. Sows fed LPL had increased (P < 0.05) litter BW gain (53.9 vs. 59.4 kg) and decreased piglet mortality (13.9% vs. 10.6%) on day 18 of lactation. Sows fed LPL had increased (P < 0.05) omega-6:omega-3 (22.1 vs. 23.7) and unsaturated:saturated (1.4 vs. 1.6) fatty acids ratios with increased oleic acid (29.1% vs. 31.4%) and tended to have increased (P = 0.092) IgG (1.14 vs. 1.94 g/L) and linoleic acid (17.7% vs. 18.7%) in the milk on day 18 of lactation. Piglets from sows fed LPL had increased (P < 0.05) IL-8 (184 vs. 245 pg/mg) and crypt cell proliferation rate (39.4% vs. 40.9%) and tended to have increased (P = 0.095) Firmicutes:Bacteroidetes ratio (1.0 vs. 3.5) in the jejunum. In conclusion, sows fed with LPL had milk with increased IgG, oleic acids, and linoleic acids without changes in BW and backfat during lactation. These changes could contribute to improved survivability and intestinal health of piglets by increasing IL-8 concentration, enhancing balance among gut-associated microbiome, and increasing enterocyte proliferation in the jejunum.

Un-riped fruit pods of Prosopis cineraria (L.) Druce ameliorates Cisplatin therapy-induced partial testicular atrophy in male Wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Prosopis cineraria (L.) Druce is a plant that is widely found in dry parts of India. The unripe fruit pod has a very specific traditional claim of treating male infertility and increasing sperm volume and count. AIM: The present work was endeavored to investigate the long-standing traditional claim of P. cineraria on meliorating male fertility. The study focussed on cancer therapy-induced male infertility and curative effect of the extract with an appraisal on any possible revitalizing effects on sperm count, morphology, motility, and viability combined with hormonal and histopathological investigations. MATERIALS AND METHODS: Male Wistar rats were used for the study. Two different doses of 400 mg/kg/d and 800 mg/kg/d (both p.o.) of the Hydroalcoholic extract were chosen as test dose while Clomiphene (25 mg/kg/d; p.o.) treatment served as standard treatment. Animals were initially injected with cisplatin (1 mg/kg/d; i.p.) for 15 days and the drug treatment was begun at the 16th day and continued till 43rd day (28 days treatment). Later all male animals got cohabited with female animals in the ratio 1:3. On confirmation of mating, female animals were isolated. Male animals were euthanized on batches. Testis and epididymis were weighed and homogenized. Sperm count, motility, morphology, viability, and headcount. The serum collected was evaluated for serum FSH, LH, and testosterone levels. On day Gestational day 15, gravid uterus observations were calculated to evaluate male and female fertility parameters. RESULTS: There were statistically significant improvements (p < 0.001) in sperm motility, sperm count, sperm viability, and improved morphological features. The same pace was also noticed in testosterone, FSH and LH levels in serum and LPO, CAT, GSH, GPx and SOD in testicular tissues. The extract treated male animals produced better and healthy litter compared to cisplatin-treated animals with less pre- and post-implantation loss. CONCLUSION: Consolidating the results seen, the extract ameliorated the testicular toxicity caused by cisplatin in a dose-dependent manner. Further insight and evaluation of the phytochemicals of the pods should be performed to bring up commercial viability.

Triclosan treatment to pregnant albino rats affects offspring numbers and the liver of both the pregnant rats and their offspring, and these effects are ameliorated by co-treatment with bee honey.

We have assessed the effects of the broad-spectrum bactericide triclosan on the liver of pregnant albino rats and their offspring, and evaluated the protective potential of bee honey, which has radical-scavenging properties. The study involved treatment of 72 pregnant rats followed by examination of the pregnant rats and their offspring. The pregnant rats were divided equally into six groups (I-VI), each of which was subdivided equally into two Subgroups (A and B). Rats in the A subgroups were gavaged with a daily dose of 1.26 ml distilled water (IA), 1 ml corn oil (IIA), 1.68 ml aqueous solution of Clover Blossom honey (IIIA), 0.3 mg triclosan (IVA), 13 mg triclosan (VA), or 1.68 ml aqueous solution of honey with 13 mg triclosan (VIA), throughout pregnancy. Rats in the B subgroups received the same treatments throughout pregnancy and for 14 days after delivery. At the end of the experiments, the offspring's numbers were recorded and blood samples were taken from the pregnant rats for analysis. The livers of the studied groups were subjected for; histological study, morphometric analysis, and biochemical estimation of markers of oxidative stress. The results showed that the acceptable daily intake of triclosan did not induce significant pathological changes in the liver while high dose of triclosan induced pathological changes in the livers and reduced the numbers of offspring. Co-administration of honey with triclosan ameliorated most pathological change. Therefore, decrease the exposure of the pregnant women to triclosan is encouraged or co-supplementation with bee honey if exposure could not be avoided.

Effects of chlorocholine chloride on pubertal development and reproductive functions in male rats.

Chlorocholine chloride (CCC), a plant growth retardant, may act as an endocrine disruptor. Our previous study showed that pubertal CCC exposure in rats might decrease testosterone (T) synthesis. This study observed the changes in pubertal development and reproduction of male rats exposed to CCC and its underlying mechanisms. Rats were exposed to CCC (0, 75, 137.5 and 200 mg/kg bw/day) from postnatal day 23 to 60. The results showed that CCC treatment delayed the onset of puberty and reduced the relative organ weight of prostate. Seminiferous tubules with deciduous spermatogenic cells were observed in the 200 mg/kg bw/day group. Sexual behavior was inhibited in the 137.5 and 200 mg/kg bw/day groups. Sperm motility, litter size and normalized anogenital distance (AGD) of male pups were decreased in the 137.5 and 200 mg/kg bw/day groups. Serum kisspeptin level and serum and testicular levels of T were reduced in all CCC treated groups. Crucial hormones in hypothalamic-pituitary-testicular (HPT) axis were reduced subsequently after CCC treatment. Collectively, our results demonstrated that CCC might disturb HPT axis through suppressing the secretion of kisspeptin and subsequently lead to delayed puberty onset and impaired reproductive functions.

Combined effects of maternal exposure to fungicides on behavioral development in F1 -generation mice: 1. Several dose study of both imazalil and thiabendazole.

BACKGROUND: Few published studies are reported for neurobehavioral toxicity of combined exposure to fungicides in mammals. This study was aimed to evaluate reproductive and neurobehavioral effects of maternal exposure to combined fungicides in mice. METHODS: Imazalil (IMZ) and thiabendazole (TBZ) were given in the diet to provide levels of 0/0% (control), 0.0015/0.006% (IMZ/TBZ), 0.006/0.018%, and 0.024/0.054% during the gestation and lactation periods. Selected reproductive and neurobehavioral parameters were measured in the F1 generation. RESULTS: No adverse effect of IMZ/TBZ was observed in litter size, litter weight, or sex ratio at birth. The average body weight of male and female offspring was increased significantly in treatment groups during the lactation period. With respect to behavioral developmental parameters, the swimming head angle on PND 7 of male offspring was significantly accelerated in the treatment groups. After weaning, the movement time of exploratory behavior shortened in a significant dose-related manner in adult males of the F1 generation. In adult females, the rearing time of exploratory behavior lengthened in a significant dose-related manner in the F1 generation. Spontaneous behavior examination indicated that longitudinal patterns of each of the total distance and number of rearing were different during the control and treatment groups in the F1 -generation females. Parallel width of the control and treatment groups was significantly different in the average time of movement and rearing in the F1 -generation females. CONCLUSIONS: The high-dose level of IMZ/TBZ in the present study produced several adverse effects in neurobehavioral parameters after weaning without concurrent chemical administration in mice.

Lead-mediated inhibition of lysine acetylation and succinylation causes reproductive injury of the mouse testis during development.

Lead (Pb), a widespread heavy metal, may induce serious diseases, particularly male reproductive injury. However, the mechanisms by which Pb induces testicular injury remain unclear. In this paper, we established a mouse model of Pb-induced testicular injury via an intraperitoneal injection of lead chloride at a concentration of 1.5 mg/kg body weight. We confirmed that Pb could induce a series of injuries, including a low litter size, smaller testes, more weak offspring, direct injury, and aberrant spermiogenesis. Our study demonstrated that Pb could inhibit lysine acetylation (Kac) and succinylation (Ksuc) via western blot (WB) and immunofluorescence (IF) analyses. We subsequently separated different germ cells that contained Pre-meiotic spermatogonia (SPG), meiotic spermatocyte (SPC), and round spermatid (RS) into the Pb-treated and control groups and verified that Pb inhibited Kac in SPC, RS, and particularly, during meiosis. Furthermore, our results regarding the inhibition of pyruvate kinase and mitochondrial electron transport chain complex I and II in the Pb-treated groups suggested that Pb may restrain key enzymes to block the TCA cycle and that the low TCA cycle activity could reduce the contents of two important metabolites, acetyl-CoA and succinyl-CoA, to inhibit Kac and Ksuc. Moreover, we examined the influences of the inhibition of Kac and Ksuc on spermiogenesis, which indicated that decreased Kac and Ksuc could impede the replacement of transition proteins in elongating sperm and disorder the distribution of germ cells in the seminiferous tubule. Our research provides novel insights into the mechanisms of Pb reproductive toxicity with respect to lysine acetylation and succinylation.

Effects of feeding melatonin during proestrus and early gestation to gilts and parity 1 sows to minimize effects of seasonal infertility1.

This study tested whether supplemental melatonin given to mimic the extended nighttime melatonin pattern observed in the higher fertility winter season could minimize infertility during summer and fall in swine. Exogenous melatonin was fed during periods coinciding with follicle selection, corpus luteum formation, pregnancy recognition, and early embryo survival. Experiments were conducted at a commercial farm in 12 sequential replicates. In Exp. 1a, mature gilts (n = 420) that had expressed a second estrus were assigned by weight to receive once daily oral Melatonin (MEL, 3 mg) or Control (CON, placebo) at 1400 h for 3 wk starting before insemination at third estrus. In Exp. 1b, parity 1 sows (n = 470) were randomly assigned by lactation length to receive MEL or CON for 3 wk, starting 2 d before weaning. Follicles, estrus, pregnancy, and farrowing data were analyzed for the main effects of treatment, season (4-wk periods), and their interaction. Environmental measures were also analyzed for reproductive responses. In Exp. 1a, there was no effect (P > 0.10) of MEL on age at third estrus (203 d), follicle size after 7 d of treatment (5.0 mm), estrous cycle length (22.6 d), return to service (9.2%), farrowing rate (FR, 80.0%), or total born pigs (TB, 13.6). However, there was an effect of season (P = 0.03) on number of follicles and on gilts expressing estrus within 23 d of the previous estrus (P < 0.005). In Exp. 1b, there was no effect of MEL (P > 0.10) on follicle measures, wean to estrous interval, FR (84.0%), or TB (13.0). But MEL (73.5%) reduced (P = 0.03) estrous expression within 7 d of weaning compared with CON (82.0%) and season (P = 0.001) decreased FR by ~14.0% during mid summer. Also, gilts and parity 1 sows exposed to low light intensity (<45 lx) during breeding had reduced conception (-8%) and farrowing (-15%) rates, compared with higher light intensity. Similarly, high temperatures (>25 °C) during breeding also reduced gilt conception rates by 7%. Although there was clear evidence of seasonal fertility failures in gilts and sows, MEL treatment did not improve fertility in gilts and reduced estrus in parity 1 sows. It is possible that differences in lighting and thermal environments before breeding could explain the differential response to MEL in sows and gilts.

Implantation and pregnancy outcome of Sprague-Dawley rats exposed to pirimiphos-methyl.

OBJECTIVE: This study was designed to investigate the effect of sublethal doses (10, 60, and 120 mg/kg of pirimiphos-methyl on implantation and pregnancy in female Sprague-Dawley rats. Pirimiphos-methyl is a pesticide widely used worldwide, especially in Africa to protect food against pests and has gained widespread acceptance. METHODS: Pregnant Sprague-Dawley rats used for this study had access to food and water ad libitum and were divided into a control group and three experimental groups based on dose of chemical given. The pregnant rats were given pirimiphos-methyl orally on days 1-5, 1-7, 7-18th day of gestation and from day 1 to term. Implantation studies were carried out on days 6 and 8 of pregnancy, while the fetal parameters were ascertained on day 19 of pregnancy and at term. Serum levels of progesterone and estradiol were measured on days 6, 8 and 19 of pregnancy. RESULTS: Sublethal administration of pirimiphos-methyl showed decreased number of implantation sites on days 6 and 8, fetal weight, crown-to-rump length, length of umbilical cord and placenta weight (day 19), birth weight, litter size and total number (at term) in rats administered with pirimiphos-methyl when compared with control. CONCLUSION: Administration of pirimiphos-methyl resulted in a reduced implantation rate due to decreased uterine receptivity caused by an imbalance in the level of estradiol and progesterone and impaired reproductive outcome during pregnancy.

Effect of expression alteration in flanking genes on phenotypes of St8sia2-deficient mice.

ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 (ST8SIA2) synthesizes polysialic acid (PSA), which is essential for brain development. Although previous studies reported that St8sia2-deficient mice that have a mixed 129 and C57BL/6 (B6) genetic background showed mild and variable phenotypes, the reasons for this remain unknown. We hypothesized that this phenotypic difference is caused by diversity in the expression or function of flanking genes of St8sia2. A genomic polymorphism and gene expression analysis in the flanking region revealed reduced expression of insulin-like growth factor 1 receptor (Igf1r) on the B6 background than on that of the 129 strain. This observation, along with the finding that administration of an IGF1R agonist during pregnancy increased litter size, suggests that the decreased expression of Igf1r associated with ST8SIA2 deficiency caused lethality. This study demonstrates the importance of gene expression level in the flanking regions of a targeted null allele having an effect on phenotype.

Dietary supplementation with garcinol during late gestation and lactation facilitates acid-base balance and improves the performance of sows and newborn piglets1.

The present study was conducted to evaluate the effects of dietary garcinol supplementation during late gestation (from the 90th day of pregnancy; day 90) and lactation on the acid-base balance of the umbilical cord blood and performance of sows and piglets. Sixty sows (Duroc × Yorkshire × Landrace; second- or third-parity; n = 20) were randomly divided into 3 gestation (day 90 of pregnancy) or lactation treatments, control diet (CON; basal diet), basal diet with 200 mg garcinol, and basal diet with 600 mg garcinol per kg of feed. The body weight (BW); backfat thickness and litter size of the sows; and birth weight, weaning weight, and mortality of piglets were recorded. Sows' blood and piglets' umbilical cord blood were collected for the measurements of hematological parameters and antioxidative and immune indexes, and acid-base balance parameters, respectively. The colostrum and milk and fecal samples of the sows were also collected for analysis of milk composition and apparent total tract nutrient digestibility. Garcinol had no effect on the BW and backfat thickness of the sows but significantly increased the birth weight and weaning weight of piglets (P < 0.05) and decreased the mortality (P < 0.05). Moreover, the white blood cell counts and neutrophil count, mean cell hemoglobin, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activity in the plasma of the sows were increased more significantly (P < 0.05) in the garcinol groups than that in the CON group, whereas the malondialdehyde (MDA) content was decreased (P < 0.05). The garcinol treatment significantly increased the pH, HCO3- and base excess values (P < 0.05), whereas it decreased the pCO2 and lactate content (P < 0.05) in the umbilical blood. Dry matter (DM), ash, and ether extract in the colostrum were similar between groups (P > 0.05), whereas the garcinol significantly increased the crude protein (CP) in the milk. In addition, the content of immunoglobulin A (IgA) and immunoglobulin G (IgG) in the plasma of piglets and in colostrum and milk of sows were increased more significantly (P < 0.05) in the garcinol groups than that in the CON group. The apparent total tract nutrient digestibility was similar between treatments. Collectively, this study indicates that sows fed with garcinol in late gestation and lactation showed improved maternal health and antioxidative status, milk protein content, acid-base balance in the umbilical cord blood, and growth performance in piglets, showing promise in natural plant extract nutrition for sows.

Optimal lysine in diets for high-yielding lactating sows1.

The objective of the current study was to determine the optimal concentration of dietary standardized ileal digestible (SID) Lys required to maximize litter gain and minimize sow BW loss in modern high-yielding lactating sows when SID CP was kept constant across dietary treatments. A total of 396 parity 1 to 5 sows (L × Y, DanBred, Herlev, Denmark) were included in the study from day 3 after farrowing until weaning at day 26. Sows were allocated to 6 dietary treatments increasing in SID Lys concentration (6.19, 6.90, 7.63, 8.33, 9.04, and 9.76 g/kg). Diets were isoenergetic (14.04 MJ ME/kg as-fed). Litters were standardized to 14 piglets at day 3 ± 2 d postpartum. At day 3 ± 2 d and at day 26 ± 3 d in lactation, litter weight, and sow BW and back fat were registered. On a subsample of 72 parity 2 to 4 sows, litters were additionally weighed at days 10 and 17 ± 3 d, and milk and blood were sampled at day 3 ± 2 d, and 10, 17 and at 24 ± 3 d in lactation. For the 72 sows, body pools of fat and protein were also determined at days 3 ± 2 and 26 ± 3 d using the D2O dilution technique. All data were analyzed as a randomized complete block design using PROC MIXED in SAS. Furthermore, data were subjected to linear and quadratic polynomial contrasts. Variables with quadratic or linear effects or days in milk × treatment interactions were selected for analysis in PROC NLMIXED using linear broken-line models to evaluate optimal SID Lys concentrations. Only models that converged and the best fitting models were included. Average daily litter gain increased until a breakpoint at 8.11 g/kg of SID Lys (as-fed). At and above the breakpoint, multiparous and primiparous sows had litter gains of 3.36 and 2.93 kg/d, respectively. Weaning litter size (13.0 ± 0.1) was similar between the 6 dietary treatments (P = 0.28). Lactation sow BW loss was minimized to 0.17 kg/d at 9.05 g/kg of SID Lys and sow body protein loss was minimized to 0.23 kg at 9.22 g/kg of SID Lys. Linear broken-line analyses showed that for 3, 10, 17, and 24 DIM, plasma urea was minimized at 7.02, 8.10, 8.73, and 8.32 g/kg of SID Lys, respectively, and milk fat was maximized at 7.80 g/kg of SID Lys. In conclusion, in our conditions, high-yielding lactating sows required 8.11 g/kg of SID Lys to maximize litter gain and 9.05 g/kg of SID Lys to minimize sow BW loss. Based on plasma urea, the optimal dietary concentration of SID Lys was lowest in week 1, intermediate in week 2 and 4, and greatest in week 3 of lactation.

Derivation of a chronic reference dose for perfluorohexane sulfonate (PFHxS) for reproductive toxicity in mice.

Perfluorohexane sulfonate (PFHxS) is a six-carbon perfluoroalkyl sulfonic acid that was used as an industrial surfactant, but is now found as an environmental contaminant worldwide. In addition to its use as an industrial surfactant, it is a legacy contaminant from the use of aqueous film-forming foams. Despite its widespread occurrence in the environment and evidence of biological activity associated with PFHxS and similar perfluoroalkyl sulfonic acids in rodents, there is no oral toxicity value currently available from the IRIS Database. To derive an oral reference dose (RfD) for PFHxS, available toxicity studies were reviewed using a weight-of-evidence approach. A 42-day mouse reproductive study was chosen as the critical study for the derivation of the oral RfD. Benchmark dose modeling was utilized to derive a point of departure (POD) for a reduction in litter size. A 95% lower confidence limit on the benchmark dose (BMDL) of 13,900 ng/mL (serum PFHxS) was modeled for a reduction in litter size. An oral RfD for PFHxS of 4.0 ng/kg/d was calculated by conversion of the BMDL to a human equivalent oral dose using a human half-life adjusted dosimetric conversion factor and the application of a total uncertainty factor of 300. Additional research is needed to better characterize the toxicity associated with oral exposure to PFHxS and refine the development of toxicity values.

Dietary L-arginine supplementation during early gestation of gilts affects conceptuses development.

l-arginine supplementation of sows has led to improvement of reproductive performance, but the mechanisms responsible for the positive effects of arginine during gestation on conceptuses survival and development are still poorly understood. Thus, we aimed to evaluate effects of 1.0% l-arginine supplementation (ARG) on phenotypic traits of commercial gilts, embryos and fetuses, concentration of gilts' blood metabolites, expression of developmental and cellular apoptosis genes in conceptuses of 25 and 35 days. At 25 days, IGF1 gene was more expressed in embryos from ARG than in embryos from control gilts (CON) (P = 0.05). At this same gestational age, ARG embryos tended to be heavier compared to CON (P = 0.07) and ARG gilts showed a trend to have a greater arginine concentration in blood plasma (P = 0.06). However, at 35 days of gestation, arginine concentration in blood plasma of ARG gilts tended to be lower compared to CON (P = 0.06) and ARG fetuses showed smaller cephalic-caudal length (P = 0.05). These results indicate that duration of supplementation is determinant for arginine effects, not only on the females performance but also on the conceptuses, since supplementation upregulated IGF1 expression at 25 days, in addition to the reduction of cephalic-caudal length of 35-day fetuses.