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Identification of kynurenine pathway enzyme mRNAs and metabolites in human placenta: up-regulation by inflammatory stimuli and with clinical infection.

OBJECTIVE: The purpose of this study was to determine whether placental-derived kynurenines (neuroactive metabolites that are derived from tryptophan) contributes to infection-mediated fetal cerebral injury. STUDY DESIGN: Placentae and cord blood were obtained from term deliveries (n = 16) and preterm deliveries with or without intrauterine bacterial infection (n = 8 per group). We investigated whether the placenta expressed messenger RNAs of kynurenine metabolite-forming enzymes, the effects of infection in vivo on the expression of these enzymes by the placenta, the in vitro effects of bacterial endotoxin lipopolysaccharide on expression and kynurenine metabolite output by the placenta, and the kynurenine metabolite levels in umbilical cord blood. RESULTS: Placentae expressed messenger RNA of tryptophan-degrading enzymes and synthesized several compounds. The expression of several enzymes increased significantly in placentae that were exposed to infection and/or lipopolysaccharide. Lipopolysaccharide also induced significant increases in placental kynurenine and quinolinic acid output. Kynurenine and quinolinic acid in cord blood of fetuses who were exposed to infection were elevated significantly. CONCLUSION: Inflammatory mediated release of kynurenines from placentae exposes the fetus to significant amounts of potentially neurotoxic substances.

Case-Control Studies↗

Transfer of ciprofloxacin, ofloxacin and levofloxacin across the perfused human placenta in vitro.

OBJECTIVE: To investigate the transfer of therapeutically important fluoroquinolones: ciprofloxacin, ofloxacin and levofloxacin, through the isolated perfused human placenta, from the maternal to the fetal compartment. STUDY DESIGN: Isolated placental cotyledons from normal human term placentae were dually perfused with M199 medium enriched with 3g/l bovine serum albumin and 1g/l glucose. Perfusion rates were 12 and 6 ml/min in the maternal and fetal circulation, respectively. Maternal and fetal closed circulation was used to evaluate steady-state concentrations and transplacental gradient formation. Eighteen placentae were used in our study: six for each experiment with ciprofloxacin, ofloxacin and levofloxacin were added to the maternal circulation. Samples were collected from the maternal and fetal compartments. Antipyrine was used as a reference drug that crosses the placenta by simple diffusion. The concentrations of ciprofloxacin, ofloxacin, levofloxacin and antipyrine were measured by specific HPLC (high performance liquid chromatography) methods. Results are presented as mean+/-S.D. RESULTS: In all the placentae, ciprofloxacin, ofloxacin, levofloxacin crossed the placenta from the maternal to the fetal compartment. The mean transplacental transfer percent of ciprofloxacin was 3.2+/-0.7% and the transplacental transfer index, the ratio of transplacental transfer between ciprofloxacin and antipyrine was 0.34+/-0.12. The mean transplacental transfer percent of ofloxacin was 3.7+/-2.4% and the transplacental transfer index was 0.33+/-0.3. The mean transplacental transfer percent of levofloxacin was 3.9+/-1.5% and the transplacental transfer index was 0.34+/-0.2. CONCLUSIONS: Only a small fraction of ciprofloxacin, ofloxacin and levofloxacin passed from the maternal to the fetal compartment. This fraction is significantly smaller compared to antipyrine. This may indicate that there is a barrier to the transport of fluoroquinolones in human placenta.

Anti-Infective Agents↗

Ultrasonic detection and developmental changes in calcification of the placenta during normal pregnancy in mice.

High resolution ultrasound imaging of the mouse placenta during development revealed highly echogenic foci localized near the materno-placental interface in early gestation and, near term, in the placental labyrinth (the exchange region of the placenta). Echogenic foci and calcium deposits identified in histological sections using Alizarin red staining showed similar localization and changes with gestation. Calcium deposits caused the echogenic foci because incubating uteri in a decalcifying solution eliminated both the deposits and echogenic foci. Transmission electron microscopy, X-ray microanalysis, and electron diffraction were used to show that deposits were calcium hydroxyapatite crystals. Calcium deposits were extensive and densely packed at days 7.5-9.5 of gestation at the border between the maternal decidua and the fetal trophoblast giant cells of ectoplacental cone. After the formation of the chorio-allantoic placenta (approximately day 10.5), calcification deposits appeared larger and more rarefied but were still localized at the border between the maternal decidua and the fetal trophoblast giant cells of the placenta. Calcification deposits were not observed in the labyrinthine region of the mouse placenta until > or = day 15.5 (day 18.5 is full term). We conclude that deposits of calcium hydroxyapatite crystals in the mouse placenta are detectable by high resolution ultrasound imaging. These deposits provide an ultrasound detectable marker of the maternal-placental interface that is particularly prominent during the establishment of the chorio-allantoic placenta between days 7.5 and 9.5 of gestation.

Animals↗

Progesterone synthesis by the human placenta.

One of the essential roles of the human placenta is to produce the steroid hormone progesterone, which is required for the maintenance of pregnancy. The rate-determining step of placental progesterone synthesis is the conversion of cholesterol to pregnenolone by cytochrome P450scc (CYP11A1) in placental mitochondria in a reaction requiring electrons delivered via adrenodoxin reductase and adrenodoxin. Pregnenolone is converted to progesterone by type 1 3beta-hydroxysteroid dehydrogenase located in the mitochondrion. Progesterone synthesis by the human placenta displays notable differences from steroid synthesis in the classical steroid producing tissues such as the adrenal cortex and corpus luteum. One important difference is that the placenta lacks short term modulation of steroid synthesis and does not express the steroidogenic acute regulatory (StAR) protein. The most notable difference between the placenta and other steroidogenic tissues is that electron supply to P450scc limits the rate at which cholesterol is converted to pregnenolone in the placenta. The limiting component for electron delivery to P450scc is the concentration of adrenodoxin reductase in the mitochondrial matrix which is insufficient to maintain the adrenodoxin pool in a fully reduced state. Evidence suggests that placental mitochondria have a near-saturating cholesterol concentration for P450scc, likely provided by the StAR-like protein MLN64, and cholesterol translocation to the P450scc is not a major site of regulation of progesterone synthesis. Cyclic AMP stimulates progesterone synthesis by the human placenta but uncertainty remains regarding the key hormones that control cyclic AMP levels. The mechanism of regulation of adrenodoxin reductase levels in the human placenta remains to be studied.

Abortion, Spontaneous↗

Lipopolysaccharide treatment downregulates the expression of the pregnane X receptor, cyp3a11 and mdr1a genes in mouse placenta.

The cytochrome P450 3A (CYP3A) is a member of the cytochrome P450 monooxygenase superfamily. The multidrug resistance 1 (MDR1) gene belongs to the ATP-binding cassette (ABC) family. Pregnane X receptor (PXR) is a nuclear receptor that regulates its target gene transcription in a ligand-dependent manner. Lipopolysaccharide (LPS)-induced downregulation of PXR, CYP3A and MDR1 in liver has been demonstrated in a series of studies. However, it is not clear whether LPS represses the expression of PXR, CYP3A and MDR1 in placenta. In the present study, we investigated the effects of LPS on the expression of PXR, cyp3a11 and mdr1a in mouse placenta. Pregnant ICR mice were injected intraperitoneally with different doses of LPS (0.1-0.5 mg/kg) on gestational day (gd) 17. Placental PXR, cyp3a11 and mdr1a mRNA levels were determined at 12 h after LPS treatment using RT-PCR. Results showed that LPS significantly downregulated PXR, cyp3a11 and mdr1a mRNA levels in a dose-dependent manner. LPS-induced downregulation of PXR, cyp3a11 and mdr1a mRNA in placenta was significantly attenuated after pregnant mice were pre- and post-treated with alpha-phenyl-N-t-butylnitrone (PBN), a free radical spin trapping agent. Additional experiments revealed that LPS increased lipid peroxidation and proinflammatory cytokine expressions in mouse placenta, all of which were also attenuated by PBN. Furthermore, LPS-induced downregulation of PXR, cyp3a11 and mdr1a mRNA in mouse placenta was prevented by N-acetylcysteine (NAC). NAC also inhibited LPS-initiated lipid peroxidation, GSH depletion and proinflammatory cytokine expressions in mouse placenta. These results indicated that LPS downregulates placental PXR, cyp3a11 and mdr1a mRNA expressions. Reactive oxygen species (ROS) may be involved in LPS-induced downregulation of PXR, cyp3a11 and mdr1a in mouse placenta.

ATP Binding Cassette Transporter, Subfamily B↗

Estrogen and progesterone receptor and hormone levels in human myometrium and placenta in term pregnancy.

Estradiol and progesterone receptors in the myometrium, decidua, placenta, chorion, and amnion of eight women who underwent elective cesarean section at term were determined by means of an exchange assay. The hormone levels in the peripheral plasma and cytosol of these tissues were measured by radioimmunoassays. Maternal plasma and the placenta had high concentrations of estradiol and progesterone, with the placenta having 12 times more progesterone than in maternal plasma but only half the concentrations of estradiol in maternal plasma. The decidua and placenta had detectable levels of cytosol and nuclear estradiol receptors, but the myometrium had no measurable cytosol estradiol receptors, whereas the chorion and amnion had neither cytosol nor nuclear estradiol receptors. However, the chorion and amnion had significantly higher concentrations of estradiol in the cytosol than those in the decidua and myometrium. Only the decidua and myometrium had cytosol and nuclear progesterone receptors, but the placenta, amnion, and chorion had neither cytosol nor nuclear progesterone receptors. In contrast, progesterone hormone levels were significantly higher in the placenta, amnion, and chorion than in the decidua and myometrium. The findings indicate that, in the term pregnant uterus, (1) the placenta, amnion, and chorion are rich in progesterone, estradiol, and nuclear estradiol receptors but have no progesterone receptors, (2) the decidua and myometrium have nuclear estradiol and progesterone receptors, and (3) the myometrium has a higher progesterone/estradiol ratio than that of the peripheral plasma, thus suggesting a highly progesterone-dominated uterus.

Amnion↗

The association between maternal cocaine use and placenta previa.

OBJECTIVE: Our aim was to determine whether maternal cocaine exposure is a risk factor for placenta previa. STUDY DESIGN: In this case-control study, cases of placenta previa confirmed at delivery (ascertained by International Classification of Diseases, ninth revision, Clinical Modification, code-based search, N = 40) were compared with a random sample of patients without placenta previa (N = 80) in a ratio of two controls per case. Data on antecedent maternal cocaine use, as well as other potential risk factors for placenta previa, were obtained from a review of the prenatal chart and the hospital record. Categorization of cocaine use was based on either patient self-report or urine toxicologic testing, or both. Multiple logistic regression was performed to assess the association between cocaine and placenta previa while we controlled for other variables. RESULTS: After the effects of other variables were adjusted for, maternal cocaine use was an independent risk factor for placenta previa (adjusted odds ratio = 4.39, 95% confidence interval 1.17 to 16.4). Other significant risk factors included a history of cesarean section and prior elective abortion. CONCLUSION: These results suggest that cocaine use, as well as prior cesarean section, prior elective abortion, and parity, are associated with placenta previa.

Adult↗

Regulation of interleukin 8 production in the term human placenta during labor and by antigestagens.

OBJECTIVE: Our purpose was to assess the effects of labor and antigestagens on production of interleukin 8 by the term human placenta and to localize interleukin 8 in first- and third- trimester placentas. STUDY DESIGN: The study was conducted by the Department of Obstetrics and Gynaecology of the University of Edinburgh. Five placentas were collected after spontaneous and cesarean deliveries. Explants were cultured in the presence of mifepristone, lilopristone, or onapristone. The production of interleukin 8 was determined by specific radioimmunoassay, and the immunolocalization of interleukin 8 was determined in sections of first- and third-trimester placentas. RESULTS: All explants produced interleukin 8. Production was significantly increased (P < .05) after spontaneous delivery. In placentas delivered spontaneously, onapristone significantly increased production of interleukin 8 (P < .05), whereas in those from cesarean deliveries lilopristone caused a significant increase in production (P < .05). In the third-trimester placenta interleukin 8 was localized in the perivascular area of fetal vessels. In first-trimester villi it was peripherally located in syncytiotrophoblast. CONCLUSION: The human placenta at term is capable of producing interleukin 8, which is localized around the perivascular area of the villi. Production is increased after spontaneous labor and to varying degrees by the antigestagens studied. Interleukin 8 may have a role in the onset of parturition by recruiting and activating neutrophils at the placental site.

Culture Techniques↗

Risk factors for abruptio placentae and eclampsia: analysis of 445 consecutively managed women with severe preeclampsia and eclampsia.

OBJECTIVE: Our purpose was to characterize the clinical presentation or laboratory variables predictive of either abruptio placentae or eclampsia in women with severe preeclampsia. STUDY DESIGN: Prospective collection of perinatal data from 445 consecutively managed women with severe preeclampsia and eclampsia. Univariate analysis was used to determine which of the independent variables were significantly different between the groups (abruptio placentae vs no abruptio placentae; eclampsia vs no eclampsia). Those with significant differences were then entered into multiple logistic regression analysis to determine those characteristics that were independently related to the outcome variable (abruptio placentae or eclampsia). Before multivariate analysis, the independent variables with an interval scale of measurement were converted to a dichotomous scale, with the receiver-operator characteristic curve used to determine a cutoff level. RESULTS: Univariate analysis revealed statistical significance for the following variables associated with eclampsia: uric acid concentration, > 8.1 mg/dL; proteinuria (>3+); headache; visual symptoms; deep tendon reflexes >3+; serum albumin concentration, <3 mg/dL; and serum creatinine concentration, >1.3 mg/dL. However, with subsequent multivariate analysis, only headache and deep tendon reflexes >3+ remained significant. Univariate analysis for variables associated with abruptio placentae revealed an association between bleeding and platelet count <60,000/mm3. There was no association between abruptio placentae and eclampsia and systolic, diastolic, or mean arterial pressure, quantitative proteinuria, epigastric pain, bleeding, gestational age at delivery, history of preeclampsia, or chronic hypertension. CONCLUSION: Quantitative proteinuria and degree of blood pressure elevation were not predictive of either abruptio placentae or eclampsia, as has previously been suggested. The greatest morbidity associated with eclampsia occurred in women with preterm gestations not receiving medical attention.

Abruptio Placentae↗

Plasmodium falciparum-infected erythrocytes adhere both in the intervillous space and on the villous surface of human placenta by binding to the low-sulfated chondroitin sulfate proteoglycan receptor.

In pregnant women infected with Plasmodium falciparum, the parasite-infected red blood cells (IRBCs) sequester in the placenta through chondroitin 4-sulfate (C4S)-mediated adherence. The pattern of IRBC adherence in P. falciparum-infected placenta has been controversial. Moreover, the identity of the chondroitin sulfate proteoglycan (CSPG) receptor, that mediates IRBC adherence, and its location in the placenta have not been established. This study, using immunohistochemical techniques, clearly shows, for the first time, that the low-sulfated CSPGs of the placenta are localized predominantly in the intervillous space. Ex vivo IRBC adherence analyses demonstrate that the IRBCs are adhered to the CSPG receptors in the placenta in a C4S-dependent manner. This IRBC binding pattern was similar to that observed in P. falciparum-infected placentas. These data and the results of dual-fluorescence staining of the endogenous RBCs and syncytiotrophoblasts, and co-localization of CSPG and IRBC adherence unequivocally establish that the low-sulfated CSPGs are the major natural receptors for IRBC adherence in the placenta. Further, it was found that IRBCs adhere mainly in the intervillous space and also at significant levels to the syncytiotrophoblasts. Finally, the ex vivo IRBC adherence method described herein provides a reliable procedure for future studies for the assessment of the efficacy of C4S inhibitors and adhesion inhibitory antibodies.

Animals↗

Obstetric implications of low-lying placentas diagnosed in the second trimester.

OBJECTIVES: To determine the obstetrical outcome of pregnancies initially complicated by a low-lying placenta in the second trimester. METHODS: We reviewed the obstetric outcome of all women with singleton deliveries from 1 January 1997 to 31 March 1999 and compared the 703 women with low-lying placentas (placentas in the lower uterine segment) with the 6938 women with placentas that were normally situated in the upper uterine segment at 16-22 weeks' gestation. RESULTS: Pregnancies complicated by a low-lying placenta in the second trimester were not associated with antepartum hemorrhage, preterm births, preterm prelabor rupture of membranes, pregnancy-induced hypertension, fetal growth restriction or cesarean births. However, they had a higher incidence of postpartum hemorrhage (odds ratio 1.768, 95% confidence interval 1.137, 2.748) than women with a normally situated placenta in the second trimester. CONCLUSIONS: Pregnant women with low-lying placentas in the second trimester have a higher incidence of postpartum hemorrhage and hence, it would be prudent to carefully manage the third stage of labor in these women.

Adult↗

Decreased maternal serum placenta growth factor in early second trimester and preeclampsia.

OBJECTIVE: To compare early second-trimester maternal serum placenta growth factor concentrations in patients with subsequent development of preeclampsia and those with normal pregnancies. METHODS: We conducted a case-control analysis of stored maternal serum of 27 women who subsequently developed preeclampsia and 227 randomly selected normal controls during the gestational period of 14-19 weeks. Using such a sample size, there was a greater than 95% power to test a difference in the primary study interest. A quantitative sandwich enzyme immunoassay was used to measure the maternal serum placenta growth factor concentration. For statistical analysis, Mann-Whitney U tests, multiple linear regression analysis, multivariable logistic regression model, and receiver-operating characteristic (ROC) curve were used. P <.05 was considered statistically significant. RESULTS: Maternal serum placenta growth factor concentration was associated with the occurrence of subsequent preeclampsia (P <.001) and gestational age (P <.001). The median (interquartile range) of multiples (MoM) of the gestational age stratified median for placenta growth factor in preeclampsia was 0.55 (0.33, 0.85). The ROC curve revealed that the specificity was 70% when the diagnostic sensitivity was 70%, and the optimal cutoff value of placenta growth factor MoM was 0.76. The risk of developing preeclampsia subsequently was increased 2.5-fold for maternal serum placenta growth factor concentration decrements of 0.1 MoM. CONCLUSION: A decreased maternal serum placenta growth factor concentration in the early second trimester is highly associated with the subsequent development of preeclampsia, but a large prospective study is needed to explore its use as an early predictor for the condition.

Adolescent↗

Risk factors for placenta accreta.

OBJECTIVE: To identify risk factors associated with placenta accreta in a large cohort study. METHODS: Data for this study came from the Taiwan Down Syndrome Screening Group, an ongoing project on feasibility of serum screening in an Asian population. Women who had serum screening for Down syndrome at 14-22 weeks' gestation using alpha-fetoprotein (AFP) and free beta-hCG between January 1994 and June 1997, and delivered in the same institution, were included (n = 10,672). Those who had multiple gestations (n = 200), overt diabetes (n = 11), or fetal malformations (n = 101) were excluded. If a woman was involved more than once, one randomly selected pregnancy was included in the analysis (n = 9349). Twenty-eight pregnancies were complicated by placenta accreta, diagnosed by clinical presentation (n = 26) or histologic confirmation (n = 2). Multiple logistic regression with adjustment for potentially confounding variables was used to identify independent risk factors for placenta accreta. RESULTS: Women who had placenta previa (odds ratio [OR] 54.2; 95% confidence interval [CI] 17.8, 165.5) and second-trimester serum levels of AFP and free beta-hCG greater than 2.5 multiples of the median (OR 8.3; 95% CI 1.8, 39.3 and OR 3.9; 95% CI 1.5, 9.9, respectively), and were 35 years and older (OR 3.2; 95% CI 1.1, 9.4) were at increased risk of having placenta accreta. CONCLUSION: Risk factors for placenta accreta include placenta previa, abnormally elevated second-trimester AFP and free beta-hCG levels, and advanced maternal age.

Adult↗

Neonatal outcomes with placenta previa.

OBJECTIVE: To identify neonatal complications associated with placenta previa. METHODS: This was a population-based, retrospective cohort study involving all singleton deliveries in Nova Scotia from 1988 to 1995. The study group consisted of all completed singleton pregnancies complicated by placenta previa; all other singleton pregnancies were considered controls. Patient information was collected from the Nova Scotia Atlee perinatal database. Neonatal complications were evaluated while controlling for potential confounders. The data were analyzed using chi2, Fisher exact test, and multiple logistic regression. RESULTS: Among 92,983 pregnancies delivered during the study period, 305 cases of placenta previa were identified (0.33%). After controlling for potential confounders, neonatal complications significantly associated with placenta previa included major congenital anomalies (odds ratio [OR] 2.48), respiratory distress syndrome (OR 4.94), and anemia (OR 2.65). The perinatal mortality rate associated with placenta previa was 2.30% (compared with 0.78% in controls) and was explained by gestational age at delivery, occurrence of congenital anomalies, and maternal age. Although there was a higher rate of preterm births in the placenta previa group (46.56% versus 7.27%), there was no difference in birth weights between groups after controlling for gestational age at delivery. CONCLUSION: Neonatal complications of placenta previa included preterm birth, congenital anomalies, respiratory distress syndrome, and anemia. There was no increased occurrence of fetal growth restriction.

Cohort Studies↗

Notes on the morphology of the chimpanzee and orang-utan placenta.

The placentae of 11 chimpanzees and five orang-utans were collected from Japanese zoos immediately after delivery and were examined according to the methods routinely used for the human placenta. Placenta extrachorialis (circumvallate and circummarginate placenta) occurred in 80 per cent of the specimens collected from each species. In both groups, the placental vessels were distributed predominantly in the magistral pattern, and the umbilical cord was eccentrically inserted. Subchorionic fibrin, sometimes marked, was seen in all 16 placentae, and there was a high incidence of small intervillous thrombi and deposits of intervillous fibrin. These observations, together with the histological and ultrastructural findings, confirm the previously reported similarity between the placentae of the great apes and the human placentae.

Animals↗

Histomorphometry of the human placenta in Class B diabetes mellitus.

Different morphometric parameters have been applied to the study of the morphological differences between a group of normal placentae and a group of placentae collected from Class B diabetic mothers. The placentae of the diabetics were divided in two groups based on the growth characteristics and neonatal outcome of the infants at birth. It has been shown that the placentae of the appropriate for gestational age infants were morphologically very similar to the control group except for a well-developed villous vascularization. In contrast, the placentae of the large for gestational age infants were shown to differ from the controls by having heavier placentae due mainly to a significant accumulation of non-parenchyma and a moderate increase in parenchymal tissue. Consequently, although there was significantly more villous tissue in these placentae, the surface areas of exchange between mother and fetus in terms of capillary and villous surface areas were only moderately enlarged due to a relatively lower number of villi containing non-parenchymal tissue. However, on a functional basis, despite these morphological differences, the results of this study suggest that placental function is not adversely affected in Class B diabetics, and the perinatal morbidity associated with this condition is probably the result of metabolic abnormalities present in the mother and the fetus.

Adult↗

Modification of protein kinase pattern in human placentae during gestation.

The cAMP-dependent and cAMP-independent histone kinases have been studied in the two subcellular compartments (cytosol and particulate fraction) from placentae of different gestational age. The total protein kinase activity, as well as its distribution between the two compartments, changes during the period of gestation. The total activity is significantly increased in full-term placentae. The increase is much greater for the cAMP-dependent (400 per cent), than for the cAMP-independent (270 per cent) protein kinases. It is much higher (400 per cent) in the cytosol than in the particulate fraction (170 per cent); consequently, the particulate fraction of term placentae shows a relatively lower proportion of protein kinase activity (26 per cent of the total activity) than the corresponding fraction of young placentae (37 per cent). DEAE-cellulose chromatography revealed the presence of two cAMP-dependent protein kinase peaks which correspond to Type I and Type II isoenzymes described in many mammalian tissues (Corbin, Keely and Park, 1975). The Type II isoenzyme is predominant in both first- and third-trimester placentae. The increase in protein kinase activity in term placentae is due to the selective activation of the Type II kinase only. The activity of the Type I isoenzyme remained unchanged throughout the period of gestation. The third peak eluted from the DEAE-cellulose column corresponds to a cAMP-independent sucrose-gradient ultracentrifugation into two distinct peaks similar to those already observed in several rat tissues (Toru-Delbauffe, Ohayon and Pavlovic-Hournac, 1983). The protein kinase patterns of both young and term placentae remain stable during the incubation of the tissues 'in vitro' for three hours.

Cyclic AMP↗

The placenta in leprosy.

Eighty-one placentae from women with leprosy and 17 placentae from healthy controls were subjected to a detailed macroscopic, light microscopic, ultrastructural, immunopathological, microbiological and biochemical study. The placental morphology and immunohistology were normal, and there was no morphological evidence of infection of the placenta due to M. leprae. No acid-fast bacilli or acid-fast bacillary granules were seen on light microscopy of any of the placentae from leprous women, although homogenates from two out of seven placentae from women with very active lepromatous leprosy contained acid-fast bacilli in very small numbers. The small placental size of women with leprosy, most marked in those with lepromatous leprosy, appears to be due to a decrease in placental cell size, rather than to a reduced number of cells in the placenta. It is postulated that the small placenta and reduced fetal birth weight observed in lepromatous leprosy are a consequence of depressed maternal immune reactivity.

Complement System Proteins↗