Prolonged in utero meconium exposure impairs spatial learning in the adult rat : Central Prize Award

Objective

The purpose of this study was to examine the effects of prolonged in utero meconium exposure on adult learning and memory, as measured by the Morris water maze.

Study design

Timed pregnant Long-Evans rats were studied. On gestational day 20 (term, 21 days of gestation), laparotomy was performed, and each maternal animal received an injection of clear amniotic fluid or meconium-stained amniotic fluid into each gestational sac. The laparotomy incision was closed, and the animals received postoperative monitoring through delivery. On postnatal days 145 to 148, the offspring underwent Morris water maze testing. The mean (±SEM) for the latency time was reported for each day's trial and compared between groups.

Results

There were significant differences between meconium-stained amniotic fluid group and clear amniotic fluid group in the mean time to platform on day 1 (82.7 ± 1.8 seconds vs 75.9 ± 3.0 seconds; P = .04), day 2 (60.5 ± 3.5 seconds vs 47. 8 ± 4.6 seconds; P = .03), and day 3 (56.5 ± 4.5 seconds vs 34.7 ± 4.4 seconds; P = .001). However, there were no differences on days 4 and 5. There were also no differences between recall and response learning trials that were done after a 12-day retention period.

Conclusion

In the absence of hypoxia or infection, prolonged in utero meconium exposure is associated with a delay of spatial learning in the adult rat.     

The effect of pre-eclampsia-like syndrome induced by L-NAME on learning and memory and hippocampal glucocorticoid receptor expression: A rat model

Objective: We aimed to study the impacts of pre-eclampsia on the cognitive and learning capabilities of adolescent rat offspring and to explore the possible underlying mechanisms at the molecular level. Methods: Pregnant rats were subcutaneously injected with saline solution (control) (n = 16) or NG-nitro-L-arginine methyl ester (L-NAME) (n = 16) from the 13th day of gestation until parturition. The brain tissues from fetal rats delivered by cesarean section were examined in both groups with hematoxylin and eosin (H&E) staining. Rats born vaginally in both groups were subjected to the Morris water maze test when 8-week-old and their hippocampi were analyzed for glucocorticoid receptor (GR) expression. Results: A pre-eclampsia-like model was successfully built in pregnant rats by infusion of the NO synthase inhibitor L-NAME, including phenotypes as maternal hypertension and proteinuria, high stillbirth rate, and fetal growth retardation. Neuroepithelial cell proliferation was found in the hippocampus of fetal rats in the L-NAME group. Grown to 8-week-old, the L-NAME group showed significantly longer escape latency than the control group in the beginning as well as in the end of navigation trials. At the same time, the swimming distance achieved by the L-NAME group was significantly longer than that of the control group. Such differences in cognitive and learning capabilities between the two groups were not gender dependent. Besides, the 8-week-old rats in the L-NAME group had increased GR expression in the hippocampus than the control group. Conclusion: Pre-eclampsia would impair cognitive and learning capabilities in adolescent offspring, and the upregulated expression of hippocampal GR may be involved in the underlying mechanisms.     

Preterm meconium-stained amniotic fluid is an ominous sign for the development of chorioamnionitis and for in utero cord compression

Purpose: Meconium-stained amniotic fluid (MSAF) is rarely observed in preterm pregnancies, and its clinical significance is undetermined. We evaluated the correlation between MSAF and obstetrical and perinatal complications prior to 34 weeks’ gestation.

Materials and methods: Pregnancies complicated with MSAF between 24 and 34 weeks of gestation were compared with same gestational age-matched controls. The variables measured were: obstetrical complications: clinical chorioamnionitis, Intrahepatic Cohlestasis of Pregnancy – ICP, Intra Uterine Growth Restriction – IUGR, preeclampsia, gestational diabetes; nonobstetrical complications; and perinatal complications: cord around neck/body, Apgar <7 at 5?min, cord pH, Neonatal Intensive Care Unit – NICU admission, complications during NICU hospitalization, and composite outcome.

Results: Higher incidence of clinical chorioamnionitis (15% versus 4.3%; p?=?0.041) and higher incidence of cord around the neck/body were found in the MSAF group in comparison with the clear AF group (27.4% versus 18.4%; p?=?0.04). No significant differences between the study’s groups were found in nonobstetrical complications or other perinatal complications investigated in our study.

Conclusion: MSAF in preterm pregnancy is an ominous sign for the occurrence of chorioamnionitis and for in utero cord compression. Therefore, MSAF in preterm pregnancies should be considered as a non-reassuring sign.     

水迷宫训练逆转孕期应激造成的子代海马NR2B表达的降低

目的:比较空间学习记忆中孕期应激子代和对照组子代海马空间学习功能密切相关蛋白NR2B的表达。方法:建立孕期束缚应激小鼠模型,在出生后第3周用酶联免疫法检测子代雄性小鼠血清皮质酮;在出生后第9周,采用免疫蛋白印迹和real-timePCR法检测子代雄性小鼠非空间学习记忆状态及空间学习记忆中海马NR2B的表达水平。结果:(1)基础状态下孕期应激子代血清皮质酮水平与对照组子代并无差异,应激状态下孕期应激子代血清皮质酮水平(43.7×104pg/ml)明显高于对照组子代(18.7×104pg/ml);(2)孕期应激雄性子代在出生后第9周海马NR2B mRNA和蛋白表达均显著低于对照组雄性子代。但经过空间学习记忆训练,两组海马NR2B蛋白水平无明显差异。结论:孕期应激减少子代海马神经元NR2B的表达,但水迷宫行为训练可逆转孕期应激造成的子代海马神经元NR2B的表达降低。     

Two fetal antigens (FA-1 and FA-2) and endometrial proteins (PP12 and PP14) isolated from amniotic fluid: localisation in the fetus and adult female genital tract

Monospecific antisera against two fetal antigens (FA-1 and FA-2), alphafetoprotein (AFP) and two endometrial proteins (PP12 and PP14) were used to examine the distribution of these proteins and antigens in human trophoblast and gestational endometrium in first and third trimesters of pregnancy, normal human ovary and fetal tissues by indirect immunoperoxidase histochemical localisation techniques.

Fetal liver stained exclusively for FA-1 and AFP which was used as a reference protein. Staining for FA-2 was seen in fetal connective tissue, in particular the basement membrane. FA-1 and FA-2 did not stain positively in decidua, trophoblast or ovarian tissue. Gestational endometrium stained positively for PP14 exclusively in the glandular epithelium, whilst staining for PP12 was seen only in the stromal cells. Trophoblast, both early and late, and ovarian tissue did not stain positively for any of the four substances tested.     

Prenatal exposure to phenobarbital and quantifiable alterations in the electroencephalogram of adult rat offspring.

OBJECTIVE: Our purpose was to measure central nervous system insult from prenatal phenobarbital by quantified electroencephalographic evaluation of mature rat offspring. STUDY DESIGN: Twenty-four adult female rats were given phenobarbital as 0, 20, 40, or 60 mg/kg/day subcutaneously between 9 and 10 AM for 28 days before breeding and throughout gestation. The electroencephalograms of 90-day-old offspring were sampled over 24 hours and converted to the power spectra. RESULTS: Female offspring exposed prenatally to 20 mg and males exposed prenatally to 40 mg displayed an increase in delta and a decrease in alpha and middle-beta waveform activities. Females exposed prenatally to 40 mg and males exposed prenatally to 60 mg displayed decreases in delta, theta, alpha, and middle-beta activities. CONCLUSIONS: Prenatal phenobarbital exposure produced dose- and sex-dependent changes in the electroencephalogram of mature offspring consistent with a generalized deficit in the neuronal synchronization mechanisms that are critical for normal sleep and learning.     

孕妇下生殖道解脲脲原体感染与妊娠结局关系的探讨

应用聚合酶链反应技术，对２１６例妊娠１２－３７周孕妇的宫颈阴道分泌物和其中１０９例有孕妇分娩时的羊水进行解脲脲原体ＤＮＡ检测，同时临床观察２１６例孕妇的妊娠结局。结果：宫颈阴道分泌物ＵＵ ＤＮＡ阳性率为４３．０６％，宫颈阴道ＵＵ ＤＮＡ阳性组对应的羊水ＵＵ检出率明显高于阴性组，两组平均孕周，平均出生体重，平均Ａｐｇａｒ评分以及胎儿窘迫，早产，剖宫产，低出生体重儿，低Ａｐｇａｒ评分和瘭生儿畸形的发五     

Effect of fetal dexamethasone exposure on the development of adult insulin sensitivity in a rat model

Objective. A rat model was designed to determine if fetal dexamethasone exposure is associated with decreased insulin sensitivity in adulthood, manifested as decreased binding of p85 to phosphorylated insulin receptor substrate-1 (IRS-1) within the phosphatidylinositol 3-kinase (PI 3-kinase) pathway of insulin signaling. Additionally, the study investigated whether a differential effect exists in male and female rodent offspring, such that females demonstrate decreased binding of p85 to IRS-1 after exposure to dexamethasone in utero.

Methods. Timed-pregnant Sprague-Dawley rats received either tap water or dexamethasone in drinking water from day 13 of gestation until delivery. Fasting male and female offspring from each group were sacrificed on day 50 of life, and half of these rats were given insulin subcutaneously prior to sacrifice. Adipocyte, skeletal muscle, and liver cell lysates were analyzed by immunoprecipitation and Western blotting of IRS-1 and IRS-1-associated p85.

Results. In all tissues examined, a significant inverse relationship was found between dexamethasone treatment in utero and association of p85 with IRS-1 in adulthood. p85 association with IRS-1 was similar in tissues from fasting and insulin-stimulated states. Furthermore, tissues of male and female rats demonstrated similar binding of p85 to IRS-1.

Conclusions. In a rat model, fetal exposure to dexamethasone was associated with decreased insulin signaling at the level of p85 binding to IRS-1, a proximal step in insulin signaling within the PI 3-kinase pathway. This effect did not appear to be enhanced by administration of insulin prior to sacrifice, nor was a sex-dependent differential effect noted.