Puberty onset in the female offspring of rats submitted to protein or energy restricted diet during lactation

This study aims to determine the effects of maternal protein and energy malnutrition during lactation on the linear growth, body weight and onset of puberty of the female offspring. At parturition, dams were randomly assigned to the following groups: (C) control group, with free access to a standard laboratory diet containing 23% protein; (PR) protein-restricted group, with free access to an isoenergy and protein-restricted diet containing 8% protein; and (ER) energy-restricted group, receiving standard laboratory diet in restricted quantities. After weaning, the female pups had free access to standard laboratory diet. From day 30 onwards, the pups were inspected daily for vaginal opening. Cyclic stages of the ovaries were studied by daily vaginal smears after vaginal opening until day 40 when all animals were sacrificed with pentobarbital. From day 4 after birth until day 40, body weight and linear growth in the PR and ER rats were significantly lower than in controls (p < 0.001). In spite of the significant (p<0.05) delayed in the vaginal opening in PR and ER rats, the first estrous cycle occurred at the same time of vaginal opening in all groups. The PR and ER rats exhibited a lower uterine (PR = 42%, ER = 40%, p < 0.001) and ovarian (PR = 26%, ER=19%, p < 0.05) absolute weight and uterus relative weight (PR = 27%, ER = 22%, p < 0.05). Our data showed that maternal protein and energy malnutrition during lactation leads to growth retardation and delayed on the onset of puberty in female pups, with vaginal opening and estrous cycle occurring at the same time.     

Absence of anorectic effect to acute peripheral leptin treatment in adult rats whose mothers were malnourished during lactation.

Diets with restricted energy or protein during lactation programs body weight in the adult offspring. We have investigated the hypothesis that protein or energy-restricted diets during lactation alter the feeding response to peripheral leptin treatment of the adult offspring. Five Wistar rats were randomly assigned to one of the following groups on the day that the offspring were born: C, control diet with 23% protein; PR, protein restricted diet with 8% protein; and ER, energy-restricted, receiving the control diet in restricted quantities, which were calculated according to the mean ingestion of the PR group. After weaning (day 21), two animals from each litter (10 pups in each group) were randomly selected and placed together in the cage with free access to water and standard diet until 150 days of age, when they were tested for its response to either leptin (0.5 mg/kg body wt ip) for groups Clep, PRlep and ERlep or saline vehicle for groups Csal, PRsal and ERsal on food intake. In the control groups, food intake was reduced two hours (36%), four hours (41%) and six hours (25%) after leptin treatment. In contrast, no response was observed to leptin treatment in the PRlep and ERlep groups, suggesting leptin resistance. We demonstrated the development of resistance to the anorectic leptin effect and its program in a critical life period associated to nutritional and hormonal factors.     

Malnutrition during lactation changes growth hormone mRNA expression in offspring at weaning and in adulthood

Mothers' nutrition during lactation programs growth in their offspring. We studied the contribution of the growth hormone (GH) for this programming, evaluating GH mRNA expression. Lactating dams were grouped as follows: C, control diet with 23% protein; PR, 8% protein-restricted diet; and ER, energy-restricted diet, receiving the control diet in restricted quantities of the PR group's ingestion. Some pups were killed at weaning; the others received the control diet until they were sacrificed as adults. Pituitary GH mRNA was analyzed by Northern blot analysis. At weaning, the ER and PR animals had lower GH mRNA levels (-29% and -18%, respectively) and lower length as well as body weight. Ninety-day-old PR offspring showed a lower body length (-5%), whereas ER offspring showed a higher one (+5%); however, at 180 days, the lengths were not different. Both 90- and 180-day-old animals showed body weight differences against control animals, with PR offspring showing a lower (-10%) and ER offspring showing a higher (+12%) body weight. GH mRNA was higher in ER offspring at 90 and 180 days (+19% and +22%, respectively); it was lower in PR offspring at 90 and 180 days (-19% and -17%, respectively). Thus, we showed a direct relation between GH mRNA expression and length as well as body weight. We suggest that malnutrition during lactation may program GH mRNA expression patterns in adulthood and that these changes could be responsible for differences in growth patterns.     

Effects of maternal leptin treatment during lactation on the body weight and leptin resistance of adult offspring

We investigate whether leptin treatment to lactating rats affects food intake, body weight and leptin serum concentration and its anorectic effect on their adult offspring. Lactating rats were divided into 2 groups: Lep-single injected with recombinant rat leptin (8 microg/100 g of body weight, daily for the last 3 consecutive days of lactation) and control group (C) that received the same volume of saline. After weaning all pups had free access to the control diet, their body weight and food intake were monitored at each 4 days until 180 days of age, when they were tested for its food intake and response to either leptin (0.5 mg/kg body wt, ip) or saline vehicle. The offspring of the leptin-treated dams gained more weight and had higher food intake from day 37 onward (p<0.05), higher amount of retroperitoneal white adipose tissue (RPWAT) (37%, p<0.05) and higher leptin serum concentration (40%, p<0.05) at 180 days of age compared to control group. The food intake at 2, 4, 6 and 24 h was unaffected after acute injection of leptin in these animals, suggesting resistance to the anorectic effect of leptin. The maternal leptin treatment during lactation makes their adult offspring more susceptible to overweight with resistance to the anorectic effect of leptin.     

Maternal leptin treatment during lactation programs the thyroid function of adult rats

Recently, we showed that both maternal malnutrition during lactation and leptin treatment during the neonatal period program thyroid function. In this study we evaluate whether maternal leptin treatment during lactation programs thyroid function of the offspring in the adulthood. The dams were divided into 2 groups: Lep-daily sc single injected with 8 microg/100 g of body weight with recombinant rat leptin during the last 3 days of lactation and control group (C) that received the same volume of saline. The 180 day-old animals received a single i.p. injection of (125)I (2.22x10(4) Bq) and they were killed 2 h after the injection. Triiodothyronine (T3), thyroxine (T4), thyrotropin (TSH) and leptin concentrations were measured by radioimmunoassay. The milk of leptin-treated mothers on the last day of treatment had higher leptin (p<0.05) concentration. The pups of the leptin-treated mothers had at 21 days an unchanged T3, T4 and leptin serum concentrations with higher TSH (p<0.05). The offspring of Lep mothers had at 180 days a higher T3 (p<0.05) with normal thyroid (125)I uptake, T4 and TSH serum concentrations compared to the controls. So, the mother's hyperleptinaemia during lactation programs to a higher T3 serum concentration on the offspring, probably by a higher leptin transfer through the milk.     

Leptin treatment during the neonatal period is associated with higher food intake and adult body weight in rats.

For this study, we have determined the effects of neonatal leptin treatment on the evolution of body weight. Experiment 1: pups were divided into two groups: LepF - injected with leptin (8 micro g/100 g of body weight) for the first 10 days of lactation and control (C) - receiving saline. Experiment 2: pups were divided into two groups: LepL - injected with the same leptin concentration of experiment one for the last 10 days of lactation, and C, which received saline. Body weight and food intake were monitored until age 150 days, after which leptin concentrations were measured by ELISA. The LepF group had a significant increase in body weight (p < 0.05) from day 98 onward, in food intake (p < 0.05) from day 74 onward, and higher serum leptin concentration compared to the control (108 %, p < 0.05). The LepL group had a significant increase in body weight (p < 0.05) from day 113 onward, in food intake from day 121 onward (p < 0.001), and higher serum leptin concentration compared to controls (6.9 %, p < 0.05). These results suggest that both periods of lactation constituted a critical window for body weight and food intake programming, but the effects are more marked when the leptin is injected within the first ten days.     

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.     

Prolactin inhibition in lactating rats changes leptin transfer through the milk.

Malnutrition during lactation reduces milk production and changes pup's leptin serum levels. To test prolactin role in this nutritional state, we evaluated whether prolactin suppression during lactation changes serum leptin in dams, its transfer through the milk, and pup's serum leptin. Lactating rats were treated with bromocryptine (1 mg/twice a day, s.c.) or saline three days before sacrifice (days 2-4 or days 19-21). Food intake and body weight were measured until sacrifice (4th and 21st day). Serum prolactin and leptin were determined by radioimmunoassay. Bromocryptine injected dams had lower serum prolactin and milk production as expected. The mothers presented lower food ingestion (day 21: -25%), lower body weight (day 4: -12%; day 21: -10%), higher serum leptin (day 4: +68%), lower milk leptin on the 4th day (11 times) and higher (8 times) on the 21st day. The offspring of bromocryptine-treated mothers presented lower body weight in both periods of lactation and lower serum leptin on the 4th day (-40%) and higher on the 21st day (+37%) of lactation. We suggest that prolactin, through its effect on leptin secretion into the milk, may play an important role in signalizing maternal nutritional status to the pups.     

Long-term effects of malnutrition during lactation on the thyroid function of offspring.

Some studies have shown that the mother's nutritional condition may influence offspring's endocrine function through metabolic imprinting. Recently, we showed that the kind of maternal malnutrition during lactation affects adult body weight of the offspring and it is related to milk composition. We studied lactating rats fed an 8 % protein-restricted diet (PR), a control 23 % protein diet (C), and an energy-restricted diet group (ER). After weaning, all animals received a normal diet until they were 180 days of age. At this time, the animals received a single i. p. injection of (131)I and were sacrificed 2 h after the injection. Total triiodothyronine (TT3) and total thyroxin (TT4) serum concentrations were measured by enzyme immunoassay. The PR group had significantly a higher thyroid (131)I uptake, TT3 serum concentration and in TT4 serum concentration, compared to the controls. The ER group had only significantly higher TT3 serum concentration. These results showed that thyroid function regulation in adulthood may depend on maternal nutritional condition during lactation. Probably, PR group had a high thyroid function, whereas the ER group only had an increase in the deiodination of T4. The hyperthyroidism in the PR group could explain the low body weight observed in those animals.     

Leptin and prolactin, but not corticosterone, modulate body weight and thyroid function in protein-malnourished lactating rats.

To understand the role of hormonal changes in the lower food ingestion and body weight in protein-restricted lactating rats as well as the higher serum T (3), higher deiodination, iodide and T (3) milk transfer, we measured maternal serum prolactin, leptin, TSH and corticosterone, which are hormones that could influence those parameters. After birth, dams were separated into: control-fed with a 23 % protein diet (n = 12) and PR (protein-restricted)-fed with an 8 % protein diet (n = 12). At the 4 (th) and 21 (st) day of lactation, half of the animals in each group were sacrificed. PR dams presented hyperleptinemia (day 4: + 20 %; day 21: + 19 %; p < 0.05) and hypoprolactinemia (day 4: - 85 %; day 21: - 92 %; p < 0.05), which could help explain the lower food consumption and body weight in lactating PR rats since leptin is anorexigenic and prolactin is orexigenic. Also, this hyperleptinemia could contribute for the increase in serum T (3) of PR dams, since leptin stimulates T (3) production, especially acting on deiodinases. Serum corticosterone was not different between PR and C groups, and TSH was lower only at the end of lactation. Thus, we suggest that both leptin and prolactin could play an important role in the body weight and thyroid hormone changes observed in protein-malnourished lactating rats.     

Maternal tobacco smoke exposure during lactation inhibits catecholamine production by adrenal medullae in adult rat offspring

Previously, we have shown that maternal smoke exposure during lactation, even when pups are not exposed, affects biochemical profiles in the offspring at weaning, eliciting lower body adiposity, hyperinsulinemia, hypocorticosteronemia and lower adrenal catecholamine content. However, the future impact of tobacco exposure is still unknown. As postnatal nicotine exposure causes short- and long-term effects on pups' biochemistry and endocrine profiles, we have now evaluated some endocrine and metabolic parameters of the adult offspring whose mothers were tobacco exposed during lactation. For this, from day 3 to 21 of lactation, rat dams were divided in: 1) SE group, cigarette smoke-exposed (1.7 mg nicotine/cigarettes for 1 h, 4 times/day, daily), without their pups, and 2) C group, exposed to air, in the same conditions. Offspring were killed at 180-days-old. Body weight and food intake were evaluated. Blood, white adipose tissue, adrenal, and liver were collected. All significant data were p<0.05. The adult SE offspring showed no change in body weight, cumulative food intake, serum hormone profile, serum lipid profile, or triglycerides content in liver. However, in adrenal gland, adult SE offspring showed lower catecholamine content ( - 50%) and lower tyrosine hydroxylase protein expression ( - 56%). Despite the hormonal alterations during lactation, tobacco smoke exposure through breast milk only programmed the adrenal medullary function at adulthood and this dysfunction can have consequence on stress response. Thus, an environment free of smoke during lactation period is essential to improve health outcomes in adult offspring.     

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.     

Programmed obesity in intrauterine growth-restricted newborns: modulation by newborn nutrition

The degree of nutrient enhancement during the newborn period may modulate programming of appetite-regulating hormones, body composition, and propensity to adult obesity in intrauterine growth-restricted (IUGR) newborns. Pregnant rats received, from day 10 to term gestation and throughout lactation, ad libitum food (AdLib) or 50% food restriction (FR) to produce IUGR newborns. AdLib vs. FR offspring were studied at day 1, and, to create two distinct groups of newborn catch-up growth (immediate, delayed) among the IUGR newborns, cross-fostering techniques were employed. The four groups of pups at 3 wk were IUGR immediate catch-up growth (FR/AdLib), IUGR delayed catch-up growth (FR/FR), control (AdLib/AdLib), and lactation FR control (AdLib/FR). From 3 wk to 9 mo, all offspring had AdLib rat chow. Maternal FR during pregnancy resulted in IUGR pups (6.0 +/- 0.3 vs. 7.1 +/- 0.3 g, P < 0.01) with decreased leptin (0.66 +/- 0.03 vs. 1.63 +/- 0.12 ng/ml, P < 0.001) and increased ghrelin (0.43 +/- 0.03 vs. 0.26 +/- 0.02 ng/ml, P < 0.001). Maternal FR during lactation (FR/FR) further impaired IUGR offspring growth at 3 wk. However, by 9 mo, these pups attained normal body weight, percent body fat, and plasma leptin levels. Conversely, IUGR offspring nursed by AdLib dams (FR/AdLib) exhibited rapid catch-up growth at 3 wk and continued accelerated growth, resulting in increased weight, percent body fat, and plasma leptin levels. Thus the degree of newborn nutrient enhancement and timing of IUGR newborn catch-up growth may determine the programming of orexigenic hormones and offspring obesity.     

Neonatal low-protein diet changes deiodinase activities and pituitary TSH response to TRH in adult rats

Protein malnutrition during neonatal programs for a lower body weight and hyperthyroidism in the adult offspring were analyzed. Liver deiodinase is increased in such animals, contributing to the high serum triiodothyronine (T3) levels. The level of deiodinase activities in other tissues is unknown. We analyzed the effect of maternal protein restriction during lactation on thyroid, skeletal muscle, and pituitary deiodinase activities in the adult offspring. For pituitary evaluation, we studied the in vitro, thyrotropin-releasing hormone (TRH)-stimulated thyroid-stimulating hormone (TSH) secretion. Lactating Wistar rats and their pups were divided into a control (C) group, fed a normal diet (23% protein), and a protein-restricted (PR) group, fed a diet containing 8% protein. At weaning, pups in both groups were fed a normal diet until 180 days old. The pituitary gland was incubated before and after TRH stimulation, and released TSH was measured by radioimmunoassay. Deiodinase activities (D1 and D2) were determined by release of (125)I from [(125)I]reverse triiodothyronine (rT3). Maternal protein malnutrition during lactation programs the adult offspring for lower muscle D2 (-43%, P<0.05) and higher muscle D1 (+83%, P<0.05) activities without changes in thyroidal deiodinase activities, higher pituitary D2 activity (1.5 times, P<0.05), and lower TSH response to in vitro TRH (-56%, P<0.05). The evaluations showed that the lower in vivo TSH detected in adult PR hyperthyroid offspring, programmed by neonatal undernutrition, may be caused by an increment of pituitary deiodination. As described for liver, higher skeletal muscle D1 activity suggests a hyperthyroid status. Our data broaden the knowledge about the adaptive changes to malnutrition during lactation and reinforce the concept of neonatal programming of the thyroid function.     

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%).     

Cholecystokinin-8S levels in discrete hypothalamic nuclei of weanling rats exposed to maternal protein malnutrition

Perinatal malnutrition and growth retardation at birth are suggested to be important risk factors for the development of overweight and syndrome X in later life. Underlying mechanisms are unknown. Body weight and food intake are regulated, e.g. by hypothalamic neuropeptidergic systems which are thought to be highly vulnerable to persisting malorganization due to perinatal malnutrition. To investigate possible consequences for hypothalamic cholecystokinin-8S (CCK-8S) in the offspring, pregnant Wistar rats were fed an 8% protein diet during pregnancy and lactation (low-protein group; LP) while control mothers (CO) received a 17% protein isocaloric standard diet. LP offspring displayed underweight at birth (P < 0.05) and during suckling (P < 0.001), while leptin levels were not altered. At weaning, under basal conditions CCK-8S was decreased in LP offspring in the paraventricular hypothalamic nucleus and arcuate hypothalamic nucleus (P < 0.05), as well as in the dorsomedial hypothalamic nucleus, lateral hypothalamic area and ventromedial hypothalamic nucleus (P < 0.01). In summary, these data indicate (1) an inhibition of the satiety peptide CCK-8S in main regulators of body weight and food intake in low-protein malnourished newborn rats; (2) no direct relationship of hypothalamic CCK-8S to circulating leptin at this age; and (3) no neurochemical signs of hypothalamic CCKergic dysregulation in this animal model at the age of weaning.     

Maternal treatment with oleoyl-estrone induces resistance to lipid accrual in their descendants

Objective: To determine whether treatment of rat dams with oleoyl‐estrone (OE) has an effect on the offspring's long‐term response to diet restriction during lactation. Methods and Procedures: Control, OE‐treated, and diet‐restricted dams were treated up to day 15 of lactation. Changes in food intake and body weight were recorded for dams and their pups. After weaning, pups received a 4‐week standard diet followed by a 4‐week period of high‐fat diet. Lipid, protein, and energy content of pups plus energy intake and efficiency. Serum metabolites (glucose, urea, and cholesterol) and serum hormones (adiponectin, leptin, insulin, and sexual hormones). Results: Neither pups from dams in the OE‐treated nor in the diet‐restricted group showed significant changes in weight, though these two groups ingested 79% of food ingested by controls. At weaning, the pups from OE‐treated rats were smaller than those of the control or diet‐restricted groups. These pups maintained the differences in size and lipid content during the 4‐week standard‐diet period, whereas pups from diet‐restricted dams showed a sharp decrease in their lipid content. During the 4 weeks of high‐fat diet, the male offspring from OE‐treated dams increased the difference in lipid content in relation to the pups from control dams whereas in females the differences decreased. Female offspring from diet‐restricted dams showed the most marked changes in metabolite and hormone levels in relation to controls. Discussion: Treatment of lactating dams with OE programs the metabolic response of their offspring to resist the challenge of a high‐fat diet that would lead to obesity in adulthood.     

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.     

High-protein diet in lactation leads to a sudden infant death-like syndrome in mice

Background

It is well accepted that reduced foetal growth and development resulting from maternal malnutrition are associated with a number of chronic conditions in later life. On the other hand such generation-transcending effects of over-nutrition and of high-protein consumption in pregnancy and lactation, a proven fact in all developed societies, are widely unknown. Thus, we intended to describe the generation-transcending effects of a high-protein diet, covering most relevant topics of human life like embryonic mortality, infant death, and physical health in later life.

Methods

Female mice received control food (21% protein) or were fed a high protein diet (42% protein) during mating. After fertilisation, females stayed on their respective diet until weaning. At birth, pups were put to foster mothers who were fed with standard food or with HP diet. After weaning, control diet was fed to all mice. All offspring were monitored up to 360 days after birth. We determined glucose-tolerance and measured cardiovascular parameters using a tip-catheter. Finally, abdominal fat amount was measured.

Results and Conclusions

We identified a worried impact of high-protein diet during pregnancy on dams'' body weight gain, body weight of newborns, number of offspring, and also survival in later life. Even more important is the discovery that high-protein diet during lactation caused a more than eight-fold increase in offspring mortality. The observed higher newborn mortality during lactation is a hitherto non-described, unique link to the still incompletely understood human sudden infant death syndrome (SIDS). Thus, although offspring of lactating mothers on high-protein diet might have the advantage of lower abdominal fat within the second half of life, this benefit seems not to compensate the immense risk of an early sudden death during lactation. Our data may implicate that both pregnant women and lactating mothers should not follow classical high-protein diets.