Impact of maternal iron deficiency anaemia on the expression of the newly discovered multi-copper ferroxidase, Zyklopen, in term placentas.

In the present study, we investigated the effect of maternal iron deficiency anaemia (IDA) on expression of the newly discovered iron transporter, Zyklopen in term placenta, in 200 pregnant women. Placental expression of Zyklopen was studied by mRNA analysis and immunohistochemistry for the protein. In addition neonatal anthropometric parameters were also analysed. 58.8% of 200 subjects were anaemic. Both Zyklopen mRNA as well as protein expression in the placenta showed a statistically significant increase with increasing severity of anaemia. Although all the neonatal anthropometric parameters were lower in newborns of anaemic mothers, none showed any statistical significance. Zp mRNA levels did not show any significant correlation with newborn and placental parameters (except newborn skinfold thickness and head circumference). Similar to mRNA expression, Zp IHC expression correlated positively, albiet non-significantly, with newborn length and Hb levels, the correlation was however negative with birth weight, head circumference, mid-arm circumference unlike the mRNA expression, where it positively correlated with the above parameters. Our study for the first time demonstrated a definite increase in expression of Zyklopen at both mRNA and protein levels in term placenta, in maternal IDA.IMPACT STATEMENTWhat is already known on this subject? Iron deficiency anaemia (IDA) in a pregnant mother can lead to anaemia in the developing foetus; which is frequently observed to be of lesser severity than that in the mother. Recently a copper-containing oxidase called Zyklopen was discovered which was involved in iron efflux in BeWo cells. The gene encoding Zyklopen has been identified with a putative C-terminal membrane-spanning sequence and high sequence identitical to hephaestin (Heph) and ceruloplasmin (Cp), the other known vertebrate multicopper ferroxidase (MCF). Protein expression of this new MCF was observed in multiple diverse mouse tissues, including placenta and mammary gland.What do the results of this study add? Zyklopen protein immunohistochemical expression showed a statistically significant increase with increasing severity of anaemia. Similarly, placental mRNA expression of the Zyklopen gene was observed to be higher in anaemic mothers when compared to non-anaemic mothers. Our study for the first time demonstrated a definite increase in expression of Zyklopen at both protein and mRNA levels in term placenta, in maternal IDA.What are the implications of these findings for clinical practice and/or further research? This study will help us to understand better, the increased potential for influx of iron from mother to foetus in the condition of maternal iron deficiency. This study will help to determine how placental iron transport proteins can be regulated in response to maternal and neonatal iron status and will further our existing knowledge on relationships between maternal and neonatal iron status and mechanisms by which placental iron transport is modified in relation to these parameters.

Effect of Maternal Iron Deficiency Anaemia on the Expression of Iron Transport Proteins in the Third Trimester Placenta.

BackgroundDuring pregnancy, iron is transferred from mother to fetus with placental iron transport proteins (Transferrin receptor, Divalent metal transporter/DMT1, ferroportin/FPN1 and Zyklopen). The aim of the study was to evaluate the effect of maternal iron deficiency anemia on placental iron transporters. Study Design: Two hundred pregnant women, in third trimester of pregnancy were divided into anemic (Hemoglobin/Hb < 11g/dl) and non-anemic groups (Hb ≥ 11 g/dl). After delivery, placental expression of iron transport proteins were studied by immunohistochemistry and by mRNA analysis. Results: Of the 200 subjects, 59% were anemic. All 3 placental proteins showed statistically significant increase in immunohistochemical expression, proportionate to the severity of maternal anemia. The mRNA expression of DMT-1 gene was only significantly elevated in placentas of anemic mothers. Conclusion: Although in our study mRNA expression of only the DMT-1 gene was significantly high, immunohistochemically however all the 3 proteins showed significantly higher expression in placentas of anemic mothers.

Expression of iron transport protein Divalent metal transporter 1 (DMT1) increases in response to maternal iron deficiency anemia in near term to term placenta.

INTRODUCTION: Iron deficiency anemia (IDA) is the most prevalent nutritional deficiency disorder in pregnant women. During pregnancy, placental transport protein Divalent metal transporter1 (DMT1) plays a crucial role in transit of iron across placenta. The developing fetus is observed to be immune to anemia despite presence of anemia in the mother. Hence, we planned the present study to explore the effect of maternal IDA on the expression of DMT1 in the placenta. MATERIALS AND METHODS: Two hundred pregnant women recruited, were divided into anemic and nonanemic groups based on their predelivery hemoglobin levels (<11 g/dL and ≥11 g/dL respectively). After delivery, placental expression of DMT1 was studied by immunohistochemistry and mRNA analysis and neonatal anthropometry was performed. RESULTS: Of the 200 women recruited, 58.8% were anemic with 60.35% having moderate anemia. Most of the red cell parameters were observed to be higher in cord blood than mothers. DMT1 protein immunohistochemical expression showed a statistically significant increase with increasing severity of anemia. Similarly, placental mRNA expression levels of DMT1 gene were observed to be higher in anemic mothers in comparison with nonanemic mothers. CONCLUSION: Our study thus demonstrated a definite increase in expression of DMT1 at both protein and mRNA levels in term placenta, in maternal IDA.

Significance of Combined Analysis of High-Risk Human Papillomaviruses Polymerized Chain Reaction Analysis and Immunohistochemical Expression of p16INK4A in Cervical Cancer in a Cohort of South-Indian Population.

Introduction Cervical cancer is the fourth most frequent cancer in women worldwide, and it continues to be a big issue in developing countries. The current case-control study sought to determine the presence of high-risk human papillomaviruses (hr-HPV) in the development of cervical cancer, as well as their relationship with the cell cycle inhibitor gene p16INK4A in cervical cancer. Methods The association between p16INK4A protein and the presence of hr-HPV DNA in cervical lesions was explored in this study, which included 150 cervical cancer patients and 100 normal cervix samples. The immunohistochemistry approach was used to identify the expression of the p16INK4A protein, while the semi-quantitative polymerized chain reaction (PCR) method was used to identify the genomic identity of hr-HPV. Results About 90.67% (n=136) of the 150 case samples were found to be hr-HPV positive. Within the 136 HPV-positive samples, 45 (33.08%) show moderate expression of the p16INK4A protein, whereas 91 (66.91%) show overexpression, which is statistically significant (0.05). Among the 136 HPV-positive samples, 22.08% (N=30) were classified as having cervical intraepithelial neoplasia (CIN), with 56.66% (n=17) having CIN3, 36.66% (n=11) having CIN2, and 6.67% (n=2) having CIN1. Conclusion Based on the semi-quantitative immune staining scoring method of p16INK4A protein, genomic expression of HPV demonstrates that the expression of p16INK4A protein increases with the infectious load of the hr-HPV genome in the host cell. The result directly shows that immunostaining of the p16INK4A protein, in conjunction with the assessment of high-risk HPV in the host genome, will aid in the identification of cervical cancer in the cervix.