Neonatal Offspring Research Articles

Hyperprolactinemia after neonatal prolactin (PRL) deficiency in rats: evidence for altered anterior pituitary regulation of PRL secretion.

Previous findings from this laboratory suggest a role for milk-borne PRL in the development of the inhibitory neuroendocrine controls over PRL secretion. Thus, rats that consumed milk deficient in PRL on days 2-5 postpartum show reduced concentrations and turnover of DA in the median eminence and elevated serum levels of PRL at 30-35 days of age. The present experiments were undertaken to investigate whether these consequences of neonatal PRL deficiency persist beyond puberty, and whether alterations in pituitary responsiveness to hypothalamic hormones may be involved. Lactating rats received sc injections of either saline or the dopamine (DA) agonist bromocriptine (125 micrograms/rat.day) on each of days 2-5 postpartum, a treatment that reduces the amount of PRL in milk without abolishing lactation. Blood samples were obtained from male and female offspring at various postnatal ages, and PRL concentrations were determined by RIA. Serum PRL concentrations in offspring from both groups were low until after weaning, but the female offspring of bromocriptine-treated mothers showed significantly elevated serum PRL between days 30 and 90 postpartum. Male offspring of bromocriptine-treated mothers also had transiently increased serum PRL levels, which returned to control levels by day 40. The turnover rate of DA in the median eminence, calculated from the rate of decline after synthesis inhibition, was reduced on day 35 in neonatally PRL-deficient offspring, as shown previously. However, no differences in DA turnover between the two groups were apparent on day 60, indicating a recovery of normal dopaminergic activity. Anterior pituitary cells of 100-day-old control and neonatally PRL-deficient animals were dispersed, cultured for 3 days, and then exposed to either TRH, to stimulate PRL release, or to the DA agonist bromocriptine, which inhibits PRL release. Pituitary cells of neonatally PRL-deficient offspring were almost completely unresponsive to bromocriptine with regard to suppression of PRL release and cytoplasmic PRL mRNA levels. In contrast, pituitary cells of neonatal PRL-deficient offspring were somewhat more responsive to TRH in stimulating PRL release and increasing the levels of PRL mRNA. These results suggest that a brief period of PRL deficiency during the neonatal period may result in long-lasting alterations in control of PRL secretion. The resultant hyperprolactinemia may be initiated by a reduction in the release of DA from the hyothalamus, perhaps reflecting a role for milk-derived PRL in the functional development of this neurosecretory system, and maintained in part by a reduction in pituitary responsiveness to DA.

Resistance ofSpodoptera frugiperda [Lep.: Noctuidae] to a nuclear polyhedrosis virus in the field and laboratory

Median lethal doses (LD50s) of nuclear polyhedrosis virus (NPV) were determined in neonatal offspring ofSpodoptera frugiperda (J. E. Smith) (Sf) larvae captured in southeastern Louisiana in 1981, 1982, and 1984. These LD50s ranged from 1.8 to 16.3 polyhedral inclusion bodies (PIB)/insect. The LD50s significantly (P<0.05) increased during the season of 1982 but had no pattern in 1981 or 1984. However, the Sf populations increased in heterogeneity of response to the NPV during all 3 years. The LD50 increased from 4.1 to 18.7 PIB/insect in a Sf laboratory colony exposed to the NPV LD80 for 7 generations, whereas in a control colony not exposed to NPV the LD50 was 5.9 PIB/insect after 7 generations.

Development of vaginal adenosis-like lesions and uterine epithelial stratification in mice exposed perinatally to diethylstilbestrol.

Pregnant ICR/JCL mice were given either four daily subcutaneous injections of 20-2000 micrograms diethylstilbestrol (DES)/day or a 4-day intravenous infusion of 20-200 micrograms DES/day starting on Day 15 of gestation. Female mice were injected with 0.01-50 micrograms DES/day for 5 days starting on the day of birth. Females given oil injections during the neonatal period and offspring of mothers given injections of an infusion of respective vehicles alone served as controls when corresponding ages were attained. Incidence of adenosis-like lesions (ADL) in the vaginal epithelium and stratification of the uterine epithelium (UST) were determined in both offspring and neonatally exposed mice at 30 days of age. Injections of 0.1-50 micrograms DES/day during the neonatal period induced ADL in the fornical epithelium of vagina (36-70%), but not UST. A high incidence of ADL (80-88%) was found in the fornical and upper-vaginal epithelia in offspring of mothers given injections of 200-2000 micrograms DES/day, and UST was encountered in 38-70% of these mice. Offspring of mothers given an infusion of 20 micrograms DES/day had low incidences of ADL (11%) and UST (22%), whereas offspring of mothers infused with 200 micrograms DES/day exhibited high incidences of ADL (71%) and UST (86%). In offspring of mothers given injections of 2000 micrograms DES/day, ADL appeared in the fornical and upper-vaginal epithelial as early as 15 days of age. Thus, the present study revealed that ADL and UST occur at a high incidence in infantile mice exposed prenatally to high doses of DES. Previous studies failed to detect such effects perhaps due to the strain of mice, methods, duration, and/or dose of DES used.

Transmission of maternal cytomegalovirus-specific immunity in the guinea pig

The prenatal and perinatal transmission of maternal cytomegalovirus (CMV)-specific immunity was studied in the guinea pig by cross-fostering newborns of seropositive and seronegative mothers. Resistance to CMV was assessed by challenging the newborn and adult offspring with sublethal doses of CMV and following the course of their acute CMV disease. Newborns were found to acquire detectable CMV antibody via the placental route but not the breast milk route. When compared to neonates with no acquisition of CMV immunity, neonatal offspring born to or foster fed on seropositive mothers were protected against generalized CMV infection to various degrees. The immunity transferred by pregnant mothers that had seroconverted prior to pregnancy was short lived and was more protective in newborns with detectable CMV antibody. Mothers that experienced primary CMV infection during pregnancy conferred on their progeny the most significant and long-lasting resistance against CMV challenge. This study demonstrates that newborn guinea pigs may acquire CMV-specific immunity from seropositive mothers; the degree of protection against CMV infection depends on the route of acquisition of immunity and on the time of maternal seroconversion.

The effect of maternal caffeine ingestion on pancreatic function in the neonatal rat.

Pancreatic function was investigated in neonatal suckling offspring of caffeine-ingesting dams, with or without maternal sucrose supplementation, throughout pregnancy and lactation. In offspring of rats ingesting caffeine without sucrose supplementation, there was initial hyperinsulinaemia, followed by a progressive fall of plasma insulin to subnormal levels. This fall in plasma insulin coincided with depletion of pancreatic insulin stores. Both the fall in plasma insulin and depletion of pancreatic insulin stores were prevented by sucrose supplementation of caffeine-ingesting dams. Offspring of dams fed sucrose alone and control offspring also maintained pancreatic insulin stores and circulating insulin levels over the first 14 days of postnatal life. Pancreases from offspring of caffeine-exposed animals tested in vitro showed enhanced sensitivity of the insulin release process to glucose. This was reflected in the glucose concentration required to elicit half-maximal insulin release (2.4 +/- 0.2 mmol/l for caffeine offspring, 2.3 +/- 0.2 mmol/l for caffeine with sucrose, 3.8 +/- 0.3 mmol/l for sucrose and 4.1 +/- 0.3 mmol/l for control offspring, mean +/- SEM). In contrast, offspring of sucrose-supplemented (with or without caffeine) dams showed increased sensitivity of the proinsulin biosynthetic process to glucose, whereas offspring of dams ingesting caffeine alone showed no significant enhancement of the biosynthetic process compared with control offspring. Thus enhanced sensitivity of the insulin secretory process to glucose without a change in the sensitivity of the biosynthetic process in the offspring of the caffeine ingesting (non-sucrose supplemented) dams could explain the progressive depletion of pancreatic insulin stores and eventual hypoinsulinaemia seen in this group.

Effects of in utero or suckling exposure to cerium (citrate) on the postnatal development of the mouse.

Gravid female mice received either a single subcutaneous dose of cerium citrate (80 mg Ce/kg) or an equivalent (in citrate) dose of sodium citrate on d 7 or 12 of gestation or on d 2 postpartum. To separate effects of prenatal and postnatal exposure, a cross-fostering design was employed. The weight and gross activity of the neonates were assessed on d 8 or 13 postpartum. Open-field behavioral parameters, accelerating rotarod performance, and passive avoidance learning were assessed on d 60-65 postpartum. Maternal offspring retrieval latency was measured on d 3 postpartum. Analyses revealed that neonatal weight was reduced both in offspring exposed to Ce in utero and in the offspring of mothers receiving Ce during lactation/suckling. Ce also appeared to affect maternal/offspring interaction: pups exposed prenatally to Ce were retrieved in less time than control pups. Except for an increased frequency of rearings in the open field of adult offspring exposed to Ce in utero, Ce exposure had no apparent effect on behavioral parameters, either in neonatal or adult offspring.

Effects of maternal ethanol consumption in rats on basal and rhythmic pituitary - adrenal function in neonatal offspring

Neonatal corticoid treatment delays development of the circadian rhythm of plasma corticosterone in rats. We therefore sought to determine whether fetal or neonatal exposure to ethanol, a substance which activates the hypothalamo - pituitary - adrenal axis, produces similar effects. Subjects were the offspring of dams fed a 5.0% w/v ethanol-containing liquid diet or pair-fed an isocaloric control diet during gestation weeks two and three or during postnatal week one. At birth (day 1), the fetal ethanol-exposed pups had significantly higher brain and plasma corticosterone levels than the pair-fed or normal controls; brain and body weights were unaffected. By day 3, brain and plasma corticosterone titers in the fetal ethanol-exposed pups declined to the levels of the pair-fed and normal controls, although brain weights were significantly reduced. Significantly higher p.m. than a.m. levels of plasma corticosterone first occurred on day 18 both in the fetal ethanol-exposed pups and in the pair-fed and normal controls. Thus, despite its causing elevated corticosterone levels at birth, fetal exposure to ethanol did not affect the onset of the pituitary - adrenal circadian rhythm. On the other hand, exposure to ethanol during the first neonatal week delayed the onset of the pituitary - adrenal rhythm from day 18 to day 21. However, even greater delays occurred in the neonatal pair-fed controls, suggesting that the delays following neonatal exposure were due to nutritional deficits rather than to alcohol per se. The developmental and long-term influences of elevated corticoid levels at birth in fetal ethanol-exposed rats on other aspects of pituitary - adrenal function remain to be determined.

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Serum reactivity to murine mammary tumor virus (MuMTV) was inversely related to mammary tumor risk in 8-to 22-week-old BALB/cfC3H breeding females. Mice at low tumor risk exhibited high-titered serum reactivity to MuMTV (50% end point, greater than or equal to 1:40 by radioimmunoassay) approximately 3-6 months earlier than did the mice at high tumor risk. Maternal MuMTV antibody levels were correlated with the serum anti-MuMTV reactivity of their neonatal offspring (2 wk of age). Serologic antiviral reactivity in infected mice did not change during periods of pregnancy and lactation. All infected animals had detectable serum MuMTV reactivity by 33 weeks of age. The virus-neutralizing capabilities of some of these sera were tested, Sera from some of the young, low-tumor-risk animals that had MuMTV-precipitating antibodies also had virus-neutralizing activity. Conversely, none of the sera from the high-tumor-risk animals had detectable MuMTV-neutralizing antibodies.

The Effects of Chronic Undernutrition Over Generations on Rat Development

Experimental rats were fed 2/3 (10g/24 hours) of adlibitum diet throughout pregnancy and post-weaning, thus far for six generations; their brain and body development was compared with those of controls fed ad libitum (15.5 g/24 hours). As expected from previous reports, neonatal F1 offspring exhibited highly significant decreases in body weight, cerebral wet weight, cerebral DNA and cerebral protein. However, neonatal decreases were not greater in F2 through F6 than in F1 indicating that there was no cumulative effect of this undernutrition on offspring's parameters over generations. Maternal body weight at mating (90 days) and percentage of females that did not litter steadily decreased over generations. The observed high mortality in F1 through F6 and the resulting strong natural selection in favor of best mothers and weanlings could explain these findings. The phenomena contributing to high mortality are multiple and involve maternal factors during pregnancy and before weaning, as well as offspring factors.

Contractile activity of neonatal heart cells in culture derived from offspring of exercised pregnant rats.

5-day-old neonatal offspring of exercised or non-exercised pregnant Sprague Dawley rats were used to prepare primary cultures of beating myocardial cells. The cells from the exercise group exhibited a slower beating rate for both single and aggregate cells; a larger cell size; an increased percentage of contracting cells; a greater capacity to form confluent monolayers, and a greater viability. It was concluded that exercise during the period of pregnancy produced morphological alterations in the myocardium of the progeny.