Serum thyroid hormones and performance of offspring in ewes receiving propylthiouracil with or without melatonin

Two experiments were conducted during mid-gestation to examine effects in ewes of propylthiouracil (PTU) treatment alone or with melatonin on serum thyroid hormones, postpartum reproduction, and lamb performance. In the first experiment, beginning on day 0 (first day of treatment when all animals were 72.2+/-0.9 days of gestation), ewes received daily treatments (gavage) consisting of either 0mg (n=6) or 40 mg (n=6) PTU/kg body weight/day for 15 days. After 15 days, the 40 mg dosage was decreased to 20mg/kg body weight for an additional 20 days (35 days of PTU). Serum thyroxine (T4) did not differ (P>0.10) between groups through day 4; but on day 5, control females had a serum value of 67 ng/ml compared with 46 (+/-5)ng/ml for PTU-treated ewes (P=0.02). On the last day that 40 mg of PTU was administered, serum T4 averaged 67 and 7 (+/-5)ng/ml (P<0.001) in the two respective groups. Serum T4 remained low and was 80 and 1 ng/ml (P<0.001) in control and treated ewes on day 34. Serum T4 rose gradually after PTU but remained different from that observed in control ewes through day 48. Lambs from control and treated ewes had similar (P=0.46) T4 values at birth but lambs from PTU-treated ewes had lower (P=0.03) birth weights than did those from control ewes. Serum progesterone (P4) after parturition indicated a lack of cyclicity in all ewes. In the second experiment, beginning on day 0 (76.8+/-4.7 days of gestation), ewes received PTU as in Experiment 1. In addition, after 15 days of PTU, melatonin was given (i.m. injections at 5mg/day) for 30 days. Propylthiouracil decreased (P0.60) for lambs born to control and treated ewes. Female offspring of PTU+melatonin-treated dams reached puberty, became anestrus, and returned to cyclicity at similar (P>0.10) times to contemporary ewe lambs. Results indicate that 40/20mg PTU alone or with melatonin does not induce cyclicity after lambing in spring lambing ewes and has little effect on offspring performance.     

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.     

In utero exposure of mice to diethylstilbestrol alters neonatal ovarian follicle growth and development

The prenatal exposure of mice to diethylstilbestrol (DES, 10 micrograms/kg on day 15 of gestation) caused both quantitative and structural alterations in ovarian follicles within the neonatal ovary. At birth, control ovaries consisted of small type 1 and 2 ovarian follicles located in the ovarian cortex. By postnatal day 7, ovarian follicle development had advanced to the type 4 stage with larger follicles located within the ovarian medulla. In DES-exposed animals, ovarian follicle maturation was advanced with type 3b and 4 follicles appearing 24 h prior to their appearance in control animals. Also, type 5 ovarian follicles were present on postnatal day 6 in experimental animals but were never seen in control animals. In addition to an alteration in ovarian follicle dynamics, the diameter of individual ovarian follicles was transit time between the various stages of follicular development which results in a greater number of developmentally advanced ovarian follicles being present during neonatal ovarian development. The mechanism by which prenatal exposure to DES alters ovarian follicle dynamics during neonatal development is not known.     

Comparative Effects of Ethanol and Malnutrition on the Development of Catecholamine Neurons: Changes in Neurotransmitter Levels

Abstract: The comparative effects of exposure to ethanol and malnutrition on the concentrations of tyrosine and catecholamines in whole brain and selected regions of brain have been studied in the developing rat. These animals were the offspring of optimally nourished rats (control pups), of rats fed a diet with 35% of the calories supplied by ethanol (ETOH pups), or of animals fed a diet calorically equivalent to the latter but lacking ethanol (iso-caloric, 1C pups). These diets were administered to dams either during the last week of gestation (prenatal) or during lactation (postnatal). Tyrosine levels were elevated prior to birth in the prenatal ETOH or IC pups or at 1 and 2 weeks of age in postnatal ETOH or 1C pups as compared with values found in the control offspring. Dopamine concentration in whole brain was significantly lower in prenatal ETOH pups than in prenatal IC pups at 3 weeks of age. Levels in the brains of postnatal ETOH pups were lower than control values, but not relative to animals exposed to 1C diet. Investigation of corpus striatum showed a significant decrease in dopamine concentration compared with control or IC pup values as a result of postnatal exposure to ethanol. Norepinephrine levels in the whole brain of prenatal ETOH pups were consistently 30–40% lower than either control or matched 1C pups during development. At 3 weeks of age, the norepinephrine levels in the hypothalamus of animals exposed to ethanol pre or postnatally were 30–60% lower than values in the corresponding region in either control or 1C pups. In the rat model described, ethanol caused a decrease in catecholamine levels, perhaps solely by affecting the norepinephrine neurons.     

Suckling ability and maternal prolactin levels in hypothyroid rats

Long-Evans rats and their offspring were made hypothyroid by addition of the antithyroid goitrogen 6-N-propylthiouracil (PTU) to the drinking water (0.1%) from the day of parturition. Serum concentrations of prolactin (PRL), thyroid-stimulating hormone (TSH) and thyroxine (T4) were determined by double radioimmunoassay (RIA). From the fifth postnatal day, body weight of PTU-treated pups was significantly lower than that of control rats, and a strikingly elevated serum TSH level and nondetectable amount of T4 were measured both in PTU-exposed mothers and their offspring at Day 10 postpartum. To test the youngs' suckling capability and the amount of maternal milk production, 10- and 15-day-old normal and PTU-treated pups were separated from their mothers for 4 hr in the morning and then reunited and allowed to suckle. Normal pups gained body weight at the end of both the first and second hour postreunion, while PTU pups gained only during the first hour and lost weight in the second hour of testing. When the pups were exchanged between normal and PTU mothers, opposite results were obtained, indicating that the reduced gain in hypothyroid rats was not due to impaired suckling capability, or insufficient sensory stimulation for milk secretion but to a decreased milk production of PTU mothers. In accordance with this, in lactating hypothyroid rats both the basal (presuckling) level and the suckling-induced rise of serum PRL were found significantly depressed.     

Effects of cobalt on postnatal development and late gestation in rats upon oral administration

Four groups of pregnant Wistar rats, each of which consisted of 15 animals were administered 0, 12, 14 and 48 mg/kg/day of cobalt (II) chloride from the 14th day of gestation through 21 days of lactation. The offspring were observed for mortality, body weight, body and tail length and general symptomatology after 1, 4 and 21 days of nursing. The number of litters was higher for the control group. The survival ratios were also higher for the control group. Besides, a dose-dependent delay in the growth of the living young could be observed. No significant differences in organ weights in the animals killed 21 days after birth were observed. The blood parameters analysed did not show differences between the treated and control pups. Cobalt produced toxic effects on the mothers, affecting the late gestation as well as the postnatal development of the pups.     

Taste aversion learning in preweanling rats exposed to alcohol prenatally

The effects of prenatal alcohol exposure on the development of a conditioned taste aversion were examined in preweanling rat pups. Mothers of these pups were fed isocaloric liquid diets containing either 35 or 0% ethanol-derived calories (EDC) from gestation days 6 through 20. A pair-feeding procedure was employed, and an ad lib lab chow control group was also included. At 5, 10, or 15 days of age, pups were infused with a saccharin solution through a cannula implanted in the oral cavity. Half of the pups in each group were then injected with lithium chloride (LiCl), which served as the poisoning agent, and the other half with sodium chloride (NaCl) as a control. Animals were subsequently tested for a conditioned aversion to the saccharin solution. At 15 days of age, all of the pups in the LiCl-poisoned group demonstrated a conditioned taste aversion to the saccharin solution, but the degree of this aversion was less in alcohol-exposed offspring. At 10 days of age, a taste aversion was learned, although it was not as strong as that shown by 15-day-old pups, and it appeared to be learned equally well by all of the prenatal treatment groups. At 5 days of age, there was marginal support for taste aversion learning. Again, it did not interact with prenatal treatment. The ontogenic differences in taste aversion learning exhibited by alcohol-exposed offspring relative to controls are discussed in terms of altered hippocampal development.     

Effect of progesterone administration on the ovarian response to superovulatory treatments in cattle

To evaluate ovarian response in Angus cows previously treated with progesterone (P4), animals were randomly assigned to two groups: T600 group (n=14), 600 mg of P4/day. P4 was injected from days 3 to 7 of the estrous cycle. On day 7, superovulatory treatments began. The control group (n=12) was given vehicle only. The superovulatory treatments in the control group began on days 7-9 of the estrous cycle. The superovulatory total treatment dose of 400mg NIH FSH P1 was given twice a day over a 4-day period. Ultrasonography of the ovaries was conducted 3 days preceding the initiation of superovulatory treatment, every 24h. In both groups, an additional ultrasonographic evaluation was made at 24h after the end of superovulatory treatment. Blood samples were collected 4 days preceding the initiation of superovulatory treatment, every 24h. Additional samples were taken from the P600 group for 12 day after of initiation of superovulatory treatment every 24h, except on the fifth day after the initiation of superovulatory treatment. In the P600 group, P4 concentrations were greater than in the control group (P<0.01) and remained over 1 ng/ml up to day 11 after beginning of superovulatory treatment. The diameter of the dominant follicle was larger in the animals of the control group (P<0.01). Cows of the P600 group had a greater number of Class I (3-4mm) follicles (P<0.01). A significant day and treatment effect (P<0.01) were observed in Class II (5-9 mm) follicles. Effects due to treatment on the number of Class III follicles (P<0.05) were observed. In the P600 group, no estrous post-superovulatory was observed and there were no ovulations that occurred. Conversely, 100% of the cows of the control group showed estrous. In the P600 group, there were a greater number of Class III follicles (P<0.01) and a lesser number of Class II follicles (P<0.05) at 24h after the end of superovulatory. In the control group, 66.7% of the cows responded to superovulatory treatments. In conclusion, the daily administration of 600 mg of P4, from days 3 to 7 of the estrous cycle, produces an increase of plasma concentrations of this hormone from day 4, resulting in changes in follicular dynamics (absence of follicles greater than 10mm of diameter and an increase of the population of Class I follicles). As to the ovarian stimulation using Folltropin V in animals receiving a daily injection of 600 mg of P4 from days 3 to 7 of the estrous cycle, a greater population of follicles>or=10mm developed by 24h after superovulatory treatments were completed.     

Influences of prenatal and postnatal fraternity size on ovarian development in the mouse

An experiment was conducted to test effects of prenatal and postnatal fraternity size (size of litter in which an individual develops prenatally or is reared postnatally) on ovarian development in mice. Fraternity size treatments were created by standardizing sizes of prenatal and postnatal fraternities in which mice were gestated and reared. Prenatal fraternity size was standardized by surgery on Day 9 of gestation to 6, 10, and 14 fetuses. Postnatal fraternity size was standardized by randomly assigning pups to litters of 5, 10, or 15 pups within 24 h of birth. Female pups were killed at either 3 or 20 wk of age and right ovaries were prepared for histology. Follicles were classified by size and morphology, and numbers of follicles in each class were tabulated. Interaction of postnatal fraternity size and age was observed for number of antral follicles (p less than 0.05). Mice reared in small postnatal fraternities had more antral follicles at weaning (3 wk) and fewer antral follicles at maturity (20 wk of age) than mice reared in large postnatal fraternities. No effect of either prenatal or postnatal fraternity size on other follicle populations was observed (p greater than 0.20). Numbers of Type 2 (primordial), Type 3a, and Type 3b follicles changed with age (p less than 0.01); numbers of primordial follicles declined with age, but numbers of Type 3a and 3b follicles increased. A hypothesis of a negative association between postnatal fraternity size and number of antral follicles at 3 wk of age was supported, but a hypothesis of a positive association between fraternity size and number of primordial follicles was not supported.     

Perinatal methadone exposure and brain development: a biochemical study

Abstract— The neurochemical effect of maternally administered methadone (5 mg/kg, DL-methadone-HCI) on the brain (including the olfactory bulbs, cerebellum, and brain stem) and cerebellum of offspring exposed during gestation and/or lactation was studied in 10-, 21-, and 60-day old rats. Brain weights were significantly reduced in all methadone-exposed groups at 10 days of age, while only those rats subjected to methadone during gestation or lactation had deficits in brain weights at day 21; no differences were found at 60 days. Brain DNA content was significantly reduced in all opiate-exposed offspring at every age examined, but RNA/DNA and protein/DNA ratios were only consistently increased in rats of the gestation group. Cerebellar weight was reduced at 10 days in the gestation-lactation pups, at 21 days in rats of the gestation and lactation groups, and at 60 days in animals of the gestation and gestation-lactation groups. Cerebellar DNA content was significantly decreased in pups of the gestation group at every age investigated, but only reduced at 21 days in the lactation group and at 60 days in the gestation-lactation group. Rats in the lactation group had the greatest number of alterations in terms of RNA and protein, with the most noticeable being decreases in mean cellular RNA content on days 21 and 60 and a reduction in the mean cellular protein content on day 60. These data suggest that prenatal and/or postnatal methadone treatment affects the biochemical maturation of the central nervous system; deficits in neurons and/or glia, as well as a reduction in myelination, might be reflected in these changes.     

Two-year chronic bioassay study of rats exposed to a 1.6 GHz radiofrequency signal

The purpose of this study was to determine whether long-term exposure to a 1.6 GHz radiofrequency (RF) field would affect the incidence of cancer in Fischer 344 rats. Thirty-six timed-pregnant rats were randomly assigned to each of three treatment groups: two groups exposed to a far-field RF Iridium signal and a third group that was sham exposed. Exposures were chosen such that the brain SAR in the fetuses was 0.16 W/kg. Whole-body far-field exposures were initiated at 19 days of gestation and continued at 2 h/day, 7 days/week for dams and pups after parturition until weaning (approximately 23 days old). The offspring (700) of these dams were selected, 90 males and 90 females for each near-field treatment group, with SAR levels in the brain calculated to be as follows: (1) 1.6 W/kg, (2) 0.16 W/kg and (3) near-field sham controls, with an additional 80 males and 80 females as shelf controls. Confining, head-first, near-field exposures of 2 h/day, 5 days/week were initiated when the offspring were 36 +/- 1 days old and continued until the rats were 2 years old. No statistically significant differences were observed among treatment groups for number of live pups/litter, survival index, and weaning weights, nor were there differences in clinical signs or neoplastic lesions among the treatment groups. The percentages of animals surviving at the end of the near-field exposure were not different among the male groups. In females a significant decrease in survival time was observed for the cage control group.     

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.     

孕马血清促性腺激素对幼龄鼠卵巢和子宫发育的影响

目的探明孕马血清促性腺激素（PMSG）调控哺乳动物生殖生理机制。方法用4 IU PMSG分别处理出生第5天、第10天、第15天和第21天幼鼠,观察其对卵巢和子宫发育的影响。结果（1）PMSG处理后,出生第15天幼鼠的卵巢指数（33.08%）与对照组（27.16%）间差异显著（P〈0.05）;（2）PMSG处理后,第5天、10天和第15天幼鼠的初级卵泡和有腔卵泡相对数量与对照相比无差异,而21 d处理组次级卵泡相对数量显著增加;（3）虽然出生后10 d前的幼鼠子宫对PMSG的反应较弱,但是,PMSG对出生后15-21 d幼鼠子宫重量指数、子宫肌层和子宫内膜层厚度发育具有明显的促进作用,而对子宫腺体数量增加无影响。结论PMSG对幼鼠卵巢的发育无明显影响;PMSG对出生后第15天前后的子宫发挥作用,而且其作用随着出生日龄的增加而增强。     

Impact of chronic ethanol intake of rat mothers on the seizure susceptibility of their immature male offspring

The aim of present study was to examine the impact of prenatal ethanol exposure on seizure susceptibility of the offspring. Pregnant Wistar rats were compelled to drink either 10% or 20% ethanol solution, as the only drinking fluid since conception up to the weaning of their offspring at the age of 28 days. Pregnant and nursing rats of the control group drank water. Electrophysiological experiments (repeated electrical stimulation and analysis of cortical afterdischarges duration) were than performed on their immature offspring. Rat pups were tested on postnatal day 18, 25, and 35. Shortening of afterdischarges duration was observed in 18-day-old animals (mothers drank 20% ethanol) when compared with age matched controls and failure of post-ictal depression phenomenon was found in 25- and 35-day-old animals. Our findings signalize that ethanol exposure during pregnancy influences seizure susceptibility by acting on excitatory/inhibitory brain systems and this effect is dose- and age-dependent.     

Thyroid dependent maturation of β-adrenergic receptors in the rat lung

β-Adrenergic receptors were identified in membranes of fetal and postnatal rat lung with (?)-[³H]dihydroalprenolol, [³H]DHA. β-Receptor number (Bmax) increased 11-fold from day 18 of gestation to adult levels by day 28 of postnatal life. The increase of β-adrenergic receptors occurring between postnatal days 15 and 28 was dependent on thyroxine (T4) in propylthiouracil treated pups. β-Adrenergic receptors on day 28 were identical in euthyroid (PTU + T4) as compared to normal control pups (489±31 and 491±30 femtomoles·mg^?1) however receptors were markedly reduced in 28 day hypothyroid pups (PTU alone), Bmax = 294±21.5, m±S.E. p<0.01. Treatment of the hypothyroid pups with T4 for three days on postnatal day 25 increased β-adrenergic receptors approximately two-fold by day 28. This thyroid hormone dependent increase in lung β-adrenergic receptors occurs between postnatal days 15 and 28 coincident with the known increase in thyroid gland activity in the rat pup.     

Post-natal diet determines insulin resistance in fetally malnourished, low birthweight rats (F1) but diet does not modify the insulin resistance of their offspring (F2)

We examined the effects of prenatal and postnatal nutrition on birthweight and insulin sensitivity, indicated by the glucose/insulin (G/I) ratio, in adult rats (F1 generation) and in their adult offspring (F2 generation). Rat pups (F1) whose dams consumed low-protein diets during gestation (malnourished) consumed either nutritionally adequate (control) or high-fat diets ad libitum post-weaning. The offspring of these rats (F2) were maintained on the same diets as their respective dams. Separate pups (F1) whose dams consumed high-fat diets during gestation (over-nourished) were maintained on high-fat diets post-weaning, as were their offspring (F2). Birthweights were significantly reduced in all fetally malnourished F1 animals. At approximately 70 d of age, fasting insulin sensitivity in over-nourished F1 rats was significantly reduced compared to controls regardless of whether they were malnourished or over-nourished in utero; however, fetally malnourished F1 rats consuming control diets post-natally had significantly greater fasting insulin sensitivity than control animals. At 30 and 120 min post-glucose load, insulin sensitivity was reduced 12-65% in both groups of over-nourished F1 rats as compared to the fetally malnourished F1 rats consuming the control diet. Birthweights were significantly lower in F2 animals whose dams (F1) were fetally malnourished and weaned to high fat diets. Insulin sensitivity was significantly reduced in all F2 animals versus control animals, regardless of dietary treatment. Thus, post-natal diets alter insulin sensitivity in fetally malnourished, adult rats; and maternal malnutrition during gestation results in insulin resistance in offspring, irrespective of offsprings' birthweight or diet.     

Effects of prenatal dexamethasone on spatial learning and response to stress is influenced by maternal factors

The present study investigated the effect of prenatal dexamethasone (Dex) exposure on early perinatal events, hippocampal function, and response to stress. Pregnant rats received Dex in the evening water (2.5 microg/ml) or tap water (Veh) from gestational day 15 until delivery. On the day of parturition, pups were randomized, cross-fostered, and reduced to eight or nine per dam. Four groups resulted: Veh-Veh (offspring exposed to Veh in utero, rearing mother treated with Veh during gestation), Veh-Dex, Dex-Veh, and Dex-Dex. Spatial visual memory was evaluated with the Morris water maze. The corticosterone response to restraint stress was examined, and the expression of hippocampal glucocorticoid and mineralocorticoid receptors mRNA was determined by in situ hybridization. Exposure to Dex caused restlessness in mothers, low birth weights, and poor weight gain in the offspring. The Dex-Dex males had impaired spatial learning, inability to rapidly terminate the adrenocortical response to stress, and decreased hippocampal glucocorticoid receptor (GR) mRNA expression. In contrast, Dex-exposed animals reared by Veh-treated mothers had adequate spatial learning, enhanced glucocorticoid feedback, and increased hippocampal GR mRNA. We conclude that the environment provided by a healthy mother during the postnatal period can prevent the detrimental effects of prenatal Dex administration on cognition, GR mRNA expression of the hippocampus, and the quality of the stress response.     

The effect of late prenatal and/or early postnatal zinc deficiency on the development and some biochemical aspects of the cerebellum and hippocampus in rats

In rats, late prenatal and/or early postnatal zinc deficiency results in behavioural anomalies in adult animals, but not in overt dysmorphogenesis of the central nervous system. Cerebellar and hippocampal development occurs mainly in the first three weeks postnatally and zinc accumulates specifically in the mossy fibres of the hippocampus during this period.In the present investigation, rat pups were suckled by dams fed a zinc-deficient (<0.5 mg/kg) diet either from day 19 of pregnancy or from parturition. Control animals were restricted-fed the same diet supplemented with 100 mg zinc/kg. Studies were performed on pups either on day 18 postpartum in the case of animals fed the experimental diets from parturition, or on day 20 for pups which received treatment from day 19 of gestation.Cerebellar and hippocampal weights were lower in pups suckling from zinc-deficient dams but zinc levels were not affected in either organ, although histological evidence suggested less zinc in the hippocampal mossy fibres. Incorporation of H-thymidine into cerebellar and hippocampal DNA was not affected by maternal zinc status, nor was the activity of the zinc metalloenzyme alkaline phosphatase.The activity of the myelin-marker enzyme 2′, 3′-cyclic nucleotide 3′-phosphohydrolase was substantially lower in both regions of the brain in zinc deprived pups, especially in the hippocampus. Activity of the zinc metalloenzyme L-glutamic acid dehydrogenase was also diminished in both tissues from 20-day-old pups and in the hippocampi of 18-day-old animals.The data suggest that cerebellar and hippocampal DNA synthesis is not seriously affected by late prenatal and/or early postnatal zinc depletion, but that the activities of two enzymes associated with neural function are. The possibility is raised that these defects may be associated with the behavioural changes observed in rats subjected to zinc impoverishment during the period of maximal cerebellar and the hippocampal development.     

Prenatal exposure to antiandrogen flutamide affects androgen receptor (AR) expression in postnatal ovarian development in pig

The following study was undertaken to localize androgen receptors (ARs) in various structures of the porcine ovary after prenatal exposure to antiandrogen flutamide. In utero treatment by antiandrogens may have adverse effects on reproductive function in immature and adult animals. Flutamide was injected into pregnant swines between days 20 and 28 (GD20) or 80 to 88 (GD80) of gestation. The ovaries were collected from treated animals and from control ones (non-treated) at two different points of development: from immature and adult pigs. Immunoexpression of AR was determined for preantral and antral follicles and for stroma cells. Immunostaining showed that AR expression in immature animals was unaffected in the primary follicles, while in the preantral and antral follicles the AR level fluctuated depending on day of treatment as well as on analyzed tissue. In adult animals, the immunoexpression of AR slightly decreased in antral follicles independently on the day of flutamide treatment. Therefore, AR expression in postnatal life may be affected by in utero exposure to antiandrogen flutamide.     

Effect of vitamin E on follicular cell proliferation and expression of apoptosis-associated factors in rats with 6-N-propyl-2-thiouracil-induced goitrogenesis

We have investigated immunohistochemically the effect of dl-alpha-tocopherol (vitamin E) on thyroid gland with 6-n-propyl-2-thiouracil (PTU)-induced hypothyroidism in rats. The animals were divided into four groups. Rats in group I were designated as control, rats in group II were treated with injections of PTU (10 mg/kg) for 15 days, rats in group III were treated with injections of PTU+vitamin E (10 mg/100 g) for 15 days. Rats in group IV were treated with injections PTU for 15 days and kept for 15 next days after cessation of PTU treatment. At the end of experiment, the animals were killed by decapitation, blood samples were obtained, thyroid tissues were collected and processed for quantitative evaluation of immunohistochemical PCNA (marker of cell proliferation), Bax (pro-apoptotic marker) and Bcl-2 (anti-apoptotic marker) staining. There was an increase in the number of PCNA-immunopositive cells in follicular epithelial cells of group II rats compared with other groups (p<0.05). After vitamin E treatment, the number of PCNA-immunopositive cells decreased (p<0.05) while the number of Bax-immunopositive cells increased (p<0.05). The number of Bcl-2-positive follicular epithelial cells of group IV rats was higher than in those of other groups (p<0.05). The results of this study indicate that hypothyroidism induces cell proliferation in the thyroid gland and vitamin E may promote involution of the gland.