Offspring born to ewes fed high salt during pregnancy have altered responses to oral salt loads

Prenatal growth is sensitive to the direct and indirect effects of maternal dietary intake; manipulation can lead to behavioural and physiological changes of the offspring later in life. Here, we report on three aspects of how a high-salt diet during pregnancy (conception to parturition) may affect the offspring's response to high oral salt loads: (i) dietary preferences for salt; (ii) response to salt and water balance and aldosterone and arginine vasopressin (AVP) concentrations after an oral salt challenge; (iii) concentrations of insulin and leptin after an oral salt challenge. We used two groups of lambs born to ewes fed either a high-salt (13% NaCl) diet during pregnancy (S lambs; n = 12) or control animals born to ewes fed a conventional (0.5% NaCl) diet during pregnancy (C lambs; n = 12). Lambs were subjected to short- (5 min) and long-term (24 h) preference tests for a high-salt (13% NaCl) or control diet, and the response to an oral challenge with either water or 25% NaCl solution were also carried out. Weaned lambs born to ewes fed high salt during pregnancy did not differ in their preference for dietary salt, but they did differ in their physiological responses to an oral salt challenge. Results indicate that these differences reflect an alteration in the regulation of water and salt balance as the metabolic hormones, insulin and leptin, were not affected. During the first 2 h after a single salt dose, S lambs had a 25% lower water intake compared to the C lambs. S lambs had, on average, a 13% lower AVP concentration than the C lambs (P = 0.014). The plasma concentration of aldosterone was higher in the S lambs than in the C lambs (P = 0.013). Results suggest that lambs born to ewes that ingest high amounts of salt during pregnancy are programmed to have an altered thirst threshold, and blunted response in aldosterone to oral salt loads.     

Reproductive capacity of Merino ewes fed a high-salt diet

An option to increase the productivity of saline land is to graze sheep on salt-tolerant plants, which, during the summer/autumn period, can contain 20% to 25% of their dry matter as salt. This study assessed the impact of coping with high dietary salt loads on the reproductive performance of grazing ewes. From the time of artificial insemination until parturition, 2-year-old maiden Merino ewes were fed either a high-salt diet (NaCl 13% of dry matter) or control diet (NaCl 0.5% of dry matter). Pregnancy rates, lamb birth weights, milk composition and the plasma concentrations of hormones related to salt and water balance, and energy metabolism were measured. Leptin and insulin concentrations were lower (1.4 ± 0.09 v. 1.5 ± 0.12 ng/ml; (P < 0.05) and 7.2 ± 0.55 v. 8.2 ± 0.83 ng/ml; P < 0.02) in response to high-salt ingestion as was aldosterone concentration (27 ± 2.7 v. 49 ± 5.4 pg/ml; P < 0.05), presumably to achieve salt and water homeostasis. Arginine vasopressin concentration was not significantly affected by the diets, but plasma concentration of T3 differed during gestation (P < 0.02), resulting in lower concentrations in the high-salt group in the first third of gestation (1.2 ± 0.18 v. 1.3 ± 0.14 pmol/ml) and higher concentrations in the final third of gestation (0.8 ± 0.16 v. 0.6 ± 0.06 pmol/ml). T4 concentration was lower in ewes ingesting high salt for the first two-thirds of pregnancy (162 ± 8.6 v. 212 ± 13 ng/ml; P < 0.001). No substantial effects of high salt ingestion on pregnancy rates, lamb birth weights or milk composition were detected.     

Nutritional status of adult ewes during early and mid-pregnancy. 1. Effects of plane of nutrition on ewe reproduction and offspring performance to weaning

The objective of this study was to determine the effects of plane of nutrition during early and mid-pregnancy on the performance of mature ewes and their offspring. From day 0 to day 39 post mating (early pregnancy, EP), 82 multiparous ewes were fed to provide either 60% (low, L), 100% (medium, M) or 200% (high, H) of predicted metabolisable energy (ME) requirements for maintenance, following a synchronised mating. From day 40 to day 90 (mid-pregnancy, MP), ewes were provided with either 80% (M) or 140% (H) of ME requirements. After 90 days of gestation, all ewes were fed to meet requirements for late pregnancy. During EP, mean live weight (LW) and body condition score (BCS) change of ewes were -6.3, -0.8 and +6.0 kg and -0.02, +0.10 and +0.22 units in the L-, M- and H-EP treatments, respectively. During MP, mean LW and BCS change were -0.8 and +4.9 kg and -0.09 and +0.09 units in the M- and H-MP treatments, respectively (P < 0.001). Treatments had no effect (P > 0.05) on conception rate, although there tended to be an inverse relationship (P = 0.085) between plane of nutrition in EP and plasma progesterone concentrations at day 42 of gestation. EP nutrition influenced foetal development with lambs from ewes offered diet L-EP being smaller (P < 0.01) at day 56 than M- or H-EP lambs. However, at parturition L-EP lambs were heavier (P < 0.05) and tended to have higher (P = 0.056) immunoglobulin status 24 h after birth. Mortality rates at weaning were reduced (P < 0.05) for lambs born from ewes offered diet L-EP compared with M- or H-EP lambs. Diet M during mid-pregnancy resulted in larger (P < 0.05) foetuses at day 80 of gestation. At parturition, these lambs had longer head and crown-rump lengths than H-MP lambs (P < 0.05). Lambs born to ewes offered diet M-MP tended to progress faster to attempting to suckle than H-MP lambs (P = 0.089). There was an interaction between plane of nutrition in early and mid-pregnancy, whereby the highest number of lambs weaned was a result of diet L-EP followed by diet M-MP. These results indicate that in adult ewes, temporary nutrient restriction during early pregnancy results in better lamb survival; and mild nutrient restriction in mid-pregnancy tends to improve neonatal behaviour and results in lambs with longer skeletal size.     

Effect of dam weight and pregnancy nutrition on average lactation performance of ewe offspring over 5 years

The foetal mammary gland is sensitive to maternal weight and nutrition during gestation, which could affect offspring milk production. It has previously been shown that ewes born to dams offered maintenance nutrition during pregnancy (day 21 to 140 of gestation) produced greater milk, lactose and CP yields in their first lactation when compared with ewes born to dams offered ad libitum nutrition. In addition, ewes born to heavier dams produced greater milk and lactose yields when compared with ewes born to lighter dams. The objective of this study was to analyse and compare the 5-year lactation performance of the previously mentioned ewes, born to heavy or light dams that were offered maintenance or ad libitum pregnancy nutrition. Ewes were milked once per week, for the first 6 weeks of their lactation, for 5 years. Using milk yield and composition data, accumulated yields were calculated over a 42-day period for each year for milk, milk fat, CP, true protein, casein and lactose using a Legendre orthogonal polynomial model. Over the 5-year period, ewes born to heavy dams produced greater average milk (P=0.04), lactose (P=0.01) and CP (P=0.04) yields than offspring born to light dams. In contrast, over the 5-year period dam nutrition during pregnancy did not affect average (P>0.05) offspring milk yields or composition, but did increase milk and lactose accumulated yield (P=0.03 and 0.01, respectively) in the first lactation. These results indicate that maternal gestational nutrition appears to only affect the first lactational performance of ewe offspring. Neither dam nutrition nor size affected grand-offspring live weight gain to, or live weight at weaning (P>0.05). Combined these data indicate that under the conditions of the present study, manipulating dam weight or nutrition in pregnancy can have some effects of offspring lactational performance, however, these effects are not large enough to alter grand-offspring growth to weaning. Therefore, such manipulations are not a viable management tool for farmers to influence lamb growth to weaning.     

Effect of plane of nutrition of 1- and 2-year-old ewes in early and mid-pregnancy on ewe reproduction and offspring performance up to weaning

The objective of the present study was to determine the effect of plane of nutrition in early pregnancy (EP) and mid-pregnancy (MP), on the productive performance of 1- and 2-year-old ewes and their offspring. Over 2 successive years, between days 0 and 39 after synchronized mating (EP), 1- (n = 117) and 2- (n = 52) year-old ewes were allowed 60% (low, L-EP), 100% (medium, M-EP) or 200% (high, H-EP) of requirements for maintenance (M). Between days 40 and 90 (MP), 1-year-old ewes were allowed 140% (M-MP) or 200% (H-MP), while 2-year-old ewes were allowed 80% (M-MP) or 140% (H-MP) of their M requirement. After day 90, all ewes were fed to meet requirements for late pregnancy. Increasing the plane of nutrition between days 0 and 39 resulted in increases in live weight (LW) (P < 0.001) and body condition score (BCS) (P < 0.001) during the EP period (H-EP > M-EP > L-EP), differences that in 1-year-old ewes were sustained to lambing (P < 0.05). On day 42 of gestation H-EP ewes had lower plasma progesterone concentrations than L-EP or M-EP ewes in 1- (P < 0.01) and 2- (P < 0.001) year olds. This was concomitant with diet H-EP tending to reduce the number of lambs born per ewe in both age groups (P = 0.06 and 0.07, respectively). Foetuses from 1-year-old L-EP ewes had smaller cranial (P < 0.01) and abdominal (P < 0.05) diameters at day 53 of gestation, with H-EP lambs tending to be heaviest at birth (P = 0.07). Similar findings were recorded for 2-year-old ewes. One-year-old ewes offered diet L-EP presented negative maternal behaviours more frequently (P < 0.05), while the incidence of lamb mortality at 6 weeks tended to be greater for L-EP lambs (P = 0.07). In MP, 1-year-old ewes offered diet M-MP were associated with foetuses with bigger abdominal diameters at day 78 (P < 0.05). However, there were no differences in lamb weight or size at term (P > 0.05). These ewes exhibited more positive maternal behaviours (e.g. increased grooming frequency and duration; P < 0.05) than ewes offered diet H-MP, and their offspring were more successful in suckling (P < 0.05). Results suggest that in young ewes, a temporary nutrient restriction in EP resulted in increased prolificacy. However, ewes and their offspring were lighter at birth and ewe maternal behaviour was poorer, resulting in increased lamb mortality. In MP, a medium plane of nutrition offered to 1-year-old ewes led to improved maternal and offspring behaviour.     

Supplementation of grazing beef cows during gestation as a strategy to improve skeletal muscle development of the offspring

The appropriate supply of nutrients in pregnant cows has been associated with the optimal development of foetal tissues, performance of their progeny and their meat quality. The aim of this study was to evaluate supplementation effects of grazing cows in different stages of gestation on skeletal muscle development and performance of the progeny. Thereby, 27 Nellore cows were divided into three groups (n=9 for each group) and their progeny as follows: UNS, unsupplemented during gestation; MID, supplemented from 30 to 180 days of gestation; LATE, supplemented from 181 to 281 days of gestation. The percentage composition of the supplement provided for the matrices was the following: ground corn (26.25%), wheat bran (26.25%) and soya bean meal (47.5%). The supplement was formulated to contain 30% CP. Supplemented matrices received 150 kg of supplement (1 and 1.5 kg/day for cows in the MID and LATE groups, respectively). After birth, a biopsy was performed to obtain samples of skeletal muscle tissue from calves to determine number and size of muscle fibres and for messenger RNA (mRNA) expression analysis. The percentage composition of the supplement provided for the progeny was the following: ground corn grain (30%), wheat bran (30%), soya bean meal (35%) and molasses (5%). The supplement was formulated to contain 25% CP and offered in an amount of 6 g/kg BW. Performance of the progeny was monitored throughout the suckling period. Means were submitted to ANOVA and regression, and UNS, MID and LATE periods of supplementation were compared. Differences were considered at P<0.10. Birth weight, average daily gain and weaning weight of the offspring did not differ among treatments (P>0.10). Similarly, no differences were observed between calves for nutrient intake (P>0.10). However, greater subcutaneous fat thickness (P=0.006) was observed in the calves of LATE group. The ribeye area (P=0.077) was greater in calves born from supplemented compared with UNS cows. The supplementation of pregnant cows did not affect the muscle fibre size of their progeny (P=0.208). On the other hand, calves born from dams supplemented at mid-gestation had greater muscle fibre number (P=0.093) compared with calves from UNS group. Greater mRNA expression of peroxysome proliferator-activated receptor α (P=0.073) and fibroblast growth factor 2 (P=0.003) was observed in the calves born from MID cows. Although strategic supplementation did not affect the BW of offspring, it did cause changes in carcass traits, number of myofibres, and mRNA expression of a muscle hypertrophy and lipid oxidation markers in skeletal muscle of the offspring.     

血管紧张素AT1受体抗体阳性孕鼠后代高盐饮食后血管功能障碍

血管紧张素AT1受体抗体(AT1-Ab)可损伤胎盘发育,进而导致胎儿宫内生长受限(intrauterine growth restriction,IUGR).根据胎儿源性成人疾病学说,IUGR会明显增加成人后患心血管疾病的几率.本研究旨在观察AT1-Ab阳性孕鼠后代生长至成年后血管功能有无异常.24只雌性Wistar大...     

Performance of dairy ewes fed diets with a fibrolytic enzyme product included in the concentrate during the suckling period

Seventy-two multiparous ewes from two dairy breeds (Manchega, n = 36 and Lacaune, n = 36) were used in a replicated 2 × 2 factorial design to evaluate the effects of diet supplementation with an exogenous fibrolytic enzyme product on lactation performance and feed intake during the suckling period (weeks 1 to 4) according to breed. Ewes were blocked in groups of nine and fed ad libitum after lambing a diet based on 70% forage and 30% concentrate to which the enzyme was added after pelleting. Experimental concentrates were: control (without enzyme) and enzyme (fibrolytic enzyme complex, included at 0.47% volume to weight of concentrate). Twenty-four dry and open ewes (Manchega, n = 12 and Lacaune, n = 12) were also grouped by breed and used to measure the fill value of the ration used. During the suckling period, milk yield, milk composition, dry matter intake, lamb growth, as well as body weight change and body condition score change were not affected by enzyme supplementation. Breed effect was significant for milk yield, the Manchega ewes yielding less milk with a higher content of milk components than the Lacaune ewes. The opposite was observed for dry matter intake. Enzyme supplementation reduced intake by 9% in the dry ewes, resulting in a greater fill value of the diet. In conclusion, no lactational effects were detected when the fibrolytic enzyme product was added to the concentrate fed to dairy ewes.     

Maternal backfat depth in gestating sows has a greater influence on offspring growth and carcass lean yield than maternal feed allocation during gestation

A commercial pig spends nearly half of its life in utero and its nutrition during this time can influence birth weight and postnatal growth. We hypothesised that postnatal growth is increased in pigs raised by sows with a high backfat depth and high level of energy intake during gestation compared with sows with a low backfat depth and low level of energy intake during gestation. This was tested in a 2×3 factorial design experiment with 2 factors for gilt backfat depth (Thin and Fat) and 3 factors for gestation feed allowance (Restricted, Control and High). Between d 25 and d 90 of gestation, Thin gilts (n=68; 12±0.6 mm P2 backfat) and Fat gilts (n=72; 19±0.6 mm P2 backfat) were randomly allocated, as individuals, to a gestation diet (6.19 g/kg lysine, 13.0 MJ DE/kg) at the following feed allowances: 1.8 kg/day (Restricted); 2.5 kg/day (Control) and 3.5 kg/day (High). For the remainder of gestation and during lactation all gilts were treated similarly. At weaning (day 28), 155 piglets were sacrificed and 272 were individually housed and followed through to slaughter (day 158). At day 80 of gestation, fasted Thin Restricted gilts had lower serum IGF-1 concentrations than Thin High or Thin Control fed gilts (P<0.001). Pigs born from Fat gilts had greater backfat depths (P<0.05), a lower lean meat yield (P<0.05) and were heavier (P<0.05) at slaughter than pigs born from Thin gilts. Gilt gestation feed allowance had only transitory effects on average daily gain and feed conversion efficiency and had no effect on pig weight at slaughter (P>0.05) or lean meat yield (P>0.05). In conclusion, gilts with a backfat depth of ~19 mm at insemination produced pigs that were heavier and fatter at ~158 days of age than those born from gilts with ~12 mm backfat depth at insemination. Maternal body condition during gestation had a more predominant influence on growth parameters of the offspring, such as weight at slaughter and backfat depth, than did feed level during gestation.     

Effects of late gestation shearing on BW,feed intake and plasma metabolite concentrations in Rambouillet ewes managed outdoors during winter

The majority of lambs in the United States are born from late winter to early spring and pregnant ewes are generally sheared in the last third of pregnancy. Although there are benefits to shearing before parturition, shorn animals may be more vulnerable to the cold, highly variable climatic conditions associated with these seasons. The objective of this study was to determine if late gestation shearing induces differences in individual BW, dry matter intake (DMI) and plasma metabolite concentration of finewool ewes managed outdoors during winter. Thirty-six mature, pregnant Rambouillet ewes (3.8±0.45 years; 76.8±11.4 kg) were managed in a drylot with ad libitum access to pelleted alfalfa in bunks capable of measuring individual daily DMI. The treatment group consisted of ewes sheared at ~5 weeks before the estimated parturition date (shorn; n=18). Unshorn ewes (n=18) remained in full fleece throughout the experiment and were shorn on the last day of the experiment ~2 weeks before the estimated parturition date. Blood was collected on days 0 (before shearing shorn group), 7, 14 and 21 (before shearing unshorn group) of the trial, and plasma was isolated and analyzed for non-esterified fatty acid (NEFA), β-hydroxybutyrate (BHB) and glucose (GLU) concentrations. There was no effect of shearing on ewe DMI or BW during the trial (P⩾0.35). Plasma NEFA and GLU concentrations were similar (P⩾0.36) between shearing groups, though plasma BHB concentration was 103.7 μmol/l greater (24.1%; P<0.01) in unshorn ewes. Lamb BW at birth was not affected (P=0.30) by ewe shearing treatment. Under conditions of this study, no differences in economically important aspects of sheep production were observed between shorn and unshorn pregnant ewes.     

Feeding a slowly digestible carbohydrate diet during pregnancy of insulin-resistant rats prevents the excess of adipogenesis in their offspring

An obesogenic environment during pregnancy has been shown to increase the risk of dysregulation on adipogenesis and insulin resistance in the offspring. Being essential for the growing fetus, glucose supply is guaranteed by a number of modifications in the mother’s metabolism, and thus, glucose control during pregnancy especially among obese or diabetic women is paramount to prevent adverse consequences in their children.Besides the election of low-glycemic-index carbohydrates, the rate of carbohydrate digestion could be relevant to keep a good glucose control. In the present study, we compared the effects of two high-fat diets with similar glycemic load but different rates of carbohydrate digestion given to pregnant insulin-resistant rats. After birth, all animals were fed a standard diet until age 14 weeks. We analyzed offspring body composition, plasma and adipocyte lipidomics, lipid metabolism in adipose tissue and insulin sensitivity. Those animals whose mothers were fed the rapid-digesting carbohydrate diet exhibited an excessive adipogenesis. Thus, these animals showed a marked lipidemia, increased lipid synthesis in the adipose tissue and reduced glucose transporter amount in the adipose. On the contrary, those animals whose mothers were fed the slow-digesting carbohydrate diet showed a profile in the measured parameters closer to that of the offspring of healthy mothers. These results support the hypothesis that not only glycemic index but the rate of carbohydrate digestion during gestation may be critical to regulate the programming of adipogenesis in the offspring.     

Maternal psychosocial stress during pregnancy alters the epigenetic signature of the glucocorticoid receptor gene promoter in their offspring: a meta-analysis

Prenatal stress has been widely associated with a number of short- and long-term pathological outcomes. Epigenetic mechanisms are thought to partially mediate these environmental insults into the fetal physiology. One of the main targets of developmental programming is the hypothalamic-pituitary-adrenal (HPA) axis as it is the main regulator of the stress response. Accordingly, an increasing number of researchers have recently focused on the putative association between DNA methylation at the glucocorticoid receptor gene (NR3C1) and prenatal stress, among other types of psychosocial stress. The current study aims to systematically review and meta-analyze the existing evidence linking several forms of prenatal stress with DNA methylation at the region 1_F of the NR3C1 gene. The inclusion of relevant articles allowed combining empirical evidence from 977 individuals by meta-analytic techniques, whose methylation assessments showed overlap across 5 consecutive CpG sites (GRCh37/hg19 chr5:142,783,607-142,783,639). From this information, methylation levels at CpG site 36 displayed a significant correlation to prenatal stress (r = 0.14, 95% CI: 0.05–0.23, P = 0.002). This result supports the proposed association between a specific CpG site located at the NR3C1 promoter and prenatal stress. Several confounders, such as gender, methylation at other glucocorticoid-related genes, and adjustment for pharmacological treatments during pregnancy, should be taken into account in further studies.     

High dietary intake of medium-chain fatty acids during pregnancy in rats prevents later-life obesity in their offspring

We investigated the effects of dietary fatty acids of different chain lengths during pregnancy in the rat on the susceptibility of offspring to later-life obesity and the underlying mechanisms. Pregnant rats were fed three different diets: standard (STD), high medium-chain fatty acids (MCFA); and high long-chain fatty acids (LCFA). The male offspring were assigned to three groups: STD control, MCFA and LCFA according to the maternal diets and suckled by dams fed with STD during pregnancy and lactation. After weaning, the offspring were fed with STD from 3 to 8 weeks of age. At the age of 8 weeks, rats in three groups: high-fat diet (HFD) control, MCFA and LCFA were fed with HFD until 14 weeks of age in an attempt to induce obesity, and rats in the HFD control group were selected randomly from the STD control group. Body weight and body fat content were decreased in the MCFA group accompanied by down-regulated mRNA expression of fatty acid synthase and acetyl-coA carboxylase 1, and increased mRNA and protein expression of adenosine monophosphate (AMP)-activated protein kinase (AMPK), carnitine palmitoyltransferase 1 and uncoupling protein 3 compared with the corresponding controls at 3, 8 and 14 weeks of age. The results suggested that the MCFA diet during pregnancy prevented later-life obesity in the offspring when they were exposed to HFD in later life, which might be related to programming of the expression of genes involved in fatty acid metabolism.     

Effect of maternal diet on offspring coping styles in rodents: a systematic review and meta‐analysis

Maternal nutrition can have long‐term effects on offspring morphology, physiology and behaviours. However, it is unclear whether mothers ‘program’ offspring behavioural coping strategy (proactive/reactive) according to the predicted nutritional quality of their future environment. We conducted a systematic review on this topic and meta‐analytically synthesized relevant experimental data on mice and rats (46 studies). We included data from experiments where dams were subjected to caloric restriction, protein restriction or overfeeding around gestation and subsequently measured offspring activity, exploration, or anxiety. Overall, little evidence existed for effects of maternal nutrition on the three investigated behavioural traits. The high heterogeneity observed in the data set suggests that maternal programming may sometimes occur. However, because offspring had access to a balanced diet before testing, behaviours may have been reprogrammed. Our results may indicate that reprogrammed behaviours could ameliorate negative effects associated with sub‐optimal nutrition in early life. Further, our systematic review revealed clear knowledge gaps and fruitful future research avenues.     

A methyl-deficient diet fed to rats during the pre- and peri-conception periods of development modifies the hepatic proteome in the adult offspring

A methyl-deficient diet (MD) lacking folic acid and the associated methyl donors choline and methionine, fed to the laboratory rat during the periods of oocyte and embryo development, has been shown to programme glucose metabolism in the offspring. The hepatic proteome of the male offspring of female rats fed MD diets for 3 weeks prior to mating and for the first 5 days of gestation has been examined by 2-dimensional gel electrophoresis. Three groups of differentially abundant proteins associated with energy metabolism, amino acid metabolism and antioxidant defence were identified in the soluble proteins extracted from the liver from the MD offspring at both 6 and 12 months of age. Altered mitochondrial activity in other programming models leads to a similar pattern of differential protein abundance. Two of the differentially abundant proteins were identified as GAPDH and PGK-1 by mass spectrometry. Western blotting showed that there were multiple isoforms of both proteins with similar molecular weights but different isoelectric points. The differentially abundant spots reduced in the MD offspring corresponded to minor isoforms of GAPDH and PGK-1. The levels of PPAR-alpha, SREBP and glucocorticoid receptor mRNAs associated with other models of prenatal programming were unchanged in the MD offspring. The data suggest that a diet deficient in folic acid and associated methyl donors fed during the peri-conception and early preimplantation periods of mammalian development affects mitochondrial function in the offspring and that the posttranslational modification of proteins may be important.     

Effect of the Japanese diet during pregnancy and lactation or post-weaning on the risk of metabolic syndrome in offspring

We examined the effects on offspring of ingestion of the 1975 Japanese diet during pregnancy and lactation and after weaning in mice. Pregnant dams were divided into groups that were fed the Japanese diet or a control diet and raised until offspring were weaned. The offspring after weaning were further divided into groups that were raised on the Japanese diet or the control diet. Ingestion of the Japanese diet after weaning suppressed accumulation of visceral fat in offspring, and reduced the amount of lipids in serum and liver. This effect was weakened if the Japanese diet was only ingested during pregnancy and lactation. Therefore, it was suggested that ingestion of the Japanese diet of mothers during pregnancy and lactation weakens the lipid accumulation inhibitory effect of the Japanese diet in children.     

Effect of different iodide intake during pregnancy and lactation on thyroid and cardiovascular function in maternal and offspring rats

ObjectiveWe aimed to investigate the impact of different iodide intake during pregnancy and lactation on iodine concentration in urine and serum, fatty acid metabolism, thyroid and cardiovascular function in maternal and offspring rats.MethodsPregnant rats were randomly assigned to four groups: normal adult iodide intake (NAI, 7.5 μg/d), normal pregnant iodide intake (NPI, 12.5 μg/d), 5 times (5 HI, 62.5 μg/d) and 10 times higher-than-normal pregnant iodide intake (10 HI, 125 μg/d). The maternal rats were continuously administered potassium iodide until postnatal day 16 (PN16). Thyroid function was measured by enzyme-linked immunosorbent assay (ELISA). The iodine concentration in urine and serum were detected by inductively coupled plasma mass spectrometry (ICP-MS). The messenger ribonucleic acid (mRNA) expressions of Krüppel-like factor 9 (KLF9) and thioredoxin reductase 2 (Txnrd2) were measured using quantitative real-time polymerase chain reaction (RT-qPCR). Characteristic distribution of KLF9 expression and its interaction with TRβ was assessed by immunohistochemical and immunofluorescence staining. Serum fatty acids were analyzed by Liquid Chromatography-Mass Spectrometry (LC-MS). Cardiac function and blood pressure were measured by echocardiography and a non-invasive tail-cuff system.ResultsHigh iodide intake (5 HI and 10 HI) during pregnancy and lactation results in increased urinary iodine concentration (UIC), serum total iodine concentration (STIC) and serum non-protein-bound iodine concentration (SNBIC) in both maternal and offspring rats, along with significantly increased FT3 and its target gene expression of KLF9. In maternal rats of both 5 HI and 10 HI groups, systolic blood pressure (SBP) was significantly higher, the increased SBP was significantly correlated with the increased UIC (r = 0.968, p = 0.002; r = 0.844, p = 0.035), KLF9 (r = 0.935, p = 0.006; r = 0.954, p = 0.003) and the decreased Txnrd2 (r = −0.909, p = 0.012; r = −0.912, p = 0.011). In maternal rats of 10 HI group, cardiac hyperfunction with increased LVEF, LVFS and decreased LVESD were observed. The increased LVEF and decreased LVESD were significantly correlated with UIC, STIC and SNBIC (r = 0.976, p = 0.001; r = 0.945, p = 0.005; r = 0.953, p = 0.003; r = −0.917, p = 0.01; r = −0.859, p = 0.028; r = −0.847, p = 0.033), LVEF, LVFS and LVESD were significant correlated with KLF9 (r = 0.950, p = 0.004; r = 0.963, p = 0.002; r = −0.990, p = 0.0002) and Txnrd2 expression (r = −0.979, p = 0.001; r = −0.915, p = 0.01; r = 0.933, p = 0.007), and the decreased LVESD was correlated with decreased epoxyeicosatrienoic acid (EET) metabolites: 5,6-EET, 8,9-DHET and 11,12-DHET (r = 0.999, p = 0.034; r = 1.000, p = 0.017; r = 1.000, p = 0.017). While in offspring rats, no significant change in SBP and cardiac function was found. STIC and SNBIC were much lower than those in maternal rats, and eicosapentaenoic acid (EPA) metabolites (9-HEPE, 15-HEPE and 14,15 DiHETE) were significantly increased.ConclusionIn addition to thyroid hormones, STIC, SNBIC, KLF9, Txnrd2, EET and EPA metabolites might be promising biomarkers in high iodide intake-induced thyroid and cardiovascular function.