Gestational zinc deficiency amplifies the regulation of metallothionein induction in adult mice

To determine if prenatal zinc deficiency has a persistent effect on metallothionein (MT) regulation, Swiss-Webster mice were mated and fed a diet containing either control (100 micrograms Zn/g) or low levels of zinc (5 micrograms Zn/g) from Day 7 of gestation to parturition. After birth all mice were given the control diet. Liver zinc and MT levels were 50% lower in newborn pups from dams fed the low zinc diets than in control pups. In control pups, liver zinc and MT concentrations were relatively stable during the first week of postnatal life. In contrast, in pups prenatally deprived of zinc, liver levels of zinc and MT increased such that by Day 3 of postnatal life, the levels were not significantly different from controls. At Day 56, serum IgM concentrations were significantly lower in the low zinc offspring. Liver zinc concentrations in the two groups of mice were similar at Day 70 postnatal, and in both groups liver MT levels were below detection limits. However, when Day 70 mice were given zinc injections to stimulate MT synthesis, the prenatally zinc deprived offspring showed markedly higher liver MT levels than did control mice given similar injections, despite similar liver zinc concentrations in the two groups. These results show that prenatal zinc deficiency has pronounced effects on postnatal MT metabolism which can persist into adulthood.     

Effects of age and biotin status on postnatal development of plasma biotinidase activity in rats

Biotinidase activity was measured in plasmas of 1-, 7-, 14-, and 21-day-old rats from control dams and dams that had been fed a biotin-depleting diet from Day 15 of gestation. Biotinidase activity increased significantly in the plasma of rats from control and depleted mothers until Postnatal Day 14, after which there was a small but significant decline at Day 21. Differences between the mean activities of the two groups of pups on each sampling day were not significant and there were no significant differences in activity levels attributable to sex. Plasma albumin concentrations increased from birth until Day 21, and plasma biotinidase activity and albumin concentration were significantly correlated (r = +/- 0.43). We suggested that these two proteins may be controlled by a common mechanism in the early postnatal period, and that biotin deficiency does not affect the development of biotinidase activity. Because biotin-depleted neonatal pups show developmental changes in biotinidase activity similar to those of human newborns, and they can be produced reliably by depleting dams from Day 15 of gestation, they may be useful models for studying the developmental abnormalities associated with human biotinidase deficiency.     

Evidence that suckling pups, through an exteroceptive mechanism, inhibit the milk stimulatory effects of prolactin in the rat during late lactation

Lactating rats were removed from the animal room on postpartum Day 20 and placed in a room where there were no other rats. On postpartum Day 21, these rats released prolactin either in response to exteroceptive signals from their own pups which were placed underneath or in response to those from 25 to 30 other lactating rats which along with their litters were placed in a rack 3 ft in front of the mothers' cage. Milk secretion was stimulated in the isolated rats on Day 21 by the prolactin released in response to exposure to the rack of lactators, but paradoxically was not stimulated by that released in response to exposure of the mother to her own pups. In fact, the stimulatory effects upon milk secretion, resulting from exposure to the rack of lactators was totally prevented if the mother was exposed to her pups 3–4 min before exposure to the rack of lactators. The blocking effect of the pups, however, did not occur when the pups were placed in cages alongside the mothers' cage. From subsequent experiments, it was concluded that sensory cues, from the pups, appeared to activate the sympathetico-adrenal system of the mother to release catecholamines which then blocked the milk stimulatory effects of prolactin which already had been discharged into the circulation. The pups did not inhibit milk secretion on Day 14 which indicates that the inhibiting mechanism becomes established sometime between Days 14 and 21 of lactation. These data suggest that a peripheral mechanism may operate to reduce milk secretion in the rat during late lactation, and thus, may be involved in the normal weaning process.     

The role of the young in the control of the hormonal events during lactation and behavioral weaning in the golden hamster

This study was designed to determine the relationship between the behavioral and physiological changes occurring in the hamster over the course of lactation. Experimental (E) females were given litters of six 3-day-old pups on Day 13 of lactation and allowed to raise them. Control (C) females raised their own litters of six pups. Groups of E and C females were decapitated at 1000 and 1700 hr when their pups were either 8, 18, or 28 days old. Nursing was observed for 1 hr on the 3 days prior to autopsy. Nursing behavior disappeared by Day 28 in C females. E females exhibited nursing behavior at levels equal to those observed in C females until E pups were 28 days old and 38 days had elapsed since parturition. Despite the fact that E mothers continued to nurse pups on day 18 postpartum when pups were 8 days old, E pups showed lower growth rates than did C pups. Prolactin (PRL) levels remained elevated when E pups were 8 days old even though E pups did not grow normally. PRL levels decreased over time in both C and E females and reached baseline by Day 28 although nursing behavior was still elevated in E females. Thus, nursing behavior did not stimulate PRL release during late lactation. Estradiol (E₂) levels in C females remained at baseline until Day 28 when levels increased. LH, FSH, and Progesterone (P) levels in C females showed a dramatic diurnal pattern which disappeared by Day 28, when levels dropped. Levels of E₂, P, LH, and FSH in E females closely paralleled those of C females only when groups were compared with respect to pup age. Thus, behavioral weaning and the return to estrous cyclicity appear to be dependent upon the age of the pups rather than the time elapsed since parturition. However, milk production and PRL release appear to be more closely tied to the number of days postpartum and can be dissociated from the amount of nursing behavior observed.     

Precocious induction of hepatic glucokinase and malic enzyme in artificially reared rat pups fed a high-carbohydrate diet

Glucokinase and NADP:malate dehydrogenase (malic enzyme) first appear in liver when rat pups are weaned from milk which is high in fat to lab chow which is high in carbohydrate. To examine the influence of diet during the early neonatal period, before developmental changes in the circulating concentrations of thyroid and adrenocortical hormones occur, high-carbohydrate formula (56% of calories from carbohydrate), isocaloric and isonitrogenous with rat milk, was intermittently infused via gastrostomy starting on the second day of life. Pups had no further access to their dams. Body weights attained by these pups were at least 90% of those attained by mother-fed pups, which served as controls. In artificially reared rats fed the high-carbohydrate formula, on Day 4, glucokinase and malic enzyme were 30 and 18% of adult activity, respectively; on Day 10, glucokinase and malic enzyme were 71 and 96% of adult activity, respectively. On Days 4 and 10 glucose-6-phosphate dehydrogenase was elevated four- to fivefold in pups fed the high-carbohydrate formula compared to mother-fed pups. A second isocaloric formula, with 22% of calories from carbohydrate but low in protein, resulted in intermediate levels of all three enzymes on Day 10. Pups fed the high-carbohydrate formula has plasma insulin concentrations four- to fivefold greater than mother-fed pups on both Days 4 and 10. Triiodothyronine administration (1 microgram/g body wt) on Day 1 enhanced the induction of malic enzyme but not glucokinase on Day 4 in pups fed the high-carbohydrate formula. The results demonstrate that neonatal rat liver is competent to respond to high carbohydrate intake by induction of glucokinase and malic enzyme.     

Neuroprotective activity of cannabinoid receptor‐2 against oxidative stress and apoptosis in rat pups having experimentally‐induced congenital hypothyroidism

In this study, it was aimed to show the cannabinoid receptor‐2 (CB2) role, which is a part of neuroprotective endocannabinoidal system, against increasing nitric oxide synthetase (iNOS, eNOS) levels and the apoptotic activity (caspase‐3, caspase‐9, and DNA in situ fragmentation) within the postnatal critical period in pups of pregnant rats with artificially induced maternal thyroid hormone (TH) deficiency. Each of the three groups established comprised one male and two female rats, and they were coupled. Their pups were used. In the first two groups, the mothers were treated with 0.025% MMI during the critical period of the pregnancy. In the third group, as the control group, the mothers and pups were not treated. Euthanasia was applied to the pups in Group I on Day 10, and to the pups in Groups II and III on Day 21. In the biochemical analyses, total T4 levels of both mothers and pups in Group I and II were found to be lower than those of the control group. Histopathologically, karyopyknosis in migrating neurons and demyelinization were observed in both groups. Caspase‐3 and −9 expressions and TUNEL reactions showed parallelism to these findings. eNOS and iNOS activities were also increased in Groups I and II. CB2 receptor activity was observed in the fore and mid brain in Group I, and in the whole brain in Group II. In conclusion, apoptosis was triggered via oxidative stress in hypothyroid pups. Accordingly, neuroprotective activity of CB2 receptors were motivated spontaneously to resist to CNS lesions during the first 3 weeks of postnatal period. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1334–1347, 2017     

Effects of excess methionine on collagen metabolism: a study on newborn rat skin

We studied the biochemical effects of excess methionine intake on the skin of newborn rats. Group 1 pups were intubated with methionine dissolved in 0.1 ml physiological saline solution in the amount of 0.1 g/100 body wt as a control using a gastric needle. Group 2 pups were given 0.2 g/100 g in the same manner as group 1 as an experimental group. They were intubated every other day from day 3 to 13. On Day 15, [14C]proline was injected intraperitoneally into pups and their skin was removed. 14C total and hydroxyproline uptake was examined in the tissue as well as in the sequential extracts. Although excess methionine intake by the pups did not alter the collagen content of their skin, it caused an increase in the content of type III collagen and a decrease in crosslinked collagen. In addition, newly synthesized collagen in the neutral salt extract increased in the excess methionine group, indicating that crosslinked collagen decreases as excess methionine was intubated. The present study demonstrated that excess methionine in the early lactational period altered the nature of the skin collagen of suckling newborn rat pups.     

Effects of diabetes on development of small intestinal enzymes of infant rats

The effect of streptozotocin (SZ) on the development of small intestinal enzymes in postnatal rat pups was studied. SZ was injected ip on Day 10 and, if necessary, again on Day 12. On Days 15, 18, and 21, one pup from each group (including a vehicle-injected control (C) group) was decapitated under conditions which minimized stress. Plasma glucose, insulin (IRI), and corticosterone were measured, as were pancreatic IRI, liver glycogen, and liver membrane binding of IRI. Small intestinal segments were processed and analyzed for sucrase, lactase, maltase, and ileal acid beta-galactosidase activities. Our results indicate that plasma glucocorticoid levels remained virtually constant in both SZ and C groups, while the ontogenic profiles of sucrase and maltase in SZ rats were shifted toward an earlier appearance and a precocious maturation. Circulating levels of IRI were not reduced significantly by SZ despite the fact that pancreatic IRI was decreased 95%. Jejunal lactase, unlike data reported for diabetic rats, was not affected by SZ diabetes. Also, acid beta-galactosidase was unaltered in the SZ rat pups. It is concluded that possibly the elevated disaccharidases seen in diabetic postnatal rat pups are the direct effect of elevated blood glucose. If so, the SZ rat pup model may be a useful tool with which to study effects of glucose on intestinal enzymes in the absence of changes in plasma insulin.     

Leptin treatment during lactation increases transfer of iodine through the milk

We have previously shown that protein restriction during lactation is associated with changes in iodine secretion into the milk and that a pup's serum leptin concentration was increased at the end of lactation. So, here we evaluate whether leptin treatment during lactation affects iodine transfer through the milk to the pups. Lactating rats were divided into two groups: the leptin (Lep) group, single injected with recombinant rat leptin (8 microg/100g of body weight, daily for 3 consecutive days), and the control (C) group that received the same volume of saline. We studied iodine transfer to the pups through the milk on Days 4, 12 and 21 of lactation. In those days, the dams were separated from their pups for 4 h. Then, the mothers received an injection of 131I (2.22x10(4) Bq ip) and the pups were allowed to nurse for 2 h. The animals were sacrificed 2 h later. Leptin, total serum T3 and total serum T4 concentrations were higher (P<.05) in pups of Lep mothers only on Day 4, suggesting a higher transfer of leptin through the milk at this period, probably with a direct stimulatory effect on thyroid hormone secretion. In other periods, however, even without a detectable increase in a pup's serum leptin concentration, maternal leptin administration increased the pup's thyroid iodine uptake (Day 12, 39%; Day 21, 34%), probably caused by a higher transfer of iodine through the milk, since they had a higher gastric content of 131I on Days 12 (31%) and 21 (128%).     

Lactational performance, consummatory behavior, and suppression of estrous cyclicity in rats suckling underfed pups

The role of pups' appetite in the regulation of maternal consummatory behavior (food intake of nursing mothers), lactational performance and postpartum diestrus was studied over a period of 45 days postpartum in rats chronically exposed to either underfed or normally fed pups. Experimental rats (n = 10) daily received 5 pups, 4-10-days-old, that had been deprived of food for the preceding 24 h while under the care of nonlactating foster mothers. Control rats (n = 10) received normally fed pups obtained daily from lactating foster mothers. Throughout the experimental period, the daily milk yield (estimated by litter weight gain), the intake of food and water by the mother, as well as the ratio of litter weight gain to mother's intake of food and water were all markedly higher in rats nursing underfed pups than in rats nursing normally fed pups. After a peak in lactation around Day 15 postpartum, experimental rats produced the same amount of milk during extended lactation as they did in the beginning of lactation, while control rats produced only half the amount of milk during extended lactation as they did in early lactation. Regardless of the nutritional state of the suckling pups, maternal body weight increased progressively over the first four weeks of lactation and remained unchanged during the time of extended lactation. The postpartum diestrus and the subsequent diestrous phase in the time of extended lactation were considerably longer in duration in rats that nursed underfed pups. On Day 45 of lactation, prolactin levels were higher and the adrenal glands were larger in experimental rats than in controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lactational [correction of Lacational] anovulation in rats and its dependency on progesterone

The relationship between prolactin (PRL) secretion and anovulation in lactating rats was studied. Normal lactating rats and lactating rats treated with antiserum against luteinizing hormone-releasing hormone at the time of postpartal ovulation were used. Normal lactating rats were treated with either a dopamine agonist (CB-154, 150 micrograms/rat) on Day 10 or 13, or pups removal on Day 7 or 10, and thereafter luteolysis and inhibition on PRL secretion were assessed. With the CB-154 treatment, the incidence of luteolysis increased as the lactational period advanced (42% vs 72%), whereas it decreased (73% vs 14%) with the pups removal. Thus, dopamine effectively inhibited PRL secretion during the later lactational stage, but could not do so during the earlier stage when there were mechanisms other than dopamine stimulating PRL secretion. Following luteal regression induced by CB-154, ovulation did not occur if the rats were treated with CB-154 on Day 10, whereas 50% of the rats ovulated within 4 days if treated on Day 13. Furthermore, in the lactating rats treated with anti-luteinizing hormone-releasing hormone serum during late pregnancy, ovulation was not observed until Day 10 of lactation. Since the serum progesterone levels were low in these rats due to the absence of ovulation and lactational corpora lutea, the blockade of ovulation was not due to elevated circulating progesterone during the early lactational period. The mechanism of ovulation blockade during lactation thus seems to shift from being progesterone independent to progesterone dependent at a similar period when the neuroendocrine control of PRL secretion shifts from dopamine independent to dependent.     

Serum prolactin concentrations and the initiation of maternal behavior in the rat

Maternal behavior and serum prolactin were measured in pregnant and virgin female rats. Pregnant rats were either ovariectomized or shamovariectomized on Day 17 of pregnancy, while virgin females were ovariectomized at the same age. Two days after surgery nests were rated and the three treatment groups were tested for responsiveness to rat pups. Both pregnant treatment groups built superior nests compared to the virgin group and also responded more frequently to rat pups within a 1 hr test period than the virgin controls. In addition, significantly more ovariectomized pregnant subjects responded to pups than did intact pregnant females. Serum prolactin levels did not differ among the three treatments nor did exposure to pups affect serum prolactin levels. In each treatment group serum prolactin was less than 15 ng/ml, well below the 139.7 ng/ml mean found on Day 23 of pregnancy. These data suggest that high levels of serum prolactin during late pregnancy are not essential for the initiation of maternal behavior in the rat.     

Growth and development of brain of artificially reared hypoketonemic rat pups

Three groups of rats were reared: mother-reared controls; artificially reared controls (AR-c), which were fed a milk substitute with the same composition of macro-nutrients as natural rat's milk; and an artificially reared test group (AR-h), which was fed a milk substitute identical to that fed AR-c pups except that the component of fat containing medium chain length fatty acids was omitted (medium chain triglyceride deficient) and replaced on an isocaloric basis with carbohydrate. The AR rats were fed the milk substitute from postnatal Day 5 until Day 17 by fitting them with gastric cannulas through which the milk could be infused automatically. The nutritional impact of the milk substitutes on growth and the integrity of the brain was assessed by a comparison of morphologic and biochemical markers. Pups in the AR-h group were hypoketonemic. Animals in all groups attained the same body weight by Day 17 and there was no difference in the morphologic markers among the groups with one exception: the vibrissal "barrel fields" of the somatosensory cortex of rat pups in both AR groups were reduced in size but not in number of distribution from those of the mother-reared groups. Furthermore, the brains of the rat pups in the AR groups were not different in weight, but they weighed less than brains of mother-reared controls. Our data show that although there are many similarities in the status of AR rat pups when compared with mother-reared controls, distinctive differences associated with artificial rearing are evident. We conclude that medium chain fatty acids in milk fat and the circulating ketone bodies are not mandatory substrates for growth and the development of the brain. Mechanisms must exist whereby alternative substrates are used to compensate when these metabolites are diminished in supply.     

Sensory stimuli from pups involved in inhibition of milk secretion in rats during late lactation

Lactating rats of two strains, Holtzman and Sprague-Dawley-Rolfsmeyer, were removed from the animal room on postpartum Day 20 and were placed in a testing room where there were no other rats. Milk secretion was stimulated in mothers of each strain 24 hr later in response to 30 min of exposure to a rack of lactators and their pups, placed 3 ft in front of the test mothers; this stimulation to milk secretion was prevented, provided their own pups were placed under, but not when they were placed alongside, the mothers 3–4 min beforehand. The milk secretion responses on the whole were quantitatively less in the Holtzman rats. The sensory signals emanating from the pups which were responsible for the inhibitory effect upon milk secretion were analyzed in Holtzman rats. Sound and odor each proved to be inhibitory; sight, however, was not. The function of the exteroceptive inhibition of milk secretion in the control of milk secretion in late lactation is discussed.     

Implantation delay and anti-deciduogenic activity in the rat by the anti-androgen, hydroxyflutamide

Studies were undertaken to determine whether the anti-androgen, hydroxyflutamide, has anti-progestagenic activity by using implantation, maintenance of pregnancy, and decidualization as end points. Prepubertal rats were induced to ovulate with the injection of 4 IU pregnant mare's serum gonadotropin and allowed to mate. Mated females were assigned randomly to various treatment groups. Beginning at 0800 h on Day 4 of pregnancy and at 12-h intervals thereafter, rats received a series of 6 s.c. injections of 5 mg hydroxyflutamide in oil, or oil only. Localized changes in endometrial vascular permeability, indicative of implantation, were assessed on Days 6 and 8 of pregnancy, after an injection of Evans blue dye. By Day 6, implantation has been initiated in the vehicle-treated rats, but not in hydroxyflutamide-treated rats. Hydroxyflutamide treatment was terminated on Day 6, and implantation was initiated by Day 8. The weights of uterine dye sites in hydroxyflutamide-treated rats on Day 8 were similar to those in vehicle-treated rats on Day 6. The number of fetuses and placentae were similar in all groups on Day 19. The weights of fetuses in both hydroxyflutamide-treated and hydroxyflutamide + progesterone-treated rats were similar and significantly lower than those in control rats. Although there were no significant differences between vehicle-treated or hydroxyflutamide-treated rats in the proportion of rats delivering and litter size, the hydroxyflutamide-treated rats delivered pups a mean of one day later than did the controls. Endometrial decidualization in ovariectomized, steroid-treated rats, following artificial stimuli, was significantly suppressed in hydroxyflutamide-treated rats compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sexual differentiation of the luteinizing hormone response of neonatal rats to the narcotic antagonist naloxone: critical role of estrogen receptors

Administration of the narcotic antagonist naloxone results in an elevation of serum luteinizing hormone (LH) levels in 10-day-old female, but not male, rats. Previous studies from this laboratory indicated a role for neonatal gonadal steroids in the development of this sex-specific response. In this study, the estrogen receptor antagonist OH-Tamoxifen or the androgen-receptor antagonist flutamide were injected on Days 1 or 9 of life, and the LH responses of male and female pups to naloxone were assessed on Day 10. Flutamide did not produce a response different from that seen in vehicle-treated pups, discounting a role for androgen receptors. OH-Tamoxifen on Day 9 caused an increase in basal levels of LH; neither sex showed a response to naloxone. However, OH-Tamoxifen treatment of 1-day-old males resulted in an enhanced release of LH upon challenge with naloxone on Day 10 of life; similar treatment of 1-day-old females resulted in a normal female-type response to the opioid antagonist. These results show that blockade of estrogen receptors in males during the "critical period" of sexual differentiation results in a female phenotypic response to naloxone. Therefore, estrogen receptors play a critical role in the sexual differentiation of the LH response to naloxone in neonatal male rats.     

Food restricting young hamsters (Mesocricetus auratus) affects sex ratio and growth of subsequent offspring

Trivers and Willard (1973) predicted that stressed adult female mammals may enhance their fitness by skewing offspring sex ratios and maternal investment to favor daughters. The present study investigated whether stressing young hamsters might also influence sex ratio and growth of subsequent offspring. Control females received food ad libitum (A) on Days 1-50 postpartum (AA). Experimental females were food-restricted (R) either on Days 1-25 (RA), Days 26-50 (AR), or Days 1-50 (RR) postpartum. Subjects were mated when 91-95 days old. Litter sizes and survivorship (= % litters within a treatment that contained at least one pup), sex ratio (= % males), and pup weights in the next generation were recorded every fifth day from parturition until Day 25 postpartum. Control litters contained significantly more offspring at birth than did RR litters. Sex ratio was significantly higher at birth for AA litters than for the other treatments. Postpartum sex ratio within each group remained similar to that recorded at birth. RR litters contained significantly fewer pups compared to the other three treatments from Days 5-25. RR female pups weighed significantly more at birth than their counterparts in the other treatments. Weights of males at birth were similar in all treatments. By Day 25, both male and female RR pups weighed significantly less than control, AR, and RA pups. Food restriction early in life may have long-term consequences on sex ratio and pup growth in golden hamsters.     

Effects of the intensity of the suckling stimulus and ovarian steroids on pituitary gonadotropin-releasing hormone receptors during lactation

These studies examined whether the decrease in pituitary responsiveness to gonadotropin-releasing hormone (GnRH) observed during lactation in the rat results from a change in pituitary GnRH receptors. GnRH binding capacity was determined by saturation analysis using D-Ala6 as both ligand and tracer. During the estrous cycle, the number of GnRH binding sites increased from 199 +/- 38 fmol/mg protein on estrus to 527 +/- 31 fmol/mg protein on the morning of proestrus, whereas there was no change in receptor affinity (Ka, 6-10 X 10(9) M-1), During lactation, females nursing 8 pups on Days 5 or 10 postpartum had 50% fewer GnRH receptors (109-120 fmol/mg protein) than observed during estrus or diestrus 1 (199-242 fmol/mg protein) although receptor affinity was similar among all the groups. No deficits in pituitary GnRH receptors were observed in females nursing 2 pups on Day 10 postpartum. Removal of the 8-pup suckling stimulus for 24 or 48 h resulted in a dramatic increase in GnRH receptor capacity by 24 h from 120 +/- 16 to 355 +/- 39 fmol/mg protein. The rise in GnRH receptors after pup removal was accompanied by an increase in serum luteinizing hormone (LH) and estradiol concentrations. To assess the role of ovarian steroids in determining GnRH receptor capacity during lactation, females were ovariectomized (OVX) on Day 2 postpartum. Suckling of a large litter (8 pups) completely blocked the postcastration rise in serum LH and in pituitary GnRH receptors on Day 10 postpartum (OVX+ 8, 77 +/- 12 fmol/mg protein; OVX+ 0, 442 +/- 38 fmol/mg protein).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of maternal marginal zinc deficiency on myelin protein profiles in the suckling rat and infant rhesus monkey

In the current study, the effects of marginal Zn deficiency on myelin protein profiles in neonatal rats and rhesus monkeys were investigated. Following mating, rats were fed a Zn-adequate diet,ad libitum (50 μg Zn/g; 50 Zn AL), or a marginal Zn diet (10 μg Zn/g) from day 0 (10 Zn d0) or day 14 (10 Zn d14) of gestation to day 20 postnatal. An additional group of dams was restricted-fed the control diet to the food intake of the 10 Zn d0 group (50 Zn RF). Day 20 pup plasma and liver Zn concentrations in the 10 Zn groups were lower than in the 50 Zn groups. In a parallel experiment, rhesus monkeys were fed a Zn-adequatead libitum diet (100 μg Zn/g) or a marginal Zn diet (4 μg Zn/g diet; MZD) throughout gestation and lactation. Day 30 monkey infant plasma and liver Zn levels were similar in the MZD and control groups. Rat brain and monkey brain cortex weights were similar among the dietary groups. The amount of myelin recovered (mg protein/g brain) from day 20 rat pups from the 10 Zn groups was lower than that recovered from the 50 Zn rat pups. Myelin recovery from the MZD and control monkey infants was similar. When myelin protein profiles were characterized, it was found that the percentages of high-molecular-weight (HMW) proteins and Wolfgram protein were higher, whereas the percentages of small and large basic proteins were lower in myelin from the 10 Zn d0 and 50 Zn RF pups compared to the distribution in the 50 Zn AL rat pups. Results for the 10 Zn d0 and 10 Zn d14 pups were similar for all of the parameters studied. The percentage of HMW proteins was higher and that of basic protein lower in myelin from MZD monkey infants compared to the percentage of these proteins in myelin from controls. Although the interpretation of the rat data is complicated because of the anorexia associated with the Zn deficiency, the observed changes in monkey myelin protein profiles provide strong evidence that maternal Zn deficiency affects myelination in the offspring.     

The induction of parturition in the bitch using sodium cloprostenol

The objectives of this studies were to determine a continuous low-dose treatment regimen for the administration of sodium cloprostenol to the bitch that did not cause polydipsia, and whether this treatment would induce normal and timed parturition in bitches during late pregnancy. Non-pregnant greyhound bitches (n=18) received sodium cloprostenol subcutaneously, via a miniosmotic pump, at dose rates of 0.875 to 4.5 microg/kg/24 h, for 7 days (Days 0 to 7). Daily water intake was measured from Day -2 to Day 9. Polydipsia was observed in bitches treated with the higher dose rates but not in bitches treated with the lowest dose rate of 0.875 microg/kg/24 h. In the second experiment, pregnant greyhound bitches received sodium cloprostenol at dose rates of 1 (n=4), 2 (n=1) and 3 microg/kg/24 h (n=1), on Day 57 of pregnancy. Polydipsia was observed in bitches treated at the higher dose rates of 2 and 3 microg/kg/24 h, but not in the bitches treated at the lower dose rate of 1 microg/kg/24 h. These treatments resulted in the successful induction of parturition. Parturition was associated with a decrease in plasma progesterone concentrations, a reduction in body temperature, and an increase in plasma concentrations of 13,14-dihydro-15-keto prostaglandin F2alpha. The first puppy was born 37.7 +/- 2.9 h after the start of treatment (range 28 to 46 h). The duration of whelping was approximately 15.7 +/- 2.2 h (range 10 to 24 h). The litter size was 9.2 +/- 0.8 pups (range 6 to 12 pups), and the puppy survival rate was 6.0 +/- 0.8 per litter (range 4 to 9 pups). This study demonstrated that the administration of sodium cloprostenol in continuous low dose for 24 h is an effective treatment for the induction of parturition in bitches during late pregnancy. This treatment resulted in the birth of healthy pups, with minimal or no side effects to the bitch.