Chronic maternal dietary iodine deficiency but not thiocyanate feeding affects maternal reproduction and postnatal performance of the rat

Iodine deficiency disorders affect reproductive performance in the afflicted populations. Environmental iodine deficiency (ID) and goitrogens are important in their aetiology. We observed earlier that chronic maternal dietary ID but not goitrogen feeding altered the blood-brain barrier nutrient transport in adult rats. Whether similar differences exist in their effects on reproduction of dams and postnatal performance of the offspring has been assessed. Inbred, female, weaning WNIN rats were rendered hypothyroid by feeding for 8-12 weeks, a low iodine test diet or a control diet with added potassium thiocyanate (KSCN) (@ 25 mg/rat/day). Following mating with control males, they continued on their respective diets till their pups were weaned. Indices of reproductive performance such as percentage of conception, mortality of dams during pregnancy and parturition, litter size, and survival of pups till weaning were affected markedly by ID but not thiocyanate feeding. Neither ID nor thiocyanate feeding from conception or parturition affected their reproductive performance. Nevertheless, postnatal weight gain of pups was less in all the three ID groups but not thiocyanate fed dams. Rehabilitation of chronically ID pregnant dams from conception or parturition did not improve their pregnancy weight gain, litter size or birth weight of pups but decreased abortion and mortality of mothers during pregnancy and parturition. Rehabilitation improved the pups' postnatal weight gain but the effect was only moderate. Based on the results of the present study it may be suggested that maternal ID but not thiocyanate feeding affects reproductive performance and postnatal performance of their offspring.     

Two-generation reproduction study of di-2-ethylhexyl terephthalate in Crl:CD rats

BACKGROUND: This study was conducted to evaluate the potential adverse effects of di-2-ethylhexyl terephthalate (DEHT) on reproductive capability from exposure of F(0) and F(1) parental animals. METHODS: Four groups of male and female Crl:CD (SD)IGS BR rats (30/gender/group) were exposed to 0, 0.3%, 0.6%, and 1.0% DEHT in the feed for at least 70 consecutive days before mating for the F(0) and F(1) generations. Exposure for the F(0) and F(1) males continued throughout the mating period until euthanasia. Exposure for the F(0) and F(1) females continued throughout mating, gestation, and lactation. The F(1) and F(2) pups were weaned on postnatal day (PND) 21. Assessments included gonadal function, estrous cyclicity, mating behavior, conception rate, gestation, parturition, lactation, and weaning in the F(0) and F(1) generations, and F(1) generation offspring growth and development. RESULTS: DEHT exposure did not affect clinical observations. However, lethality was observed in F(0) and F(1) dams consuming the 1.0% diet during the post-weaning period. No treatment-related mortality occurred in any of the male groups exposed to DEHT or in the female groups exposed to 0.3% or 0.6% DEHT. Male rats consuming the 1.0% diet in both parental generations gained weight more slowly than the controls. There were no indications of adverse effects on reproductive performance in either the F(0) or F(1) generation. Male and female mating and fertility indices, pre-coital intervals, spermatogenic endpoints, reproductive organ weights, lengths of estrous cycle and gestation, live litter size, developmental landmarks, and postnatal survival were similar in all exposure groups. Additionally, ovarian follicle counts for the F(1) females in the high-exposure group were similar to the control values. No adverse exposure-related macroscopic pathology was noted at any exposure level in the F(0) and F(1) generations. CONCLUSIONS: Increases in liver weights were found in the male and female animals exposed to 0.6% or 1.0% DEHT in the diet. Because there were no accompanying histopathologic changes, this effect was not considered adverse. Significant decreases in feed consumption in the female animals from the groups consuming 1.0% DEHT in the diet during lactation accompanied reduced postnatal pup body weights and rate of weight gain. Reductions in pup body weights later in lactation may also have been due to direct consumption of the treated feed by the pups or taste aversion to the same. Reduced relative spleen weight was found in male weanling pups from the 1.0% group in both generations and reduced relative spleen and thymus weights were found in female pups from the 1.0% group in the F(2) generation at necropsy on PND 21. Therefore, for parental and pup systemic toxicity, 0.3% DEHT in the diet (182 mg/kg/day) was considered no-observed-effect level (NOEL). The 1.0% DEHT (614 mg/kg/day) in the diet exposure concentration was considered a NOEL for F(0) and F(1) reproductive toxicity endpoints.     

Nicotine moderates the effects of macronutrient balance on nutrient intake by parasitized <Emphasis Type="Italic">Manduca sexta</Emphasis> L

Effects of dietary nicotine and macronutrient ratio on M. sexta larvae were examined. Larvae were fed a carbohydrate-biased, protein-biased or diet having equal amounts of casein and sucrose, with and without nicotine. Without nicotine, larvae displayed compensatory feeding on the low protein diet, but despite consuming more, grew least on this diet. Nicotine at 0.5% had no effect on nutrient consumption. Nicotine at 1.0 and 2.0% reduced overall consumption and thereby also reduced nicotine consumption. Larvae parasitized by C congregata displayed reduced nutrient intake and growth on all diets. Parasitized larvae responded to 1% nicotine similarly to unparasitized larvae. At 0.5% nicotine, they displayed reduced consumption on all diets, possibly due to altered chemoreceptor sensitivity to nicotine. When offered a choice of two diets having different macronutrient ratios, one with and the other without 0.1% nicotine, all larvae preferred the diet lacking nicotine and failed to regulate nutrient intake such that the nutrient intake target, a ratio of nutrients supporting optimal growth, was achieved. Parasitized larvae consumed less nicotine on a fresh weight basis than unparasitized insects, suggesting that the feeding response of parasitized larvae to nicotine minimizes the exposure of nicotine to developing parasites.     

Effects of restricted feeding of prepubertal ewe lambs on reproduction and lactation performances over two breeding seasons

The aim of this study was to determine the effects of restricted feeding before puberty on reproduction, lactation and offspring growth performance in replacement ewe lambs over two breeding seasons. At weaning, 41 Dorset ewe lambs were assigned to one of three diets: an ad libitum control diet with medium-quality forage (MQF; 13.3% crude protein (CP), 1.81 Mcal metabolizable energy per kg, 42.8% ADF; diet A-MQF); a restricted diet with the same forage as A but less feed concentrate (diet R-MQF); or a high-quality forage (HQF) diet (14.8% CP, 2.15 Mcal ME/kg, 34.7% ADF; diet F-HQF). The quantity of concentrate offered to the group R-MQF and F-HQF ewe lambs was adjusted to obtain 70% of the control ewe lambs' growth rate. The diets were offered for 75 days following weaning to cover the allometric phase of mammary gland development. Prepubertal restriction did not affect (P > 0.10) the gestation rate, number of lambs born or the body weight and body condition score of ewes at lambing or at the end of lactation. Ewes from groups R-MQF and F-HQF tended to produce more milk during their first lactation compared to those from group A-MQF (P = 0.07). During the second lactation, groups R-MQF and F-HQF had better standardized milk production than group A-MQF (P < 0.05), and group R-MQF produced more milk than group F-HQF (P < 0.05). Milk fat and protein content were not affected by treatments (P > 0.10) Fat and protein yield were affected by treatments only at the second lactation (P < 0.10 and P < 0.05, respectively). Lamb birth and weaning weights were not affected by prepubertal restriction of feeding in their mother (P > 0.10). However, the average daily gain of second breeding season lambs was higher for the R-MQF group than the F-HQF group (P < 0.05), and a similar trend was observed for total gain (P < 0.10). Restricted feeding before puberty does not impair future reproductive performance; however, it has a positive impact on lactation and on lambs' growth performance.     

High potassium diets markedly protect against stroke deaths and kidney disease in hypertensive rats, a possible legacy from prehistoric times

Male spontaneously hypertensive stroke-prone (SHRsp) rats were fed 4% NaCl diets containing either 0.75% (normal) K or 2.11% (high) K, starting at 6 weeks of age. After 8 months on these diets, 40 out of 58 SHRsp rats on the 0.75% K diet had died (69% mortality) versus 2 dead out of 95 on the 2.11% K diet (2% mortality), a 97% reduction in mortality, p less than 0.00001. After 20 weeks on the diets, the daytime and nighttime blood pressures of each rat were measured intraarterially under light ether anesthesia. Using these accurate blood pressures, we selected two groups precisely matched for blood pressure. One matched SHRsp group (BP 182) ate the 0.75% K diet and 30 out of 47 rats died (64% mortality). The other matched SHRsp group (BP 182) ate the 2.11% K diet and 2 out of 35 died (6% mortality), a 91% reduction of mortality, p less than 0.0001. Seemingly, this striking reduction in mortality rate with the 2.11% high K diet does not depend on a lowering of blood pressure. High K diets do not change body Na or K. Dry weight of mesenteric arterioles was reduced 29% on the 2.11% K diet versus the 0.75% K diet (5.43 vs. 7.66 mg) (p less than 0.0001), indicating a greatly reduced hypertensive hypertrophy. In nine surviving SHRsp rats on the 0.75% K diet, 13 of 36 brain hemisphere slides (4 slides per rat) showed infarcts (36%). In 11 surviving SHRsp rats on the 2.11% K diet, 1 of 44 brain slides showed infarcts (2%), a 94.5% reduction, p less than 0.0001.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of dietary sewage solids on second-generation ewes fed an experimental diet from weaning through two reproductive cycles

Eighteen fine-wool ewe lambs produced by mature, conventionally fed dams and 21 similar offspring from sewage-fed ewes were randomly allotted at weaning to one of two groups. Half of the lambs from each maternal diet group received a conventional (18% protein) diet during the growing phase while the remainder was fed the conventional diet plus 7% undigested, irradiated sewage solids (18% protein). At the end of the 147-day growing period and just before a fall breeding season, conventionally fed ewe lambs were switched to a control diet (12% protein) suitable for mature ewes and sewage-fed ewe lambs began receiving the control diet plus 7% sewage solids. Animals received these diets for two years. Maternal sewage consumption did not influence performance of F₁ ewe lambs. By the beginning of the first breeding season, controls were heavier (P<0.01) than were animals receiving sewage solids (51.7 and 44.5 kg, respectively). Similarly, only 75% of sewage-fed ewe lambs exhibited estrus during their first breeding season compared with 94.7% of controls (P<0.10). Conception rate (40.0 and 84.2%, respectively) and lambs born per ewe exposed (0.4 and 0.89, respectively) were also lower (P<0.05) in animals receiving sewage solids than in controls. During the second reproductive cycle, conception rate as well as lambs born per ewe exposed was comparable (P>0.10) between the two groups. Offspring from the sewage-fed ewe lambs, however, weighed less (P<0.05) at weaning than did lambs produced by control animals. Results indicate that a diet containing 7% sewage solids may not be suitable for preparing ewe lambs to go into the breeding flock; once mature size is attained, however, reproductive performance is not hampered by sewage feeding.     

Maternal effects are long‐lasting and influence female offspring's reproductive strategy in the swordtail fish Xiphophorus multilineatus

The adaptive benefits of maternal investment into individual offspring (inherited environmental effects) will be shaped by selection on mothers as well as their offspring, often across variable environments. We examined how a mother's nutritional environment interacted with her offspring's nutritional and social environment in Xiphophorus multilineatus, a live‐bearing fish. Fry from mothers reared on two different nutritional diets (HQ = high quality and LQ = low quality) were all reared on a LQ diet in addition to being split between two social treatments: exposed to a large adult male during development and not exposed. Mothers raised on a HQ diet produce offspring that were not only initially larger (at 14 days of age), but grew faster, and were larger at sexual maturity. Male offspring from mothers raised on both diets responded to the exposure to courter males by growing faster; however, the response of their sisters varied with mother's diet; females from HQ diet mothers reduced growth if exposed to a courter male, whereas females from LQ diet mothers increased growth. Therefore, we detected variation in maternal investment depending on female size and diet, and the effects of this variation on offspring were long‐lasting and sex specific. Our results support the maternal stress hypothesis, with selection on mothers to reduce investment in low‐quality environments. In addition, the interaction we detected between the mother's nutritional environment and the female offspring's social environment suggests that female offspring adopted different reproductive strategies depending on maternal investment.     

Effects of class-specific,synthetic, and natural proteinase inhibitors on life-history traits of the cotton bollworm Helicoverpa armigera

Herbivorous insects have more difficulty obtaining proteins from their food than do predators and parasites. The scarcity of proteins in their diet requires herbivores to feed voraciously, thus heavily damaging their host plants. Plants respond to herbivory by producing defense compounds, which reduce insect growth, retard development, and increase mortality. Herbivores use both pre- and postdigestive response mechanisms to detect and avoid plant defense compounds. Proteinase inhibitors (PIs) are one example of plant compounds produced as a direct defense against herbivory. Many insects can adapt to PIs when these are incorporated into artificial diets. However, little is known about the effect of PIs on diet choice and feeding behavior. We monitored the diet choice, life-history traits, and gut proteinase activity of Helicoverpa armigera larvae using diets supplemented with synthetic and natural PIs. In choice experiments, both neonates and fourth-instar larvae preferred the control diet over PI-supplemented diets, to varying degrees. Larvae that fed on PI-supplemented diets weighed less than those that fed on the control diet and produced smaller pupae. Trypsin-specific PIs had a stronger effect on mean larval weight than did other PIs. A reduction of trypsin activity but not of chymotrypsin activity was observed in larvae fed on PI-supplemented diets. Therefore, behavioral avoidance of feeding on plant parts high in PIs could be an adaptation to minimize the impact of this plant's defensive strategy.     

Developmental aluminum toxicity in mice can be modulated by low concentrations of minerals (Fe,Zn, P,Ca, Mg) in the diet

Female Swiss Webster mice were fed diets containing 7 (control) or 1000 μg Al/g diet from conception to weaning. Pregnancy weight gain, brith weight, litter size, postnatal mortality, and weaning weight were measured. In different groups, diets low in Fe, Zn, P, or Ca and Mg (CaMg) were used as basal diets, to which Al was added. Relative to controls, who received NRC recommended levels of these nutrients, all diets with marginal essential trace elements impacted development, as demonstrated by effects on birth weight (CaMg, Fe) or weaning weight (Fe, Zn, P). Compared to diets low in Al, the 1000-mg Al/g diet led to reduced weaning weight regardless of the essential element content of the diet. Other end points were influenced by Al only within the basaldiet group; pregnancy weight gain with the low-P diet, litter size with the low-Fe diet, pregnancy completion with the low-Zn diet, and postnatal mortality with the low-CaMg or low-Zn diet. Thus, diets marginal in selected minerals can differentially alter the toxicological profile of developmental Al exposures. A basal diet was also used in which the NRC diet was supplemented with ascorbic acid, which promotes Al absorption. No modification of Al toxicity was seen with ascorbic acid supplementation.     

Effects of azadirachtin on the nutrition and development of the tobacco budworm,Heliothis virescens (Fabr.) (Noctuidae)

The plant chemical azadirachtin was administered, either in artificial diet or by oral injection, to fifth instar larvae of the tobacco budworm, Heliothis virescens (Fabr.). At a dietary concentration of 0.03125 ppm, azadirachtin significantly reduced the amount of diet consumed and the weight gained by the larvae. Higher dietary concentrations (0.25 and 0.5 ppm) were necessary to reduce the efficiency of larval conversion of digested and ingested food, respectively. However, the approximate digestibility increased at the dietary concentration of 0.25 ppm.Orally injected azadirachtin (0.25 and 0.5 μg) delayed moulting to the pupal stage, produced defective pupae or adults, and inhibited development to the adult stage. Higher doses (5.0 and 10.0 μg) reduced the pre-pupal weight loss normally associated with pupation, and completely inhibited pupation. At the critical dose of 1.0 μg (the minimal dose that disrupted development to the pupal stage), azadirachtin had less of an effect on older than on younger larvae. Larvae injected on the first day of the fifth instar failed to pupate, whereas approx 40% of those injected on subsequent days pupated.The results suggest that azadirachtin affects H. virescens in a manner similar to other tested species of insects. The significance of these results, especially regarding hormonal events in the insects, is discussed.     

Effects of four monoterpenoids on growth and reproduction of the German cockroach (Blattodea: Blattellidae).

The effects of the monoterpenoids d-limonene, linalool, beta-myrcene, and alpha-terpineol on the growth and development of the German cockroach Blattella germanica (L.) were examined. We evaluated the chemicals' attractiveness in cockroach diet, quantified growth effects induced by monoterpenoids, examined embryotoxic properties of the compounds, and examined their effects on reproduction when administered by oral, topical, and vapor routes of entry. Untreated diet was significantly preferred compared with diet treated with high levels of d-limonene, linalool, and alpha-terpineol. The threshold for acceptance was between 1 and 10% (AI). All four monoterpenoids significantly influenced the days required by nymphs to reach the adult stage; in general, higher monoterpenoid concentrations in the diet were associated with a reduction in the days required by nymphs to mature. Application of high doses of d-limonene or linalool to oothecae of gravid female cockroaches significantly decreased the probability of young emerging from them but did not affect female mortality. Feeding on diet treated with monoterpenoids during nymphal development and through the early, premating period of the adult stage did not significantly influence numbers of broods produced per pair, numbers of offspring per brood, days required to produce a brood, total offspring produced by a pair, or female life span. Topical applications of linalool, beta-myrcene, or alpha-terpineol at near lethal rates to adult cockroaches before they mated had no significant influence on the reproductive parameters examined. A single exposure to sublethal levels of monoterpenoid vapors before mating had no significant influence on any reproductive parameters examined.     

Effects of maternal diet quality on offspring performance in the rove beetle Tachyporus hypnorum

Abstract.  1. The reproductive output of an individual is known to be influenced by diet quality, but the quality of the parent's diet can also influence the performance of the offspring. Dietary maternal effects may interact with the effects of the offspring's diet to produce a variety of response patterns.
2. Maternal effects were investigated in a polyphagous predator, the rove beetle Tachyporus hypnorum , using three single-species diets: two low-quality diets consisting of the aphids Sitobion avenae and Rhopalosiphum padi , and the high-quality control Drosophila melanogaster diet. Offspring of females fed these diets were raised on the same monotypic diets and allowed to reproduce. Several fitness parameters were measured to indicate possible maternal effects in both F1 and F2 generations.
3. Maternal diet effects in F1 were found in egg size, hatching success, time to hatching, larval development time, larval survival, and sex ratio. Both aphid diets resulted in smaller eggs. A diet of R. padi resulted in reduced hatching success, longer time spent in the egg stage, and a female-biased sex ratio. A maternal diet of R. padi also prolonged larval development on S. avenae diet, while a maternal diet of S. avenae decreased survival on the R. padi diet. These effects were independent of egg size.
4. A maternal diet of R. padi enhanced the survival of F1 larvae raised on the same diet. Developmental selection operating through a high egg mortality may be the explanation for this seemingly positive effect.
5.  Sitobion avenae alone caused a significant reduction in the hatching success of F2 eggs, thus revealing grandmaternal effects.
6. The prediction that polyphagous predators are less likely to evolve adaptive maternal effects is supported by the fact that none of the documented maternal effects could be interpreted as adaptive.     

Effects of dietary omega-3 PUFAs on growth and development: Somatic,neurobiological and reproductive functions in a murine model

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) are relevant to fetal and infant growth and development. Objective: to assess whether long-term exposure to dietary ω-3 PUFA imbalance alters pre- and/or postnatal pups' development and reproductive function later in life. Mice dams were fed with ω-3 PUFA Control (soybean oil, 7%), Deficient (sunflower oil, 7%) or Excess (blend oil; 4.2% cod-liver+2.8% soybean) diet before conception and throughout gestation-lactation and later on, their pups received the same diet from weaning to adulthood. Offspring somatic, neurobiological and reproductive parameters were evaluated. Excess pups were lighter during the preweaning period and shorter in length from postnatal day (PND) 7 to 49, compared to Control pups (P<.05). On PND14, the percentage of pups with eye opening in Excess group was lower than those from Control and Deficient groups (P<.05). In Excess female offspring, puberty onset (vaginal opening and first estrus) occurred significantly later and the percentage of parthenogenetic oocytes on PND63 was higher than Control and Deficient ones (P<.05). Deficient pups were shorter in length (males: on PND14, 21, 35 and 49; females: on PND14, 21 and 42) compared with Control pups (P<.05). Deficient offspring exhibited higher percentage of bending spermatozoa compared to Control and Excess offspring (P<.05). These results show that either an excessively high or insufficient ω-3 PUFA consumption prior to conception until adulthood seems inadvisable because of the potential risks of short-term adverse effects on growth and development of the progeny or long-lasting effects on their reproductive maturation and function.     

The dietary effects of 20-hydroxyecdysone on the development of housefly

The ingestion of 20-hydroxyecdysone adversely affected the growth and development of housefly larvae (Musca domestica) reared axenically on two synthetic diets. In a casein diet, this hormone was toxic causing 84% mortality at a concentration of 100 ppm. In an amino acid diet, the mortality was 65% at 100 ppm but the rate of larval development was greater than the controls and some puparia showing prothetely were produced for all concentrations tested. The different effects can be explained in terms of differences in the absorption and/or catabolism of 20-hydroxyecdysone in the two diets.     

Common ringtail possum (Pseudocheirus peregrinus) as a management model for the Pseudocheiridae: Reproductive scope,behavior, and biomedical values on a browse-free diet

The purposes of this study were to determine 1) the life history characteristics of a captive colony of the arboreal folivore Pseudocheirus peregrinus maintained on a browse free diet under enhanced laboratory conditions, 2) the direction and magnitude of life history differences from wild population values, and 3) the feasibility of developing captive colonies of this and related species for conservation and research programs. Rates of reproduction, growth, and development; demographic trends; behavioral patterns pertinent to exhibition; and management and medical techniques are reported. Fecundity was 67% greater than that of wild populations and there was an approximate four-fold increase in the rate of offspring survival to sexual maturity. These trends were due largely to reduced post-pouch emergence mortality and the decay of reproductive seasonality. The results indicate that a properly designed “artificial” diet can support significantly enhanced reproduction in a trophic specialist. Other demographic, developmental, and behavioral measures found to be consistent with those reported from wild populations indicate that there was no significant life history distortion caused by the management regime. Empirical data are presented showing that the common ringtail is nocturnal, has low rates of activity, and has specific space and substrate preferences. These results suggest ways in which the animals' physical environment can be manipulated to improve exhibition. We conclude that the reproductive rates of other ringtail possum species might also be enhanced under comparable management conditions.     

Diet,maternal condition,and offspring sex ratio in the zebra finch,Poephila guttata

Where maternal condition affects condition and reproductive potential of offspring differentially with respect to sex, mothers in relatively good condition should produce more of the sex whose fitness is more dependent on condition. We experimentally manipulated body-condition in unmated zebra finches by feeding them for three months on high- or low-quality diets. Birds were then allowed to breed, while keeping the same diets. Females on the lower quality diet were in better condition and hatched significantly more males than females. Poorer condition females hatched an equal sex ratio. Chicks fed on the low-quality diet, but not on the high-quality diet, showed female-biased mortality. These results show that facultative sex ratio manipulation and sex-biased mortality can act together to produce extreme sex ratios in this vertebrate.     

Reproductive and genetic effects of continuous prenatal irradiation in the pig

The stem germ cells of the prenatal pig are highly vulnerable to the cytotoxic effects of ionizing irradiation. This study was conducted to determine whether sensitivity to killing was also marked by a sensitivity to mutation and how prenatal depletion of the germ-cell population affects reproductive performance. Germ-cell populations were reduced by continuously irradiating sows at dose rates of either 0.25 or 1.0 rad/day for the first 108 days of gestation. The prenatally irradiated boars were tested for sperm-producing ability, sperm abnormalities, dominant lethality, reciprocal translocations, and fertility. Prenatally irradiated females were allowed to bear and nurture one litter, then tested for dominant lethality in a second litter; germ cell survival and follicular development were assessed in their serially sectioned ovaries. Sperm production was not significantly affected in the 0.25-rad boars, but boars irradiated with 1.0 rad per day produced sperm at only 17% of the control level. Incidence of defective sperm was 4.9% and 11.1% in the 0.25 and 1.0 groups, respectively. Four of the 1.0-rad boars were infertile, but prenatal irradiation apparently caused neither dominant lethality nor reciprocal translocations in fertile males. Number of oocytes was reduced to 66 +/- 7% of control in the 0.25-rad gilts, but reproductive performance was unaffected and no dominant lethality was observed. Only 7 +/- 1% of the oocytes survived in the 1.0-rad group. Reproductive performance was normal for the first litter, but four of the 23 sows tested were infertile at the second litter and a significant incidence of dominant lethality was observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fetal origins of hyperphagia, obesity, and hypertension and postnatal amplification by hypercaloric nutrition

Environmental factors and diet are generally believed to be accelerators of obesity and hypertension, but they are not the underlying cause. Our animal model of obesity and hypertension is based on the observation that impaired fetal growth has long-term clinical consequences that are induced by fetal programming. Using fetal undernutrition throughout pregnancy, we investigated whether the effects of fetal programming on adult obesity and hypertension are mediated by changes in insulin and leptin action and whether increased appetite may be a behavioral trigger of adult disease. Virgin Wistar rats were time mated and randomly assigned to receive food either ad libitum (AD group) or at 30% of ad libitum intake, or undernutrition (UN group). Offspring from UN mothers were significantly smaller at birth than AD offspring. At weaning, offspring were assigned to one of two diets [a control diet or a hypercaloric (30% fat) diet]. Food intake in offspring from UN mothers was significantly elevated at an early postnatal age. It increased further with advancing age and was amplified by hypercaloric nutrition. UN offspring also showed elevated systolic blood pressure and markedly increased fasting plasma insulin and leptin concentrations. This study is the first to demonstrate that profound adult hyperphagia is a consequence of fetal programming and a key contributing factor in adult pathophysiology. We hypothesize that hyperinsulinism and hyperleptinemia play a key role in the etiology of hyperphagia, obesity, and hypertension as a consequence of altered fetal development.     

Increased incidence of hepatic insulin-sensitizing substance (HISS)-dependent insulin resistance in female rats prenatally exposed to ethanol

Insulin causes the release of the hepatic insulin-sensitizing substance (HISS) from the liver. Hepatic parasympathetic nerves play a permissive role in the release of HISS. HISS-dependent insulin resistance (HDIR) occurs in the absence of HISS. Fetal ethanol exposure has been shown to cause dose-dependent HDIR in adult male rat offspring. Since female offspring are more severely affected by in utero ethanol toxicity, we hypothesized that fetal alcohol exposure causes higher incidence and more severe HDIR in adult female offspring. Adult female rat offspring prenatally exposed to different concentrations of ethanol (0%, 15%, and 20%) were tested for insulin sensitivity using the rapid insulin sensitivity test (RIST). The RIST index was significantly reduced in the 15% (134.1 +/- 16.1 mg/kg) and the 20% (98.7 +/- 9.7 mg/kg) group compared with the 0% (220.9 +/- 27.6 mg/kg) group. Administration of atropine produced significant additional HDIR in the 15% group (82.9 +/- 14.5 mg/kg) but not the 20% group (83.8 +/- 20.5 mg/kg) indicating complete HDIR had been produced in this group, contrary to the adult male offspring in a previous study. The results are consistent with the hypothesis that adult-female offspring are more severely affected by in utero ethanol exposure compared with adult-male offspring.     

Fertility of transgenic female mice expressing bovine growth hormone or human growth hormone variant genes

Although growth hormone (GH) exerts various direct and indirect stimulatory effects on gonadal development and function, excessive levels of GH in acromegalic patients and in transgenic animals are often associated with reproductive disorders. We have examined reproductive performance of transgenic female mice expressing the following hybrid genes: mouse metallothionein-1 (MT)/human placental GH variant (hGH.V), MT/bovine GH(bGH), and phosphoenolpyruvate carboxykinase (PEPCK)/bGH. This allowed us to evaluate the effects of chronic GH excess in three animal models and to obtain some information on the significance of the lactogenic activity of the foreign GH (hGH.V vs. bGH) and on the developmental stage of transgene expression (MT vs. PEPCK). Transgenic animals from each line had elevated plasma insulin-like growth factor-I levels and greatly increased adult body weight. Plasma bGH levels were significantly higher in PEPCK/bGH than in MT/bGH transgenic mice. Approximately 20% of transgenic MT/hGH.V and MT/bGH females and over 60% of transgenic PEPCK/bGH females were infertile. Transgenic females that did reproduce ovulated either a normal or increased number of eggs but exhibited a variety of reproductive disorders including increased interval between pairing with a male and conception, increased interval between litters, reduced number of litters, reduced fetal growth, increased pre- and postnatal mortality, and alterations in sex ratio. Among adult offspring of these females, the proportion of transgenic animals was significantly less than the expected 50%. While some characteristics (e.g., fetal crown-rump length and weight on Day 14 of pregnancy) were affected to a comparable extent in transgenic females from all three lines, MT/hGH.V and PEPCK/bGH females were, in general, more severely affected than the MT/bGH animals. Sterility of PEPCK/bGH females appeared to be due to luteal failure since treatment with progesterone led to pregnancy. Greatly increased intervals between successive litters appeared to be due to failure to mate during postpartum estrus and to sterile matings during this period. Reduced fetal size and weight may have been due to chronic glucocorticoid excess because comparable changes could be induced in normal females by injections of dexamethasone during pregnancy, and plasma corticosterone levels were previously shown to be elevated in transgenic mice from each of these lines. Comparison of these results with data obtained from matings of normal female mice to transgenic males from the same lines suggests that reduced fetal growth is due primarily to maternal genotype, while reduced "transmission" of the hybrid genes is not, and presumably reflects increased mortality of transgenic progeny at various stages of development.(ABSTRACT TRUNCATED AT 400 WORDS)