Gender differences at birth and differences in fetal growth

The discrepancy between the number of boys and girls born hasbeen interpreted as a natural selection response to differentialsurvival prospects. There also exists a discrepancy in birthweight, length, head circumference at birth of boys and girls;on the other hand, placental weights were not so strongly biasedby the sex of the fetus. Metabolic differences between the sexesare clearly recognized in adults. It is therefore argued thatthe anthropometric differences at birth, examples of which arepresented in this paper, can only be achieved if the productsof conception are also expressing a sexual bias in metabolismand physiology. It would then be this bias which would determinethe efficiency of the implantation and growth processes andlead to rates of survival to birth. The speculation arisingfrom this and the experimental manipulation of the sex ratiois that the physiological component most likely to be involvedwould be the lipid compartment with its strong sex difference.     

Transport of urea and amino acids through the isolated human placenta

By means of a method of two-way perfusion of the isolated human placenta the transport of urea from the fetal to the maternal placental circulation and the transport of amino acids in the opposite direction were studied. Experiments showed that the method provides for sufficiently complete perfusion of the intervillous space and creates suitable conditions for the study of placental transport. If the amino nitrogen concentrations in the two circulatory systems are equal, its concentration in the fetal circulation rises in the course of the experiment. On the addition of an amino acid to the maternal circulation, this increase develops to a greater degree. The results of these experiments confirm the view that amino acids are secreted by trophoblast cells into the fetal circulation.Laboratory of Biochemistry, Institute of Obstetrics and Gynecology, Academy of Medical Sciences of the USSR, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR M. A. Petrov-Maslakov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 4, pp. 394–397, April, 1976     

Transport of Proteins Across the Human Placenta

PROBLEM: The transport of various proteins across the human placenta was investigated by comparing maternal and fetal concentrations of tetanus antigen (TT-AG), anti-tetanus (TT)-immunoglobulin G (IgG) (following maternal vaccination), IgA, human chorionic gonadotropin (hCG), human placental lactogen (hPL), and alpha-fetoprotein (AFP) at term. METHOD OF STUDY: The concentrations of the six proteins were determined using enzyme-linked immunosorbent assay in serum of maternal venous and umbilical (fetal) vein samples obtained at delivery from uncomplicated term pregnancies (n = 16). RESULTS: The ratios (mean ± standard deviation) of fetal (umbilical) to maternal level were 1.41 ± 0.33 (anti-TT-IgG), 0.91 ± 0.37 (TT-AG), 0.002 ± 0.001 (IgA), 0.003 ± 0.001 (hCG), and 0.008 ± 0.004 (hPL), while the maternal:fetal concentration ratio of AFP was 0.002 ± 0.002. IgA, hCG, hPL, and AFP showed a close correlation between maternal and fetal levels varying between r² = 0.47 to 0.73 (P < 0.004–0.0001). Because AFP is produced by the fetus while IgA originates in the mother, the appearance of small amounts of these two proteins in the maternal or fetal compartment, respectively, suggests a slow rate of diffusion following a high concentration gradient. The detection of hCG and hPL in fetal serum is also interpreted as diffusion from the maternal into the fetal blood. Anti-TT-IgG has a significantly higher concentration in the fetal as compared with the maternal serum, which is in line with the well-documented active transfer of IgG. Fetal TT-antigen levels were similar to maternal concentrations, showing a close correlation (r² = 0.74, P < 0.0001) between the two proteins. CONCLUSIONS: The correlation between maternal and fetal concentrations of various proteins like IgA (150,000 Da), hCG (42,000 Da), and hPL (21,000 Da) suggests passive diffusion of these macromolecules across the placenta from the maternal to the fetal side, albeit at a slow rate. A similar process is postulated for AFP (70,000 Da) diffusing in the opposite direction from the fetus to the mother. There was no significant difference between the transplacental fetomaternal gradient of IgA and hCG and the maternal-fetal gradient of AFP. In view of the substantially larger volume of circulating maternal as compared with fetal blood, a significantly higher rate of crossing of AFP as compared with the other proteins must be assumed. It is uncertain whether a difference in the rate of transplacental transfer in the two directions or an additional source of AFP production in the maternal compartment explains the high maternal level. Anti-TT-IgG concentration is significantly higher in fetal than in maternal serum suggesting active transfer from the mother to the fetus. Furthermore, there is considerable transfer of TT-AG and a close correlation of fetal:maternal ratios of anti-TT-IgG (150,000 Da) and TT-AG (150,000 Da) could be an indication for a specific transfer of the antigen antibody complex.     

Pregnancy-Associated Uterine Granulated Metrial Gland Cells in Mutant and Transgenic Mice

PROBLEM: Granulated metrial gland (GMG) cells are pregnancy-specific uterine lymphocytes found in rodents. The lineage relationships of GMG cells are incompletely defined, although genetic and immunophenotyping studies suggest membership in the natural killer (NIC) cell lineage. Pregnancy-specific functions have been postulated for GMG cells, but no successful depletion of these cells has been achieved that would permit assessment of any critical roles that might influence gestational outcome. METHOD: Routine histological methods for light microscopy were used to assess implantation sites from wild-type mice and mice of the following genotypes: tgE26, mi/mi, and p53 knockout. RESULTS: GMG cells are transient, histamine-negative cells found in the pregnant uteri of most mice. Pregnancies in the NK and T-cell-deficient tgE26 were characterized by infrequent GMG cells, very small placentae, and an elevated rate of fetal and perinatal mortality. In term placentae of mi/mi with dystocia, GMG cells were found in a new location along the plane of placental separation, and they appeared degranulated. A normal life-history was observed for GMG cells in p53 knockout mice. CONCLUSION: Pregnancies in mutant and transgenic mice indicate that GMG cells are natural killer cells and have critical roles in placental development and pregnancy success. The disappearance of GMG cells at term is independent of p53 gene expression.     

Fas and Fas-ligand are expressed in the uteroplacental unit of first-trimester pregnancy

PROBLEM: Fas and Fas-ligand (FasL) are thought to provide a strategy for reducing graft rejection in immunologically 'privileged' tissues by controlling injurious lymphocyte reactions. As the uteroplacental unit is often defined as an immune-privileged site, we investigated the expression of Fas and FasL in this tissue in the first trimester of pregnancy. METHOD OF STUDY: Western blotting, immunohistochemistry, and double immunofluorescence were used for this examination. RESULTS: Western blotting with purified first-trimester trophoblast cells revealed one specific band for FasL. The presence of FasL on different trophoblast populations could be confirmed by immunohistochemistry and double immunofluorescence. In the villous part of the placenta, FasL is mostly located on cytotrophoblast cells with no access to maternal blood flow, whereas in trophoblast-invaded uterine tissue, interstitial trophoblast cells, which are in close contact with maternal leukocytes, revealed a strong signal for FasL, but no staining for Fas on these cells. However, Fas was found on CD45+ maternal leukocytes. CONCLUSION: Based on our experimental findings, we speculate that the abundant presence of FasL on trophoblast cells within the maternal decidua may play an important role in the maintenance of immune privilege in the pregnant uterus by endowing fetal trophoblast cells with a defense mechanism against activated maternal leukocytes, whereas in the villous part of the placenta, the Fas FasL system seems to be involved in the regulation of placental growth.     

Characteristics of histopathological and ultrastructural features of placental villi in pregnant Nepalese women

The placenta is an important functional unit for gas transfer between mother and fetus. The placental membrane, consisting of trophoblast layer interposed between maternal and fetal blood, plays an active role for intensity of respiration, but no morphological evidence has been documented. Until now, it has been reported that fetal growth retardation and increased fetal mortality rate usually could be seen at high altitude. In an attempt to find the cause of high perinatal mortality rate in Nepal, this study was undertaken to examine pathologically about 1000 Himalayan placentas obtained in Nepal and Tibet since 1977, and the results were compared with those of 5500 Japanese placentas at Saitama Medical School since 1990. In this study, characteristics of ultrastructural features of the Nepalese placental villi investigated in recent years are reported. (1) The gross characteristics of placental pathology in the Himalayan group were represented by marked subchorionic fibrin deposits and increased chorionic cysts in contrast to low incidence of intervillous thrombosis compared with those of the Japanese group. (2) As characteristics of histological findings of the placental villi between Himalayan and Japanese groups, the incidence of chorangiosis and chorangioma in the Himalayan group was significantly higher than that in the Japanese group. (3) Accompanying an increase of vasculosyncytial membrane (VSM) in the villi, thickness and separation of basement membrane of the syncytium in addition to increased apoptosis of syncytial cell nuclei were recognized. (4) As characteristic ultrastructural features of chorionic villi of Nepalese placentas, an increase of mitochondria and cystic formation of rough endoplasmic reticulum (rER), in addition to appearance of lamellar bodies similar to alveolar epithelial type II cell in organellae of the syncytium, were observed. These ultrastructural changes of the placental villous capillaries may be ascribed to hypevascularization caused by the chronic hypoxic state. It is, therefore, presumed that trophoblast cells may play an important role for gas transfer mecha-nism under such a hypoxic state at high altitude.     

Effect of beta2-glycoprotein I null mutation on reproductive outcome and antiphospholipid antibody-mediated pregnancy pathology in mice

beta(2)-Glycoprotein I (beta(2)GPI) is a principal target antigen for antiphospholipid antibodies associated with recurrent pregnancy loss and fetal growth restriction in women. The significance of disrupted beta(2)GPI activity in contributing to pregnancy pathology in antiphospholipid syndrome (APS) is not clear. In this study the physiological requirement for functional beta(2)GPI in pregnancy was investigated by evaluating reproductive outcomes in beta(2)GPI null mutant (beta(2)GPI-/-) mice. beta(2)GPI-/- mice were fertile and carried viable fetuses to term. However, there was an 18% reduction in the number of viable implantation sites in beta(2)GPI-/- mice and reduced fetal weight and fetal:placental weight ratio in late gestation, suggesting compromised placental function. Placental architecture was altered in beta(2)GPI-/- implantation sites with a 24% increase in the junctional zone: labyrinthine ratio, but placentae showed no evidence of increased thrombosis in the absence of beta(2)GPI. The effect of beta(2)GPI genotype on pregnancy success after passive transfer of human and mouse antibodies reactive with beta(2)GPI was also explored. Two of five anti-beta(2)GPI antibodies induced pregnancy loss in beta(2)GPI+/+ mice but beta(2)GPI-/- mice were refractory to antibody-induced pregnancy failure. We conclude that functional beta(2)GPI is not essential for successful pregnancy in mice, but optimal placental development and fetal growth require this molecule. Together these data are consistent with pathogenic mechanisms in antiphospholipid syndrome involving both neutralization of beta(2)GPI function and beta(2)GPI-immunoglobulin complex formation.     

Pre-term birth and severe pre-eclampsia are not associated with altered expression of HLA on human trophoblasts

PROBLEM: The unusual pattern of human leukocyte antigen (HLA) expression on human trophoblasts could play an important role in successful pregnancy outcome. To determine whether alterations in HLA expression are associated with pregnancy abnormalities we have investigated expression of these antigens on chorionic and extravillous cytotrophoblasts. METHODS: Frozen tissue sections of placenta and fetal membranes were collected after pre-term spontaneous delivery, severe pre-eclampsia pre-term Caesarean section, normal term delivery and term Caesarean section. HLA expression was analyzed by immunohistochemistry. RESULTS: We did not observe differences in the expression of HLA on chorionic and extravillous cytotrophoblasts in pregnancy abnormalities. However, we noted higher expression levels of HLA class Ia molecules in amnion epithelial cells in pre-term deliveries. Furthermore, in severe pre-eclampsia the number of extravillous cytotrophoblast islands were elevated when compared with pre-term deliveries. CONCLUSIONS: No alterations in expression of HLA class Ia, HLA-G and HLA class II on human trophoblasts in pregnancy abnormalities were seen.     

Quantitative and qualitative changes in the intraepithelial lymphocyte population in the uterus of nonpregnant and pregnant sheep.

PROBLEM: Previous studies have revealed the presence of a unique population of CD45R+ granulated cells in the sheep uterine epithelium. In the present study, dramatic changes in this cell population and in the nongranulated lymphocytes in the uterine and endometrial glandular epithelium of non-cycling, cycling, pregnant, and postparturient sheep are described. In noncycling and cycling sheep, the granules in the granulated intraepithelial cells were small. From days 55 to 134 of pregnancy, the granules in these cells were large, and there was a significant increase (P < 0.01) in the proportion of this cell population in the uterine epithelium but not in the endometrial glandular epithelium located in the deeper region of the stroma. The number of these cells declined dramatically (P < 0.01) from 2 to 15 days after parturition. Both the tissue distribution and the time of activation of these cells suggests they are different from the granulated lymphocytes described in placentae of mice and man. CONCLUSIONS: It is concluded that this unique population of granulated cells is derived from lymphocytes, and that these cells become metabolically active from mid- to late-pregnancy and may play a physiological role during pregnancy or birth. In contrast, the number of nongranulated intraepithelial lymphocytes were suppressed throughout pregnancy and they probably do not play a role in pregnancy.     

磁共振成像对前置胎盘的临床诊断价值

目的：探究磁共振成像（MRI）对前置胎盘的诊断价值。方法：选取2018年1月至2021年6月新疆生产建设兵团医院接诊的基于临床症状诊断为前置胎盘孕妇79例,所有孕妇均在手术前行盆腔MRI扫描,观察胎盘厚度、宫颈长度、胎盘T2低信号带、宫颈边缘窦、膀胱隆起、子宫肌层变薄信号,分析上述MRI征象、指标对前置胎盘的诊断价值。结果：79例孕妇中,最终经手术病理证实为前置胎盘的患者52例。MRI征象中的胎盘T2低信号带、宫颈边缘窦、膀胱隆起、子宫肌层变薄均可有效诊断前置胎盘（P <0.05）;检出率由高到低依次为：胎盘T2低信号带>宫颈边缘窦>子宫肌层变薄>膀胱隆起;胎盘厚度≥10 mm时,胎盘厚度与前置胎盘呈正相关（r=0.852,P=0.016）;胎盘厚度<10 mm时,胎盘厚度与前置胎盘无相关性（r=0.201,P=0.052）。宫颈长度≥30 mm时,宫颈长度与前置胎盘无相关性（r=0.376,P=0.071）;宫颈长度<30 mm时,宫颈长度与前置胎盘呈负相关（r=–0.721,P=0.036）。结论：MRI征象（胎盘T2低信号带、宫颈边缘窦、膀胱隆...