Studies on the role of zinc in parturition in the rat.

1. Pregnant rats were fed either low (less than 1 p.p.m.) Zn or control (40 p.p.m. Zn) diets from day 10 of gestation. They were killed at intervals during the last 96 h preceding the normal time for onset of parturition, and differences in plasma progesterone, oestradiol-17 beta and ovarian 20 alpha-hydroxysteroid dehydrogenase were assessed. 2. Gestation was prolonged in Zn-deficient rats. 3. Although the preparturient decline in plasma progesterone began at the same time in all groups, at term, plasma progesterone concentration in Zn-deficient rats remained significantly higher than in normal females. 4. Induction of ovarian 20 alpha-hydroxysteroid dehydrogenase activity was delayed by about 8 h by Zn deficiency. This delay was not observed if prostaglandin F2 alpha was injected previously. 5. The results suggest a Zn-dependent step(s) in uterine synthesis and/or release of prostanoids.     

Dietary zinc deficiency has no effect on auditory brainstem responses in the rat

Zinc has been shown to effect--in vitro--a number of processes associated with neurotransmission. We have tested whether the rate of impulse conduction--in vivo--as measured from the latencies of auditory brainstem responses (ABR), is influenced by dietary zinc deficiency in the rat. Dietary zinc deficiency for up to 26 wk had no effect on the wave I-IV interval compared to zinc-adequate fed animals. The results are discussed in relation to the observed constancy of brain overall and extracellular fluid zinc concentrations under conditions of dietary zinc deficiency.     

Dietary phytate,zinc and hidden zinc deficiency

Epidemiological data suggest at least one in five humans are at risk of zinc deficiency. This is in large part because the phytate in cereals and legumes has not been removed during food preparation. Phytate, a potent indigestible ligand for zinc prevents it's absorption. Without knowledge of the frequency of consumption of foods rich in phytate, and foods rich in bioavailable zinc, the recognition of zinc deficiency early in the illness may be difficult. Plasma zinc is insensitive to early zinc deficiency. Serum ferritin concentration ≤ 20 μg/L is a potential indirect biomarker. Early effects of zinc deficiency are chemical, functional and may be “hidden”. The clinical problem is illustrated by 2 studies that involved US Mexican-American children, and US premenopausal women. The children were consuming home diets that included traditional foods high in phytate. The premenopausal women were not eating red meat on a regular basis, and their consumption of phytate was mainly from bran breakfast cereals. In both studies the presence of zinc deficiency was proven by functional responses to controlled zinc treatment. In the children lean-mass, reasoning, and immunity were significantly affected. In the women memory, reasoning, and eye-hand coordination were significantly affected. A screening self-administered food frequency questionnaire for office might help caregiver's identify patients at risk of zinc deficiency.     

Dietary zinc intake,supplemental zinc intake and serum zinc levels and the prevalence of kidney stones in adults

ObjectiveThe association between zinc intake and the risk of kidney stones remains controversial. We examined the associations between dietary zinc intake, supplemental zinc intake and serum zinc levels and the prevalence of kidney stones in adults.MethodsAdult participants from the 2007–2016 NHANES were included. Restricted cubic splines were adopted to assess the dose-response relationships.ResultsDietary zinc intake was linearly associated with the prevalence of kidney stones (P_{for non-linearity} = 0.50), and the odds ratios (95% confidence intervals) of kidney stones were 0.75 (0.51–1.04) for 10 mg/day, 0.65 (0.39-0.97) for 20 mg/day, 0.53 (0.30-0.94) for 30 mg/day and 0.45 (0.22-0.95) for 40 mg/day. The linear relationship was also observed among women and overweight/obese individuals. No association was found between supplemental zinc intake and the prevalence of kidney stones. A non-linear relationship was found between serum zinc levels and the prevalence of kidney stones (P_{for non-linearity} = 0.02), and the odds ratios (95% confidence intervals) of kidney stones were 0.52 (0.33-0.82) for 70 ug/dL, 0.43 (0.24-0.77) for 90 ug/dL, 0.56 (0.32-0.98) for 110 ug/dL and 0.77 (0.37–1.62) for 130 ug/dL. The non-linear relationship was also observed among men and overweight/obese individuals.ConclusionsDietary zinc intake and serum zinc levels were inversely associated with the prevalence of kidney stones in adults, and there may be effect modification by participant sex and body mass index. The present analysis is limited in its ability to establish causality.     

Myometrial oxytocin receptors and prostaglandin in the parturition process in the rat.

Parturition in rats is associated with an abrupt and marked increase in myometrial oxytocin (OT) receptor concentrations. In this study, we investigated the role of myometrial OT receptors in the initiation and the process of parturition. We produced chronic OT receptor blockade during the last 3 days of gestation by administration of a specific OT antagonist at 100 micrograms/day and 300 micrograms/day. We also suppressed OT receptor formation by inhibiting prostaglandin synthesis with naproxen sodium at 2 mg/day and 5 mg/day. We found that chronic blockade of OT receptors inhibited the uterotonic response to OT in Day 22 and Day 23 pregnant rats in a dose-dependent manner. OT antagonist treatment did not prolong the gestation period. However, the duration of parturition, fetal mortality, and the mortality incidence were increased in rats treated with the high dose of the OT antagonist compared to controls. Naproxen sodium at both dosage levels prolonged gestation by 24 h or longer, doubled the duration of parturition, and markedly increased fetal mortality and mortality incidence. Combined OT antagonist and naproxen treatment produced adverse outcomes similar to that produced by naproxen treatment alone. Myometrial OT receptor concentrations were markedly increased in all rats immediately postpartum, ranging from 210 to 425 fmol/mg protein compared to the 50 to 100 fmol/mg found in Day 21 and Day 22 pregnant rats. Correlation analyses between OT receptor concentrations and various parameters associated with gestation and parturition showed that there was a correlation between low OT receptor concentrations and long gestation period, prolonged parturition, and high fetal mortality rate.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dietary subacute zinc deficiency and potassium metabolism

In a controlled animal experiment the effects of dietary subacute Zn deficiency on growth, Zn concentration, and tissue 42-K distribution were studied. Growth retardation caused lower body weight because both skeletal and heart muscle showed a reduction in cell mass. Zn concentrations were reduced in most tissues, however, they remained unaltered in heart muscle. 42-K activity increased in skeletal muscle and pancreas. We hypothesize the latter reflects the organs rate of metabolism, inducing the exocrine pancreas to increase Zn absorption; in skeletal muscle it may induce also alterations in cell potentiation, causing restless behavior. As suggested by the calculated specific K activity (Bq/mol), the K uptake was highest in liver and bone, high in pancreas and skeletal muscle and low in heart muscle. The latter suggests K retention in heart muscle. Specific activity in plasma and jejunum remained unaltered: K status and absorption seem unaffected. Zn deficiency causes different 42-K activities in the various tissues, that respond by alterations in K metabolism without the induction of K deficiency.     

Lactogenesis in the rat. Changes in metabolic parameters at parturition

1. Tissue concentrations of nucleic acids, protein, fat, water, metabolites and lactose, and the activities of seven enzymes concerned in milk biosynthesis, were measured in the rat mammary gland at closely spaced times before, at and after parturition. 2. Changes are seen in the tissue concentrations of most substances, and several changes are initiated at least during the day preceding parturition. 3. Lactose, which is absent 1 day before parturition, is found in amounts of 12μmoles/g. fresh wt. of tissue at parturition. 4. From the tissue activities before parturition of three enzymes on the biosynthetic pathway of lactose, and, from the small changes observed in their activities at parturition itself, it is concluded that the factors responsible for the appearance of lactose at parturition remain to be demonstrated.     

Effect of amniotic sac puncture on parturition in rat

Pregnant Charles Foster rats were subjected to amniotic sac puncture on day 15 of gestation and the effect was observed on parturition. All the control rats as expected delivered on day 22 of gestation. In the group where all the sacs were punctured, only 12.5% rats delivered on day 22 while rest either failed to deliver (62.5%) or died (25%). In the group with unpunctured sacs at vaginal ends, 75% rats delivered on day 21 while 25% on day 22. In the group with unpunctured sacs at ovarian ends, 75% rats delivered on day 23 and rest 25% failed to deliver. The resorption rates ranged between 61 to 94% in different groups. Malformations were observed only in one pup. The results suggest that amniotic sac puncture interferes with parturition in the form of either failure or delayed parturition. Nonpatency of the birth canal due to puncture induced fetal deaths and tissue adhesions were presumed to be the contributing factors.     

Evidence for a noradrenergic transmission in the control of parturition in the rat

6-Hydroxydopamine, when injected at 14:00 h on Days 21 and 22 of pregnancy in the rat (2 X 50 mg/kg), markedly decreased plasma and uterine noradrenaline concentrations (-60% and -82% respectively; P less than 0.001). As a consequence of this treatment, there was severe disturbance in the distribution pattern of parturitions: 61% of rats had suppressed parturition and 31% of rats displayed a lengthened or interrupted labour. A bolus dose of prazosin (3 mg/kg) administered at 12:00 h on Day 22 completely blocked the normal process of parturition throughout the next 6 h, a result which is compatible with the half-life of the drug (2.9 +/- 0.8 h). Administration of phentolamine (3 mg/kg) at term induced a significant decrease of uterine activity (frequency X duration of bursts of spike potentials) as revealed by electromyographic recordings in vivo. These results suggest that noradrenaline released from sympathetic nerve terminals interacts with alpha-adrenoceptors located post-synaptically to improve the overall excitability of the myometrium at the onset of labour.     

Dietary zinc modifies the characteristics of endothelial dilation in normozincemic rats

Because zinc attenuates endothelial cell dysfunction that proceeds atherosclerosis, depressed zinc status may be involved in the initiation of endothelial dysfunction. However, before recommending a zinc-enriched diet to reduce the risks for atherosclerosis, the effect of excess zinc on endothelial cell functions in normozincemic status should be known. Therefore, in this study, the effect of dietary zinc on normal endothelial cell functions in animals subjected to a diet containing 334 +/- 58 ppm zinc for 30 d was studied to see whether supplemented zinc has an effect on endothelial cells. Despite a slight increase in blood zinc, unaltered aortic and kidney zinc contents were associated with unchanged blood pressure in rats subjected to a zinc-enriched diet. Increased basal nitric oxide and prostacyclin were accompanied by a normal response to phenylephrine. Dietary zinc influenced neither endothelial-dependent nor endothelial-independent relaxations significantly. However, it elevated the share of M1-type cholinoceptor response as well as dilator prostaglandin release, which seems to be nitric oxide dependent. There was a strong correlation (r=0.826, p<0.05) between M1-type cholinoceptor response and prostacyclin release in zinc-treated rings. These results suggested that zinc ions increases M1-mediated prostacyclin release in normal endothelial cells without altering intracellular pathways.     

Dietary zinc restriction promotes degeneration of the endocrine pancreas in mice

Zinc is a key component of several proteins, interacting with the pancreatic hormones insulin and amylin. The role of zinc in insulin oligomerization and crystallinity is well established, although the effects of dietary zinc restriction on both energetic metabolism and β-pancreatic hormonemia and morphology remain unexplored. Here we report the effects of dietary zinc restriction on the endocrine pancreas and metabolic phenotype of mice. Nontransgenic male Swiss mice were fed a low-zinc or control diet for 4 weeks after weanling. Growth, glycemia, insulinemia and amylinemia were lower and pancreatic islets were smaller in the intervention group despite the preserved insulin crystallinity in secretory granules. We found strong immunostaining for insulin, amylin and oligomers in apoptotic pancreatic islet. High production of β-pancreatic hormones in zinc-restricted animals counteracted the reduced islet size caused by apoptosis. These data suggest that zinc deficiency is sufficient to promote islet β-cell hormonal disruption and degeneration.     

Diethylstilbestrol-induced perinatal lethality in the rat. II. Perturbation of parturition

Evidence is presented suggesting that the fetolethal properties of diethylstilbestrol (DES) are indirect, mediated maternally through a perturbation of the normal mechanisms of parturition. Oral administration of the compound to Sprague-Dawley rats near Day 18 of pregnancy was shown to delay the onset of parturition, prolong labor, and induce dystocia, with a concomitant large increase in perinatal mortality. Exposure during Days 8-16 was without effect, whereas treatment in the Day 18-20 interval resulted in preterm delivery. Inability to initiate labor at term, accompanied by fetal death, also resulted from the administration of hCG on Days 16-18. The relative incidence of stillbirths in DES-exposed pups was markedly decreased by Caesarean delivery. The average weight of the maternal pituitary gland was not affected by treatment, whereas maternal adrenal glands were 30% larger. Maternal blood levels of corticosterone were not significantly elevated, however. The average number of follicles on Day 21 was significantly reduced by DES, and a histological analysis failed to demonstrate a luteotropic effect of the compound. In dams treated on Days 8-18, serum progesterone was reduced by as much as 60%, and total estrogens were 32% lower than in controls. We conclude that DES acts in the rat to depress the preterm levels of steroid hormones, which leads to a failure of uterine contraction accompanied by placental detachment and fetal death.     

Timing of parturition in the rat: an analysis of successive births

To determine whether consecutive parturitions within individual rats are likely to occur around the same time of the 24h day, female rats mated prior to ovulation and maintained on a LD 12:12 photoperiod, were observed over either two or three parturitions. A subgroup of females was placed on constant light during the second gestation in order to determine the role of photoperiod in the temporal synchronization of consecutive births. The major findings were 1. individual females tended to give birth around the same time of the day on consecutive births so long as the photoperiod remained constant; 2. the small percentage of births occurring during darkness, the less-prevalent time of the photoperiod for birthing, were anomalous births for individual females; and 3. litter weight was a significant factor in predicting time of birth for females, but this effect interacted with photoperiod. These data elucidate the importance of knowing previous birth time, litter weight, and photoperiod on predicting the time of parturition in the rat.