Immunologic Profile of Immune Cells in Premature Neonates
Richard Hotchkiss, Anesthesiology
Washington University
This project will determine if the circulating level of IL-7 or the cell surface expression of IL-7 is decreased in premature neonates compared to full term neonates. Premature neonates have decreased numbers of lymphocytes compared to full term neonates and one reason for this difference could be that the levels of IL-7 or IL-7 receptor expression are not fully developed in the premature neonates as compared to full term neonates. IL-7 is essential for white blood cell formation.
Gestational Weight Gain in the Obese Gravida
George Macones, Obstetrics and Gynecology
Washington University
Purpose of this project is to study obese(BMI > 30) pregnant women in relation to adverse pregnancy outcomes, such as pre-term delivery, sever pre-eclampsia, intrauterine fetal demise, intrauterine growth restriction, gestational diabetes, hypertension and infection.
The primary aim will be a composite of major maternal and fetal morbidity in relation to the obese gravida (BMI >30). The components of the composite outcome are: severe preeclampsia, eclampsia, gestational diabetes requiring medication (A2), preterm delivery, intrauterine fetal demise, admission to the neonatal intensive care unit, intrauterine growth restriction, macrosomia, and shoulder dystocia. Secondary aim that we plan to examine include unplanned cesarean, mode of delivery, diet-controlled gestational diabetes (A1), mild preeclampsia, blood transfusions, infectious/febrile morbidity, length of hospital stay, chorioamnionitis, birthweight, and length of infant hospital stay.
The Functional Significance of Insulin in Testes and Sperm
Kelle Moley, Obstetrics and Gynecology
Washington University
Entry of glucose into the cell is facilitated by a family of glucose transporters known as the solute carrier family 2 (Slc2A). These transporters are characterized by the presence of 12 membrane-spanning helices and several conserved sequence motifs. There are currently 13 members of the solute carrier family: SlcA21-12 and Slc2A13, which was previously known as the H+ coupled myo-inosital-transporter (HMIT)[1,2].
Our laboratory has confirmed the presence of Slc2A8 in the Leydig cells and the innermost cells of the seminiferous tubules in the mouse testes as well as in the acrosome, midpiece and principal piece of mouse sperm. We have also localized Slc2A9a and Slc2A9b to the most intraseminiferous tubule cells and the Leydig cells of the mouse testes. GLUT9a localized to the midpiece of the sperm, and GLUT9b was found in the acrosome, midpiece, and principal piece of mouse sperm. This research also demonstrated the presence of insulin-containing granules in sperm.
Prior studies have confirmed the presence of insulin in human ejaculated sperm and it has been suggested that insulin may provide autocrine regulation of glucose metabolism by sperm. Research using mouse sperm confirmed these results and suggested that the expression of Slc2A9 and Slc2A8 may be regulated by insulin signaling and may play an important role in sperm maturation and fertilization. While the presence of insulin in human sperm has been identified, there has not yet been research confirming the expression of the Slc2A transporters in human sperm or further evaluating the insulin signaling and secretion pathways in human sperm.
Intrauterine Growth Retardation and Metabolomic Profiles
Marwan Shinawi, Pediatrics
Washington University, St. Louis Children’s Hospital
Our aim is to analyze the maternal serum metabolomic fingerprints and correlate these with the fetal metabolomes. We propose to compare the maternal and fetal metabolomes in intrauterine growth retardation (IUGR) and in uncomplicated pregnancies. Our ultimate aim is to find fetal and/or maternal “metabolomic signatures” that specifically characterize IUGR pregancies. Although this is not a direct aim of this study, our feto-maternal metabolomic data can be correlated in long-term studies with developmental delays, cognitive disabilities and behavioral abnormalities.
Metabolic Conditions and Pregnancy
Marwan Shinawi, Pediatrics
Washington University, St. Louis Children’s Hospital
The aim of this part of the study is to retrospectively analyze maternal body fluids (blood and urine) for specific metabolites that are relevant for a metabolic condition detected by abnormal newborn screen. This analysis would include serum aminoacids and acylcarnitine profile and urine organic acids. The data obtained will provide a proof of principle for the ability to detect these conditions prenatally and will increase our understanding of the complex feto-placental-maternal metabolic unit.
mtDNA on Fertility
Kelle Moley, Obstetrics & Gynecology
Washington University
Recent research has investigated the role of mtDNA on fertility. Wai et. al. found that embryos with the highest likelihood of successful development are those with the greatest mtDNA content; mitochondrial copy number in oocytes is directly related to fertility. Older women (>35 years of age), however, have decreased mtDNA copy number in oocytes and poorer ovarian response compared with younger women. Older women also have greater mtDNA mutations detected in blood samples, as evidenced by the common mutation 4977 bp in mtDNA. This group also found that an increased incidence of mtDNA mutations such as the mutation they specifically evaluated, as well as decreased mtDNA copy number in older woman, may reflect ovarian aging. Although these findings elucidated the role of mitochondria in fertility, little is known about the specific mutations and the level of heteroplasmy in mtDNA detected at the level of each oocyte. Previous research has investigated the role of oocyte mtDNA copy number or mtDNA mutations from blood samples; however, there is a lack of data investigating mtDNA mutations in a single oocyte. Our objective is to identify heteroplasmic mtDNA mutations at the level of a single oocyte that can lead to decreased IVF efficiency and fertility.
Occult Infections of Preterm Birth
Indira Mysorekar, Obstetrics & Gynecology
Washington University
Our overarching goal is to elucidate mechanisms underlying preterm birth (PTB), the leading cause of perinatal morbidity and mortality in developed countries. The syndrome of PTB can be initiated by inflammation, infection, premature activation of uterine activity or cervical ripening, and a variety of conditions characterized by placental dysfunction. Among these factors, intrauterine infection is prominently associated with PTB, yet the mechanisms by which intrauterine infections might trigger PTB are poorly understood.
We posit the novel concept that persistent and clinically occult infections, caused by organisms that form biofilms harboured within uterine tissues and inducing inflammatory cascades, represent one etiology of PTB.
Bacterial-Host Interactions in Blood and Amniotic Fluid
Amanda Lewis, Microbiology
Washington University
Bacterial infection is an important cause of perinatal complications. Our lab studies surface-expressed bacterial carbohydrate structures and their importance during bacterial infections of the bloodstream and amniotic fluid. We seek to better understand the mechanisms of bacterial immune evasion in these bodily fluids. To do this, we use bacterial genetic methods to create structural alterations in surface carbohydrate expression by various bacteria. Then we evaluate the ability of human blood, isolated blood cells or amniotic fluid to directly kill bacteria or tag them for elimination by immune cells. The WIHSC project provides blood and amniotic fluids for these investigations.
Bacterial-Host Interactions in Vaginal Fluids
Amanda Lewis, Microbiology
Washington University
Bacterial vaginosis (BV) is an imbalance of the vaginal flora characterized by diminished levels of lactic acid/hydrogen peroxide producing beneficial lactobacilli and an overgrowth of various anaerobic and fastidious bacteria. BV has been associated with at least a dozen different bacterial species, usually occurring as a polymicrobial infection. Reproductive-age women with BV are more likely to experience infections of the placenta and amniotic fluid; pre-term labor with delivery of premature low-birth weight infants; and increased susceptibility to other infections including HIV, pelvic inflammatory disease, postpartum endometritis and urinary tract infection. Unfortunately, this infection is often overlooked and can be extremely difficult to treat. Moreover, little is known about the basic mechanisms of BV or its complications. We are using vaginal specimens form pregnant women to better understand BV at a molecular level. One of the biochemical hallmarks of BV is the presence of sialidase activity in vaginal fluids. Sialidase is an enzyme that hydrolyzes carbohydrate residues called sialic acids from host cells and secreted glycoproteins. We are studying several host mucosal immune glycoproteins as substrates of BV sialidases and investigating the mechanisms by which sialidase activity promotes BV and complications that arise from BV in pregnancy. The WIHSC project provides vaginal swabs for these investigations.
A protein microarray for profiling maternal antibodies during pregnancy
Don Conrad, Biology and Biomedical Sciences
Washington University
This is a pilot, feasibility study to assess the potential for using ELISA-based technology to profile maternal sera for antibody biomarkers of maternal-fetal histoincompatibility, maternal pathogen exposure, and miscellaneous pregnancy complications. The primary end point of the study will be demonstration that our technology has sensitivity and specificity for detection of maternal antibodies against a known histocompatibility antigen, the Rhesus D blood group antigen.