Repeated antenatal corticosteroid treatments adversely affect neural transmission time and auditory thresholds in laboratory rats.

Antenatal corticosteroid (AC) treatment is given to pregnant women at risk for preterm birth to reduce infant morbidity and mortality by enhancing lung and brain maturation. However, there is no accepted regimen on how frequently AC treatments should be given and some studies found that repeated AC treatments can cause growth retardation and brain damage. Our goal was to assess the dose-dependent effects of repeated AC treatment and estimate the critical number of AC courses to cause harmful effects on the auditory brainstem response (ABR), a sensitive measure of brain development, neural transmission and hearing loss. We hypothesized that repeated AC treatment would have harmful effects on the offspring's ABRs and growth only if more than 3 AC treatment courses were given. To test this hypothesis, pregnant Wistar rats were given either a high regimen of AC (HAC), a moderate regimen (MAC), a low regimen (LAC), or saline (SAL). An untreated control (CON) group was also used. Simulating the clinical condition, the HAC dams received 0.2mg/kg Betamethasone (IM) twice daily for 6 days during gestation days (GD) 17-22. The MAC dams received 3 days of AC treatment followed by 3 days of saline treatment on GD 17-19 and GD 20-22, respectively. The LAC dams received 1 day of AC treatment followed by 5 days of saline treatment on GD 17 and GD 18-22, respectively. The SAL dams received 6 days of saline treatment from GD 17 to 22 (twice daily, isovolumetric to the HAC injections, IM). The offspring were ABR-tested on postnatal day 24. Results indicated that the ABR's P4 latencies (neural transmission time) were significantly prolonged (worse) in the HAC pups and that ABR's thresholds were significantly elevated (worse) in the HAC and MAC pups when compared to the CON pups. The HAC and MAC pups were also growth retarded and had higher postnatal mortality than the CON pups. The SAL and LAC pups showed little or no adverse effects. In conclusion, repeated AC treatment had harmful effects on the rat offspring's ABRs, postnatal growth and survival. The prolonged ABR latencies reflect slowed neural transmission times along the auditory nerve and brainstem auditory pathway. The elevated ABR thresholds reflect hearing deficits. We concluded that repeated AC treatment can have harmful neurological, sensory and developmental effects on the rat offspring. These effects should be considered when weighing the benefits and risks of repeated AC treatment and when monitoring and managing the prenatally exposed child for possible adverse effects.

Excess omega-3 fatty acid consumption by mothers during pregnancy and lactation caused shorter life span and abnormal ABRs in old adult offspring.

Consuming omega-3 fatty acids (omega-3 FA) during pregnancy and lactation is beneficial to fetal and infant development and might reduce the incidence and severity of preterm births by prolonging pregnancy. Consequently, supplementing maternal diets with large amounts of omega-3 FA is gaining acceptance. However, both over- and under-supplementation with omega-3 FA can harm offspring development. Adverse fetal and neonatal conditions in general can enhance age-related neural degeneration, shorten life span and cause other adult-onset disorders. We hypothesized that maternal over- and under-nutrition with omega-3 FA would shorten the offspring's life span and enhance neural degeneration in old adulthood. To test these hypotheses, female Wistar rats were randomly assigned to one of the three diet conditions starting from day 1 of pregnancy through the entire period of pregnancy and lactation. The three diets were Control omega-3 FA (omega-3/omega-6 ratio approximately 0.14), Excess omega-3 FA (omega-3/omega-6 ratio approximately 14.5) and Deficient omega-3 FA (omega-3/omega-6 ratio approximately 0% ratio). When possible, one male and female offspring from each litter were assessed for life span and sensory/neural degeneration (n=15 litters/group). The Excess offspring had shorter life spans compared to their Control and Deficient cohorts (mean+/-SEM=506+/-24, 601+/-14 and 585+/-21 days, p

Abnormal neurological responses in young adult offspring caused by excess omega-3 fatty acid (fish oil) consumption by the mother during pregnancy and lactation.

Consuming omega-3 fatty acids (omega-3 FA) during pregnancy and lactation benefits fetal and infant brain development and might reduce the severity of preterm births by prolonging pregnancy. However, diets that are relatively rich in omega-3 FA can adversely affect fetal and infant development and the auditory brainstem response (ABR), a measure of brain development and sensory function. We previously examined the offspring of female rats fed excessive, adequate or deficient amounts of omega-3 FA during pregnancy and lactation. The 24-day-old offspring in the Excess group, compared to the Control group, had postnatal growth retardation and poor hearing acuity and prolonged neural transmission times as evidenced by the ABR. The Deficient group was intermediate. The current study followed these offspring to see if these poor outcomes persisted into young adulthood. Based on prior findings, we hypothesized that the Excess and Deficient offspring would "catch-up" to the Control offspring by young adulthood. Female Wistar rats received one of the three diet conditions from day 1 of pregnancy through lactation. The three diets were the Control omega-3 FA condition (omega-3/omega-6 ratio approximately 0.14), the Excess omega-3 FA condition (omega-3/omega-6 ratio approximately 14.0) and Deficient omega-3 FA condition (omega-3/omega-6 ratio approximately 0% ratio). The Control diet contained 7% soybean oil; whereas the Deficient and Excess omega-3 FA diets contained 7% safflower oil and 7% fish oil, respectively. One male and female offspring per litter were ABR-tested as young adults using tone pip stimuli of 2, 4, 8 and 16 kHz. The postnatal growth retardation and prolonged neural transmission times in the Excess and Deficient pups had dissipated by young adulthood. In contrast, the Excess group had elevated ABR thresholds (hearing loss) at all tone pip frequencies in comparison to the Control and Deficient groups. The Deficient group had worse ABR thresholds than the Control group in response to the 8 kHz tone pips only. The Excess group also had ABR amplitude-intensity profiles suggestive of hyperacusis. These results are consistent with the Barker hypothesis concerning the fetal and neonatal origins of adult diseases. Thus, consuming diets that are excessively rich or deficient in omega-3 FA during pregnancy and lactation seems inadvisable because of risks for long-lasting adverse effects on brain development and sensory function.

Excess and deficient omega-3 fatty acid during pregnancy and lactation cause impaired neural transmission in rat pups.

Omega-3 fatty acids (omega-3 FA) consumption during pregnancy and lactation is beneficial to fetal and infant growth and may reduce the severity of preterm births. Thus, scientists and clinicians are recommending increasingly higher omega-3 FA doses for pregnant women and nursing babies for advancing the health of preterm, low birth weight, and normal babies. In contrast, some studies report that over-supplementation with omega-3 FA can have adverse effects on fetal and infant development by causing a form of nutritional toxicity. Our goal was to assess the effects of omega-3 FA excess and deficiency during pregnancy and lactation on the offspring's neural transmission as evidenced by their auditory brainstem responses (ABR). Female Wistar rats were given one of three diets from day 1 of pregnancy through lactation. The three diets were the Control omega-3 FA condition (omega-3/omega-6 ratio approximately 0.14), the Deficient omega-3 FA condition (omega-3/omega-6 ratio approximately 0%) and the Excess omega-3 FA condition (omega-3/omega-6 ratio approximately 14.0). The Control diet contained 7% soybean oil, whereas the Deficient diet contained 7% safflower oil and the Excess diet contained 7% fish oil. The offspring were ABR-tested on postnatal day 24. The rat pups in the Excess group had prolonged ABR latencies in comparison to the Control group, indicating slowed neural transmission times. The pups in the Excess group also showed postnatal growth restriction. The Deficient group showed adverse effects that were milder than those seen in the Excess group. Milk fatty acid profiles reflected the fatty acid profiles of the maternal diets. In conclusion, excess or deficient amounts of omega-3 FA during pregnancy and lactation adversely affected the offspring's neural transmission times and postnatal thriving. Consuming either large or inadequate amounts of omega-3 FA during pregnancy and lactation seems inadvisable because of the potential for adverse effects on infant development.

Leucinopine, a characteristic compound of some crown-gall tumors.

An unusual compound has been found in crowngall tumors induced by those Agrobacterium tumefaciens strains that utilize neither octopine nor nopaline. The compound has been isolated and shown by proton and carbon-13 NMR spectroscopy and by synthesis to be N(2)-(1,3-dicarboxypropyl)-L-leucine, which also exists in a cyclized (i.e., lactam) form. This compound, which we name "leucinopine," was not detected in octopine tumors, nopaline tumors, or the tumors induced by A. tumefaciens strains 181 and EU6.