Morphological and genetic characteristics of the open-eyelid mutant spontaneously occurring in NC-strain mice

A heritable open-eyelid mutant which arose spontaneously in the NC strain of mouse in 1982 has been maintained as the NC-eob line through brother-sister matings. When the line exceeded the 12th generation, its reproductive capabilities were initially compared with those of the NC strain. Then eye abnormalities were investigated morphologically and genetically. Although most of the reproductive parameters in the NC-eob line were comparable to those in the NC strain, a significant decrease was observed in the mean number of pups delivered, and the viability of pups at 7 days of age was reduced to 55%. The eyelids of pups were widely open at birth. The exposed cornea dried within a few hours and a bloody exudate appeared around the margin of the eyelids. At 1 day of age, the eye opening was smaller in size and covered with a scab. Histological examination demonstrated apparent inflammatory changes in the cornea and conjunctiva. At 21 days of age, the eyes revealed opacity, a rough surface, and microphthalmia. Histological findings in the cornea, such as keratosis and vascularization, coincided with the eye opacity. The weight and size of the eyeballs were almost the same as those in normal NC pups. However, a significant decrease in the length of the palpebral rima was evident and this was considered to be the cause of the microphthalmia. The results of genetic analysis indicated that these eye abnormalities were caused by an autosomal recessive gene, eob. These results suggested that the eob gene might be a new mutation manifesting semi-lethality as a pleiotropic effect.     

Effects of perinatal maternal food restriction on pituitary-gonadal axis and plasma leptin level in rat pup at birth and weaning and on timing of puberty

The effects of maternal 50% food restriction (FR) during the last week of gestation and/or lactation on pituitary-gonadal axis (at birth and weaning), on circulating levels of leptin (at weaning), and on the onset of puberty have been determined in rats at birth and at weaning. Maternal FR during pregnancy has no effect at term on the litter size, on the basal level of testosterone in male pups, and on the drastic surge of circulating testosterone that occurs 2 h after birth. At weaning, similar retardation of body growth is observed in male and female pups from mothers exposed to FR. This undernutrition induces the most drastic effects when it is performed during both gestation and lactation or during lactation alone. Drastic retardation of testicle growth with reduction of cross-sectional area and intratubular lumen of the seminiferous tubules is observed in male pups from mothers exposed to undernutrition during both gestation and lactation or during lactation alone. Maternal FR during the perinatal period reduces circulating levels of FSH in male pups without affecting LH and testosterone concentrations. Maternal FR does not affect circulating levels of LH, estradiol, and progesterone in female pups. Female pups from mothers exposed to FR during both gestation and lactation show a significant increase of plasma FSH as well as a drastic retardation of ovarian growth. The follicular population was also altered. The number of antral follicles of small size (vesicular follicles) was increased, although the number of antral follicles of large size (graafian follicles) was reduced. Maternal FR occurring during both late gestation and lactation (male and female pups), during lactation alone (male and female pups), or during late gestation (female pups) induces a drastic reduction of plasma leptin and fat mass in pups at weaning. The onset of puberty is delayed in pups of both sexes from mothers exposed to FR during lactation and during both gestation and lactation. In conclusion, these data demonstrate that a perinatal growth retardation induced by maternal FR has long-term consequences on both size and histology of the genitals, on plasma gonadotropins and leptin levels, on fat stores at weaning, and on the onset of puberty.     

Thyroxine-induced hyperthyroidism upon the reproductive performance of female rats.

L-Thyroxine (L-T4) was injected into mature rats daily at levels of 0, 3, 6, 12, 24, 48 and 96 mug/100 g body weight through estrous cycling, conception, pregnancy, parturition and 20 days of lactation. Mothers which lactated to 20 days were killed and mammary glands measured for DNA and RNA content. Those which were not able to maintain their pups were killed on the day when all pups died. Estrous cycling and pregnancy were not markedly effected by exogenous L-T4 at levels 3-96 times the normal thyroxine secretion rate in rats. After parturition the mothers on L-T4 above 12 mug did not allow the pups to suckle. As a result the pups died within 2-7 days after birth. Levels of L-T4 from 3 to 12 mug allowed lactation to progress, but survival of pups to day 20 of lactation was significantly lower than in the normal control group. The results of this study indicate that high levels of L-T4 inhibit mammary growth and mild secretion. This, in turn, results in the loss of pups, probably through depletion of prolactin as a result of higher metabolic rate due to hyperthyroidism.     

Mass changes of grey seal Halichoerus grypus pups on Sable Island: differential maternal investment reconsidered

Theory predicts that where variance in reproductive success differs between sexes, as in many sexually dimorphic species, mothers should invest more in male than in female offspring. In pinnipeds, parental investment is the sole responsibility of the mother. Both size at birth and subsequent mass gain during lactation are measures of that investment. We studied mass gain of grey seal pups, a sexually dimorphic species, during lactation and mass loss during the first 13 days of the postweaning fast using longitudinal data obtained on Sable Island, Canada. A mixed-effects repeated measures model was used to account for the serial correlation in these longitudinal data. We found no significant difference in the birth mass of male (16.6 ± 0.45 kg) and female (15.6 ±0.74 kg) pups. Rate of mass gain by males (3.0 ± 0.13 kg/d) and females (2.7 ± 0.12 kg/d) also did not differ significantly during the lactation period. Grey seal pups on Sable Island tended to be larger at birth and gain mass more rapidly (70%–100%) during lactation than those in the United Kingdom. Mass loss of weaned pups was curvilinear over time. Over the first 10 days of the fast, pups lost 22% of their weaning mass. In both males and females, large pups lost mass more slowly than small ones during the postweaning fast. Based on our results and a review of previous studies, we found little evidence of differential maternal investment in male and female grey seal pups.     

Leptin serum concentration,food intake and body weight in rats whose mothers were exposed to malnutrition during lactation

We had shown that adult animals, whose mothers were submitted to protein or energy restriction during lactation, differ from controls in their body weight and thyroid function. The aim of this study was to evaluate, from birth through six months of age, leptin serum concentration, body weight and food intake in animals whose mothers received protein or energy restricted-diet during lactation as follows: control (C)-23% protein; protein-restricted (PR)-8% protein; energy-restricted (ER)-23% protein, in restricted quantity, according to the mean ingestion of the PR group. After weaning (day 21) all pups had free access the control diet. Body weight of pups from PR mothers were always lower than those from controls (p < 0.05), while body weight of pups from ER mothers surpassed that of the C group significantly at 140 days of age. The food intake was lower in both offspring from PR and ER mothers, normalizing on the 32th day in pups from ER mothers and on the 52th day in pups from PR mothers. Leptin serum concentration in both offspring from PR and ER mothers were significantly decreased on the 12th day (p < 0.05) and increased on the 21st day (p < 0.05) compared to control. After weaning there was no differences among the groups. It is possible that changes in leptin concentration during lactation in the offspring of malnourished groups could permanently modify the setpoint for body weight control.     

Grey seal, Halichoerus grypus, energetics: females invest more in male offspring

Grey seal females transfer large amounts of energy to their pups during the brief lactation period. The costs of lactation have been measured using weight changes of mother and pup pairs. Large females come ashore to give birth earlier in the season and lose weight more rapidly than smaller females. The sex ratio of Grey seal pups born is skewed towards males in the early part of the breeding season. Male pups are larger at birth and gain weight more rapidly than female pups, and their mothers show a correspondingly faster rate of weight loss than mothers of female pups. The energy costs of gestation and lactation to a Grey seal mother are 31 GJ for male pups and2–8 GJ for female pups. Males are therefore 10% more costly in energy terms to raise to weaning. Because, on average, large females arrive at breeding sites before smaller animals, biased results on weight changes would be obtained from methods which do not use repeated weighings. We suggest that the high efficiencies of lactation estimated for Harp seals compared with other phocid seals could be accounted for by such a bias.     

树实验种群的繁育

探讨了树实验种群的繁育。结果是5对成年树在7个月内共产11窝31只仔树。27只出生后即人工喂养的仔树中,25只健康存活至进入动物实验。成年树平均产仔周期为（52±8.9）d;仔树的人工喂养成活率为92.6%。可以认为树实验种群的人工繁育是可行的。人工繁育的树有望取代野外捕获的树用于有关的动物实验研究。     

High liver lipoprotein lipase activity in hyperlipemic developing rats from undernourished pregnant mothers

To study the potential relationship between circulating triacylglycerol (TAG) levels and lipoprotein lipase (LPL) activity in the newborn rat liver, pups from undernourished or normal control mothers were nursed by normal dams, and studied at 0, 1, 15 or 30 days of age. Plasma TAG levels and liver TAG concentration increased more in pups from undernourished mothers than they did in controls. At birth, liver LPL activity was similarly high in both groups but, whereas in controls it decreased progressively after birth, in pups from undernourished mothers it remained stable until 15 days of age. Results suggest that the hypertriglyceridemia present in pups from undernourished mothers may be responsible for the sustained high LPL activity in their liver which may enhance the hepatic uptake of circulating TAG.     

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)     

Effects of mandibular gland ectomy and environmental temperature of dams on eyelid opening and body weight of pups in mice

Effects of the mandibular gland ectomy and environmental temperature to pups in Jcl: ICR mice were studied. In normal environmental animal room (A room; Tem. 23 +/- 2 degrees C, R. H. 50 +/- 10%), the mammary gland weights of lactating mothers and the body weights of pups in sialoadenectomized groups were slightly smaller than that of control groups during lactating period, whereas the eyelid opening of pups was not different between both groups and all pups exhibited complete eyelid opening on 14th day after birth. On the other hand, in cold environmental animal room (B room; Tem. 15 +/- 2 degrees C, R. H. 60 +/- 20%), the mammary gland weights of lactating mothers and the body weights of pups in sialoadenectomized groups were smaller than that of sialoadenectomized groups in A room and the eyelid opening of pups was considerably delayed when compared with that of control groups. The pups exhibited complete eyelid opening at 16th day after birth. These results were caused by mandibular gland ectomy and considered to be easily influenced by environmental conditions.     

Developmental plasticity in thyroid function primed by maternal hyperleptinemia in early lactation: a time-course study in rats

Pups whose mothers were leptin-treated during the last 3 days of lactation have thyroid dysfunction at adulthood. However, there was no report about leptin treatment in the first days of life or about its action on thyroid function during development. Here, we evaluated the effects of maternal leptin treatment on the first 10 days of lactation upon thyroid function of the offspring at 21, 30, and 180 days old. At birth, lactating Wistar rats were divided into: Leptin (Lep) - leptin-treated (8 μg/100 g of body weight, s.c.) for the first 10 days of lactation and Control (C, saline-treated). Mothers were killed at the end of lactation and their offspring at 21, 30, and 180 days old. Triiodothyronine (T3), thyroxine (T4), thyrotropin (TSH), and leptin levels in serum and milk were measured. Liver mitochondrial glycerolphosphate dehydrogenase (mGPD) activity was determined. Significant differences had p<0.05. At the end of lactation, Lep mothers had higher milk T3 (+ 30%), while their offspring had higher serum T3 (+ 20%) and TSH (+ 84%). At 30 days-old, Lep offspring showed lower TSH ( - 48%), T3 ( - 20%), and mGPDm ( - 42%). At 180 days-old, Lep group presented hyperleptinemia (1.4-fold increase), higher serum T3 (+ 22%), and lower mGPD activity ( - 57%). Maternal hyperleptinemia on lactation causes hypothyroidism in the pups at 30 days, which may program for higher serum T3 at adulthood. In conclusion, maternal hyperleptinemia during lactation, that is common in obese mothers, may have an impact in future disease development, such as thyroid dysfunction.     

Differential Growth of Own and Alien Pups in Mixed Litters of Mice: A Role for Genomic Imprinting?

Female mice are said to be unable to distinguish own from alien offspring and will indiscriminately nurse each other's young in communal nests. Here, we present results of a split‐litter experiment that tested whether offspring growth was affected depending on whether they were nursed by their own or unrelated foster mothers. Pups of reciprocal crosses between C57/B6 and CBA/Ca strains were fostered in mixed litters that consisted half of their natural siblings and half of unrelated littermates of the reciprocal genotype. Analysing the relative growth of the two pup types showed that offspring gained proportionally more weight when nursed by their own mothers than their cross‐fostered litter mates during the period from day 15 until weaning, during which maternal provisioning effort contributes to pup weight gain. Before day 15 of the pups’ life, however, we found no advantage of being nursed by biological mothers, and we suggest that this may be due to the effects of paternally expressed genes in young that mask their maternal identity, thus favouring indiscriminate nursing of all young in a communal nest.     

Maternal food restriction delays weaning in the guinea pig, Cavia porcellus

In mammals, the duration of lactation varies much more than other life history parameters in relation to body mass, both within and between species. The causes of this variation are poorly understood and seem to result from varying conditions of mothers and young. We studied the effect of long-term maternal food restriction on litter mass at birth, duration of lactation and offspring development in the precocial guinea pig. Mild experimental food restriction during reproduction resulted in prolonged nursing behaviour of mothers. Evidence for a threshold mass at weaning was, however, equivocal. In the guinea pig, benefits of prolonged lactation prove hard to understand, because nutritional benefits are minor. Independently of maternal food regime, pups terminated suckling attempts several days after mothers ceased nursing behaviour. The time between the last nursing behaviour and the last suckling attempts was not longer in litters with higher need, that is, in litters of food-restricted females, than in litters of females fed ad libitum. Under food restriction, mothers maintained their own body mass, leading in pups to lower mass at birth, reduced postnatal growth and lower body mass at maturity. Guinea pig mothers appear to be selected to value their own condition more than that of a litter. We suggest that lengthening of the nursing period under poor conditions is a life history response primarily of precocial mammals.     

Abnormalities in cloned mice are not transmitted to the progeny

Cloned animals suffer a wide range of severe fetal and placental malformations. Whether these malformations arise from insufficient epigenetic modifications or mutations has not yet been determined. To address this question, we examined siblings from both cloned XO and XY parents. These parents, which exhibited hypertrophic placentas, increased body weights, and open eyelids at birth, were created from the same ES cell sublines. The siblings from all three cloned pairs showed normal body and placenta weights and no open eyelids at birth. The results clearly showed that the phenotypic abnormalities seen in cloned mice were not transmitted to the progeny, a finding that suggests that abnormalities in cloned mice are responsible for insufficient epigenetic modifications/reprogramming.     

Lactating Females Do Not Discriminate Between Their Own Young and Unrelated Pups in the Communally Breeding Rodent, Octodon degus

Females in numerous rodent species engage in communal nesting and breeding, in which they share one or more nests to rear their young. A potential cost of communal nesting and breeding is that mothers divert resources to unrelated offspring. One way mothers could avoid this cost is to recognize and favour their own young over unrelated offspring when allocating maternal effort. We assessed whether female degus (Octodon degus), a communally nesting and breeding caviomorph rodent, discriminate between their own and unrelated offspring during lactation. Female degus previously have been shown to distinguish between their own and unrelated pups when exposed to odours from both. We measured pup discrimination based on differences in the retrieval behaviour of females that were in early or intermediate lactation directed towards their own and unrelated offspring; offspring presented were of similar or different age. Before any event of pup retrieval, lactating females spent similar amounts of time and interacted to a similar extent with their own and unrelated pups. During pup retrieval, all lactating females transported both pups to the nest. Neither relatedness to pups, nor pup‐age differences, influenced the order in which pups were retrieved to the nest. Dams waited similar amounts of time before retrieving the first pup when the first transported young was their own or unrelated. Likewise, females waited similar amounts of time before retrieving the second pup when the pup transported first was their own or unrelated. The time between first and second pup transport events was longer when dams were in early when compared with intermediate lactation, but only when pups were of similar age. All experimental subjects nursed unrelated pups after they were retrieved. Collectively, our results do not support the hypothesis that communally breeding female degus use their recognition ability to discriminate against unrelated offspring in favour of their own young.     

Involvement of the GHSR in the developmental programming and metabolic disturbances induced by maternal undernutrition

The mismatch between maternal undernutrition and adequate nutrition after birth increases the risk of developing metabolic diseases. We aimed to investigate whether the hyperghrelinemia during maternal undernourishment rewires the hypothalamic development of the offspring and contributes to the conversion to an obese phenotype when fed a high-fat diet (HFD). Pregnant C57BL/6 J, wild type (WT) and ghrelin receptor (GHSR)^−/− mice were assigned to either a normal nourished (NN) group, or an undernutrition (UN) (30% food restricted) group. All pups were fostered by NN Swiss mice. After weaning, pups were fed a normal diet, followed by a HFD from week 9. Plasma ghrelin levels peaked at postnatal day 15 (P15) in both C57BL/6 J UN and NN pups. Hypothalamic Ghsr mRNA expression was upregulated at P15 in UN pups compared to NN pups and inhibited agouti-related peptide (AgRP) projections. Adequate lactation increased body weight of UN WT but not of GHSR^−/− pups compared to NN littermates. After weaning with a HFD, body weight and food intake was higher in WT UN pups but lower in GHSR^−/− UN pups than in NN controls. The GHSR prevented a decrease in ambulatory activity and oxygen consumption in UN offspring during ad libitum feeding. Maternal undernutrition triggers developmental changes in the hypothalamus in utero which were further affected by adequate feeding after birth during the postnatal period by affecting GHSR signaling. The GHSR contributes to the hyperphagia and the increase in body weight when maternal undernutrition is followed by an obesity prone life environment.     

Development of echolocation and communication vocalizations in the big brown bat, <Emphasis Type="Italic">Eptesicus fuscus</Emphasis>

Big brown bats form large maternity colonies of up to 200 mothers and their pups. If pups are separated from their mothers, they can locate each other using vocalizations. The goal of this study was to systematically characterize the development of echolocation and communication calls from birth through adulthood to determine whether they develop from a common precursor at the same or different rates, or whether both types are present initially. Three females and their six pups were isolated from our captive breeding colony. We recorded vocal activity from postnatal day 1 to 35, both when the pups were isolated and when they were reunited with their mothers. At birth, pups exclusively emitted isolation calls, with a fundamental frequency range <20 kHz, and duration >30 ms. By the middle of week 1, different types of vocalizations began to emerge. Starting in week 2, pups in the presence of their mothers emitted sounds that resembled adult communication vocalizations, with a lower frequency range and longer durations than isolation calls or echolocation signals. During weeks 2 and 3, these vocalizations were extremely heterogeneous, suggesting that the pups went through a babbling stage before establishing a repertoire of stereotyped adult vocalizations around week 4. By week 4, vocalizations emitted when pups were alone were identical to adult echolocation signals. Echolocation and communication signals both appear to develop from the isolation call, diverging during week 2 and continuing to develop at different rates for several weeks until the adult vocal repertoire is established.     

Bioenergetics of reproduction and pup development in a subterranean rodent (Ctenomys talarum)

The objective of this study was to evaluate the maternal costs of reproduction and pup development in the subterranean rodent Ctenomys talarum (Thomas 1898). Statistical differences were detected in whole-animal metabolic rates between nonreproductive and pregnant or lactating females. Whole-animal metabolic rates during pregnancy and lactation were 128% and 151% of the resting metabolic rate (RMR) observed in nonreproductive females. The total additional energy cost of reproduction (above the nonreproductive level) was similar for both the gestation and lactation periods. Mass-specific RMR revealed an upregulation of cell or tissue metabolism during lactation but not during gestation. The mass-specific metabolic rate of pups was 237% of the adults' metabolic rates. No differences were observed in body temperature among nonreproductive, pregnant, or lactating females. No differences were detected in body mass at birth among pups from litters with different numbers of nestlings. Pups increased their body temperature, reaching adult temperature at 30 d of age, when they were near weaning. Milk constituted the exclusive food for pups until they started eating solid food at 10 d old. Suckling time decreased with age of pups, and at the same time, mother chases directed toward their pups increased. These reproductive characteristics may contribute to successful existence in a subterranean habitat.     

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%).     

Transfer of iodine through the milk in protein-restricted lactating rats

Iodine supply is important to avoid neonatal hypothyroidism. This study evaluated whether protein restriction during lactation affects iodine transfer to the pups through the milk. We studied lactating rats fed an 8% protein-restricted diet (PR), a control 23% protein diet (C), and an energy-restricted diet group (ER). On days 4, 12 and 21, mothers were separated from their pups for 4 h, injected with (131)I IP, and put together with their pups. The animals were killed 2 h later. PR pups had a significant decrease in iodine uptake in the gastric content and duodenal mucosa on the 4th day. On the contrary, at 12 and 21 days radioiodine was increased in the gastric content and in the duodenal mucosa. ER pups had an increase in iodine uptake in the gastric content and in the duodenal mucosa only at the end of lactation. The thyroid iodine uptake in PR pups was significantly decreased on the 4th day and significantly increased on the 21st day compared to control. When injected IP with an equivalent amount of (131)I, the PR pups had a decrease in thyroid iodine uptake on the 4th and 12th day, while ER pups had no significant changes. So, these data suggest that protein restriction during lactation was associated with lower iodine secretion into the milk in the beginning of lactation. However, at the end of lactation, an adaptation process seems to occur leading to a higher transfer of iodine through the milk that compensates the impairment of thyroid iodine uptake in these pups.