Vitamin A deficiency during rat pregnancy alters placental TNF-alpha signalling and apoptosis

PROBLEM: Vitamin A is important for immune function and deficiency is associated with adverse pregnancy outcome. In the rat, vitamin A deficiency reduces both foetal number and neonatal survival. The role of the placenta is uncertain. The effects of maternal vitamin A deficiency on placental cytokines and apoptosis have been investigated. METHOD OF STUDY: Pregnant rats were fed either control or vitamin A free (VAF) diets (n = 4/group) from 8 weeks prior to and throughout pregnancy. Day 20 placentas from viable foetuses were examined for immunoexpression of (a) cytokines: tumour necrosis factor-alpha (TNF-alpha), TNFR1 receptor (p55), leptin and leptin receptor, (b) apoptosis: TdT-mediated dUTP nick end-labelling (TUNEL) positive cells, bax and bcl-2. RESULTS: Placentas from VAF rats, but not controls, exhibited an infiltrate of neutrophils positive for TNF-alpha and leptin. The number of TNFR1 (p55) and TUNEL positive trophoblast cells was increased specifically in areas of neutrophil infiltration. Trophoblast giant cells in VAF placentas exhibited reduced bax but no change in bcl-2. CONCLUSIONS: Maternal vitamin A deficiency is associated with abnormal placental apoptosis induced by neutrophil derived TNF-alpha acting through the TNFR1 (p55) and/or a change in the bcl-2/bax ratio in the trophoblast giant cells. These changes may underlie the effects of vitamin A deficiency on foetal development.     

Vitamin A levels and immunity in humans

In animal studies, vitamin A deficiency induces a shift from type 2 (humoral) to type 1 (cellular) cytokines; there are no similar data for humans. Control of human immunodeficiency virus (HIV) and Mycobacterium tuberculosis infections requires type 1 cytokine (cellular) immunity. These infections and vitamin A deficiency are highly prevalent in Africa. We therefore examined the interactions among serum vitamin A levels, immune parameters, HIV infection status, Mycobacterium bovis BCG vaccine scarring (as an indicator of a type 1 cytokine profile), and clinical findings for 70 hospitalized children in Malawi, Africa. Directly conjugated monoclonal antibodies and flow cytometry were used to assess cell-specific cytokine production by peripheral blood monocytes and lymphocyte subpopulations. The statistical techniques employed included nonparametric statistics and logistic regression analyses. Thirty percent of the participants had severe vitamin A deficiency (<10 microg/dl), 34% had moderate deficiency (10 to <20 microg/dl), and 36% had normal levels (> or = 20 microg/dl). Vitamin A levels were lower for HIV-positive than for HIV-negative children (median, 10 and 17 microg/dl, respectively). Vitamin A-deficient children (<20 microg/dl) were more likely than non-vitamin A-deficient children to have higher proportions of natural killer (NK) cells (median, 8.3 and 5.2%, respectively) and lower ratios of interleukin-10-producing monocytes to tumor necrosis factor alpha-producing monocytes after induction (median, 1.0 and 2.3, respectively). Vitamin A-deficient children were also more likely than non-vitamin A-deficient children to exhibit respiratory symptoms (47% versus 12%) and visible BCG vaccine scars (83% versus 48%), which are indicative of a type 1 response to vaccination. Vitamin A status did not vary with gender, age, incidence of malaria parasitemia, blood culture positivity, or rates of mortality (6% of vitamin A-deficient children died versus 20% of non-vitamin A-deficient children). Lower vitamin A levels were associated with a relative type 1 cytokine dominance and proportionately more NK cells, both of which may be somewhat beneficial to persons who are exposed to HIV, M. tuberculosis, or other type 1 pathogens.     

Vitamin D metabolism and function during pregnancy and the neonatal period

Recent evidence suggests that vitamin D plays an important role in calcium homeostasis during pregnancy and early extrauterine life. Vitamin D is metabolized by successive hydroxylations to 25-hydroxyvitamin D and then to 1,25-dihydroxyvitamin D, the most potent known metabolite of the vitamin. During pregnancy, the concentrations of this metabolite in maternal serum increase in parallel with the increased need to absorb dietary calcium. 1,25-Dihydroxyvitamin D is produced in the fetoplacental unit as well as in the maternal kidneys. Receptors for 1,25-dihydroxyvitamin D appear to be present in the placenta suggesting that the placenta may be a target for vitamin D action. Developmental changes in vitamin D metabolism and action have been documented in the neonate as well as in the mother and fetus. Clinical studies indicate that adequate vitamin D intake is important during pregnancy. Administration of vitamin D or its metabolites appears to be useful in the treatment of neonatal disorders.     

Changes in serum parathyroid hormone levels during pregnancy

As pregnancy poses a significant challenge to maternal calcium homeostasis, it is interesting to investigate a change in serum parathyroid hormone (PTH) level throughout pregnancy. PTH metabolism in pregnancy has not been clearly defined. We have made an attempt to evaluate changes in serum intact PTH level during pregnancy. Compared with nonpregnant women, serum intact PTH concentrations were decreased significantly in pregnant women during the first and the second trimester, but not during the third trimester. Nephrogenous cyclic AMP excretion, index of parathyroid function has been reported to be decreased in pregnant women during the first and second trimester, but to be in normal range in pregnant women during third trimester. Our finding consisted with these facts.     

Alterations in polyamine levels in amniotic fluid, plasma and urine during normal pregnancy

Polyamines have a close relationship with rapid cell proliferation. We measured polyamine levels in amniotic fluid, maternal plasma and urine during normal pregnancy. Plasma putrescine, spermidine and spermine gradually increased in the third trimester and reached the highest concentration at the end of pregnancy. There was a significant correlation between the level of these polyamines and the level of plasma estradiol and progesterone. In urine, putrescine and spermine increased with the progress of gestation and reached the highest level during the 8th to 10th months of gestation. In amniotic fluid, putrescine and spermidine concentrations were significantly high in the first trimester and decreased in the other trimesters, whereas spermine showed no significant change. Polyamine concentrations in maternal plasma and urine appear to reflect not only fetal metabolic changes but also the metabolic changes of the pregnant women, and to be influenced by several hormones which increase during pregnancy. Polyamines in amniotic fluid mainly reflect activated fetal metabolism and may be useful as biochemical indicators of fetal growth.     

Interleukin-8 levels and granulocyte counts in cervical mucus during pregnancy

PROBLEM: We measured interleukin-8 (IL-8) and granulocyte counts in cervical mucus to assess local immunity and parturition. METHOD OF STUDY: We detected IL-8 by enzyme linked immunosorbent assay (ELISA) and Western blotting. Granulocytes were counted on a slide glass containing mucus from the external cervical os. RESULTS: ELISA and Western blotting revealed IL-8 in cervical mucus from both nonpregnant and pregnant women. There were no significant differences in cervical mucus IL-8 levels or granulocyte counts between follicular, ovulatory, and luteal phases. However, IL-8 and granulocyte counts were significantly decreased after menopause. IL-8 and granulocyte counts were increased significantly during pregnancy, and were further increased after 38 weeks of gestation and at labor. IL-8 levels were significantly correlated with granulocyte counts, based on the study of 678 samples (P <0.0001). CONCLUSION: IL-8 is involved in the increase of cervical granulocytes and in the process of parturition.     

Changes of lipoxin levels during pregnancy and the monthly-cycle,condition the normal course of pregnancy or pathology

Inflammation Research - The purpose of the review was to gather information on the role and possibilities of using lipoxin in the treatment of infertility and maintaining a normal pregnancy....     

Serum leptin levels in different types of hypertension during pregnancy

We determined the serum levels of leptin in 96 pregnant women with body mass index between 20 to 30, 30 normal (NP), 26 with mild preeclampsia (MPE), 27 with severe preeclampsia (SPE), 6 with chronic hypertension plus preeclampsia (CHT+PE) and 7 with chronic hypertension (CHT). A significant (p < 0.01) decrease in leptin levels was observed in the SPE group when compared with the NP group. On the contrary, significant (p < 0.05) increases were observed in the CHT and CHT+PE groups when compared with the NP group. Leptin levels were significantly higher in the MPE (p < 0.001), CHT (p < 0.01) and CHT+PE (p < 0.5) groups when compared with the SPE. No significant differences were observed in the CHT group when compared with CHT+PE. Moreover, a positive correlation was encountered (r = 0.6, p < 0.001) between platelet number and leptin levels for all the patients with preeclampsia. These results suggest that leptin levels may be useful metabolic parameter in different types of hypertension during pregnancy.     

High altitude residence during pregnancy alters cytokine and catecholamine levels

This study assessed the impact of high altitude residence during pregnancy on parameters of maternal immune and endocrine system function. Urinary catecholamines, and serum cytokines, estriol, and cortisol were assessed during pregnancy in women living at moderate or high altitude. Women residing at high altitude exhibited elevated levels of proinflammatory cytokines only during pregnancy, and tended to have higher levels of catecholamines during pregnancy than women living at lower altitude. These data suggest that the combination of high altitude and pregnancy alters the maternal neural-immune axis in a manner that may predispose women to suboptimal birth outcomes.     

Mannose-binding lectin levels during pregnancy: a longitudinal study

BACKGROUND: Pregnancy is associated with changes in the immune system. Although previous studies have focussed mainly on adaptive immunity, there are indications that components of innate immunity, such as mannose-binding lectin (MBL), are associated with pregnancy outcome. Although this would suggest that pregnancy also involves adaptations in innate immunity, there are few studies in this area. Therefore, we aimed to determine whether MBL concentrations and the following steps in complement pathway activation are influenced by pregnancy. METHODS: MBL and Ficolin-2 concentrations, MBL-MBL-associated serine protease (MASP) complex activity, MBL pathway activity and classical complement pathway activity were determined by enzyme-linked immunosorbent assay (ELISA) in sera from pregnant women (n=32) during each trimester and post-partum. MBL genotyping was performed by PCR. RESULTS: During pregnancy, MBL concentrations increased to 140% [interquartile range (IQR) 116-181%, P < 0.0001]. This increase was already present at 12 weeks of pregnancy and was most pronounced in the high-production AA-genotype. Directly Post-partum MBL concentrations dropped to 57% of baseline (IQR 44-66%, P < 0.0001). Variations in MBL levels were reflected by similar changes in the following steps of complement activation, r > 0.93 (P < 0.01). Ficolin-2 levels and classical complement pathway activity were not similarly influenced by pregnancy. CONCLUSIONS: Pregnancy and the post-partum period profoundly influence MBL serum concentration and MBL complement pathway activity.     

Vitamin B12 levels and age

Vitamin B12 concentration was determined by radioassay in 179 healthy volunteers between the ages of 20 and 93 years in order to determine whether vitamin B12 levels decline with advancing age. The authors found no statistically significant decline in vitamin B12 levels in older individuals, nor a difference between males and females. A review of previous reports identifies potential reasons for controversy regarding the normal concentration of vitamin B12 in the elderly.     

Variations in anxiety levels during pregnancy and psychosocial factors in relation to obstetric complications

Patterns of variation of state and trait anxiety during pregnancy and after delivery were studied prospectively in relation to some obstetrical and neonatal disturbances. Specific pregnancy anxiety, social support, and coping style were also evaluated. State anxiety in the 3rd month was significantly higher among women with obstetric complications and oscillated during the course of pregnancy, with significantly higher levels in the 3rd and 9th months. No such variations were found in the women with uncomplicated pregnancies. None of the other psychosocial variables examined were related to complications.     

Dynamics of urinary levels of hCG during early pregnancy and accuracy of the home pregnancy test

Hum. Reprod., Advance Access published December 2, 2004,