Human Placental Extracts Research Articles

The role of KNDy neurons in human reproductive health.

In the early 2000s, metastin, an endogenous ligand for G protein-coupled receptor 54 (GPR54), was discovered in human placental extracts. In 2003, GPR54 receptor mutations were found in a family with congenital hypogonadotropic hypogonadism. Metastin was subsequently renamed kisspeptin after its coding gene, Kiss1. Since then, studies in mice and other animals have revealed that kisspeptin is located at the apex of the hypothalamic-pituitary-gonadal axis and regulates reproductive functions by modulating gonadotropin-releasing hormone (GnRH). In rodents, kisspeptin (Kiss1) neurons localize to two regions, the hypothalamic arcuate nucleus (ARC) and the anteroventral periventricular nucleus (AVPV). ARC Kiss1 neurons co-express neurokinin B (NKB) and dynorphin and are thus termed KNDy neurons. Kiss1 neurons in humans are concentrated in the infundibular nucleus (equivalent to the ARC), with few Kiss1 neurons localized to the preoptic area (equivalent to the AVPV), and the mechanisms underlying GnRH surge secretion in humans are poorly understood. However, peripheral administration of kisspeptin to humans promotes gonadotropin secretion, and administration of kisspeptin to patients with hypothalamic amenorrhea or congenital hypogonadotropic hypogonadism restores the pulsatile secretion of GnRH/luteinizing hormone. Thus, kisspeptin undoubtedly plays an important role in reproductive function in humans. Studies are currently underway to develop kisspeptin receptor agonists or antagonists for clinical application. Modification of KNDy neurons by NKB agonists/antagonists is also being attempted to develop therapeutic agents for various menstrual abnormalities, including polycystic ovary syndrome and menopausal hot flashes. Here, we review the role of kisspeptin in humans and its clinical applications.

Clinical evaluation of gingival healing following gingivectomy with application of human placental extracts (placentrex gel)

Clinical evaluation of gingival healing following gingivectomy with application of human placental extracts (placentrex gel)

Highly elastic 3D-printed gelatin/HA/placental-extract scaffolds for bone tissue engineering.

Bioengineering scaffolds have been improved to achieve efficient regeneration of various damaged tissues. In this study, we attempted to fabricate mechanically and biologically activated 3D printed scaffold in which porous gelatin/hydroxyapatite (G/H) as a matrix material provided outstanding mechanical properties with recoverable behavior, and human placental extracts (hPE) embedded in the scaffold were used as bioactive components.Methods: Various cell types (human adipose-derived stem cells; hASCs, pre-osteoblast; MC3T3-E1, human endothelial cell line; EA.hy926, and human dermal fibroblast; hDFs) were used to assess the effect of the hPE on cellular responses. High weight fraction (~ 70 wt%) of hydroxyapatite (HA) in a gelatin solution supplemented with glycerol was used for the G/H scaffold fabrication, and the scaffolds were immersed in hPE for the embedding (G/H/hPE scaffold). The osteogenic abilities of the scaffolds were investigated in cultured cells (hASCs) assaying for ALP activity and expression of osteogenic genes. For the in vivo test, the G/H and G/H/hPE scaffolds were implanted in the rat mastoid obliteration model.Results: The G/H/hPE scaffold presented unique elastic recoverable properties, which are important for efficient usage of implantable scaffolds. The effects of G/H and G/H/hPE scaffold on various in vitro cell-activities including non-toxicity, biocompatibility, and cell proliferation were investigated. The in vitro results indicated that proliferation (G/H = 351.1 ± 13.3%, G/H/hPE = 430.9 ± 8.7% at day 14) and expression of osteogenic markers (ALP: 3.4-fold, Runx2: 3.9-fold, BMP2: 1.7-fold, OPN: 2.4-fold, and OCN: 4.8-fold at day 21) of hASCs grown in the G/H/hPE scaffold were significantly enhanced compared with that in cells grown in the G/H scaffold. In addition, bone formation was also observed in an in vivo model using rat mastoid obliteration.Conclusion: In vitro and in vivo results suggested that the G/H/hPE scaffold is a potential candidate for use in bone tissue engineering.

Comparative Evaluation to Assess the Effect of SRP With or Without Human Placental Extracts as Local Drug Delivery in Treatment of Localized Periodontal Pocket- A Randomized Controlled Clinical Trial

Background: Periodontal disease is one of the most prevalent global chronic disorder. Pathology affecting the structure surrounding teeth results in inflammation initiated by bacterial aggregation & alteration in their profile. Conventional periodontal therapeutics has focused on the control of etiologic agents, thereby promoting healing & repair of tissues. Delivery of therapeutic agents into the local milieu act as drug reservoirs which could alter pathogenic flora & promote its repair & wound healing. Aim & Objective: In an effort to develop a novel therapy, the present study aims to compare clinical soft tissue parameters around periodontal pockets treated with & without human placental extracts delivered locally. Materials & Method: In 10 patients of chronic periodontitis, bilateral localized periodontal pockets of 4-6 mm depth were included. Each site was randomly allocated to group 1 & group 2,where in group 1, scaling & root planing( SRP) was done while in group 2,Placentrex Gel (Human placental extracts) adsorbed on absorbable gelatin matrix (Abgel) used as a vehicle was delivered as an adjunct to SRP . Clinical parameters were recorded & re- evaluated after one month for both the treatment groups . Statistical analysis was carried out to evaluate the effect of Placentrex gel as an adjunct to SRP in treatment of periodontal pockets, Mann Whitney & Paired t test were done. Results: There was a statistically significant improvement in clinical parameters with notable difference in probing depth reduction & gain of clinical attachment level in the treatment group subjected to SRP & Placental extract delivery. Conclusion: Clinical variables showed a greater efficacy of SRP & adjunctive use of placental extracts as compared to conventional treatment by SRP thereby underlying placental extracts usage in the management of periodontal disease condition

Application of injection Kenacort, intradermal route in oral submucous fibrosis

<p class="abstract"><strong>Background:</strong> Oral submucous fibrosis is a potentially pre-malignant disease, that results in progressive juxta-epithelial fibrosis of oral soft tissues, resulting in increased loss of tissue mobility, marked rigidity and inability to open the mouth. Actual treatment includes iron, multi vitamins, lycopene, pentoxifyline, steroid injections and human placental extracts. Currently available treatment with intradermal injection of Kenacort with hyaluronidase is effective to some extent.</p><p class="abstract"><strong>Methods:</strong> This study was conducted at Basaveshwara Medical College and Hospital, Research Centre, Chitradurga, Karnataka, in the Otorhinolaryngology Department from February 2019 to August 2019 for 6 months duration. A total of 40 patients were included in this study. Mouth opening was recorded from baseline to 6 weeks. Cases were followed up for 6 months thereafter. Patients with positive history of chewing of betel-nuts, pan, gutkha and age from 18-50 years males and females were included in this study. Patients undergoing any surgery, allergic conditions, age more than 50 years were excluded. Mouth opening was assessed by objective type and subjective type.</p><p class="abstract"><strong>Results:</strong> There was significant increase in mouth opening in patients after administration of intra-dermal Kenacort injection and oral lycopene. The results were statistically significant and patients responded better and p value <0.001.</p><p class="abstract"><strong>Conclusions:</strong> Management of moderate oral submucous fibrosis should include counselling of patients along with oral lycopene with intradermal injection of Kenacort with hyaluronidase, is highly efficacious and cost- effective in improving the mouth opening and reducing other symptoms in patients with OSMF, whereas advanced stages should be treated surgically.</p>

The role of AKT and FOXO3 in preventing ovarian toxicity induced by cyclophosphamide.

Cyclophosphamide (CTX) has immunosuppressive effects and has been wildly used as one anti-cancer drug in clinical. Significant toxicity has been noticed particularly in the reproductive system. CTX promotes the maturation of ovarian follicles, decreases follicular reserve, and ultimately lead to ovarian failure or even premature ovarian failure (POF). The placental extract (HPE) has been shown to have some beneficial impact on reproductive system; however, little is known regarding to the effect of HPE on protecting CTX-induced ovarian injury and the mechanism involved. Whether human placental extracts (HPE) has a protective effect on CTX-induced toxicity on ovarian was studied by using a CTX-induced ovarian injury animal model. The effects of HEP on histopathology, the number of atretic follicles, the weight of the ovary, serum hormone levels, and apoptosis in granulosa cells were studied in mice with CTX or control vehicle. Our results have demonstrated that HPE inhibited p-Rictor, reduced the expression of Bad, Bax and PPAR, and activated Akt and Foxo3a (increased their phosphorylation). Mice treated with HPE showed higher ovarian weight, lower number of atretic follicles, higher serum levels of the hormones E2 and progesterone, and lower apoptosis and serum levels of LH and FSH in granulosa cells, than that in the control animal group. Our data show that ovarian injury can be attenuated by HPE. HPE likely protects follicular granulosa cells from undergoing significant apoptosis and reduce atresia follicle formation, therefore, alleviates CTX-induced ovarian injury.

Human Placental Extracts Improve Ovarian Function by Reducing Follicular Atresia in Mice With CTX-Induced Premature Ovarian Failure

The details of the pathogenic mechanisms underlying premature ovarian failure (POF) remain unknown. Accumulating evidence suggests that primordial follicle inactivity, disorders affecting follicular survival and growth and follicular atresia may affect an individual’s susceptibility to POF. The Rictor/mTORC2/Akt/Foxo3a pathway plays a central role in cytoskeletal construction and follicle survival. As a stronger alkylating agent that exerts immunosuppressive effects, cyclophosphamide (CTX) is widely used in clinical practice, especially in cancer. However, it also has significant reproductive toxicity. CTX accelerates the development of ovarian follicles into mature follicles, resulting in a decreased follicular reserve and ultimately leading to ovarian failure or even POF. We have sought to research effective methods to reduce the damage caused by CTX. Here, we investigated the protective role of human placental extracts on CTX-induced ovarian injury in mice. We describe the effects of HEP on histopathology, the number of atretic follicles, the weight of the ovary, serum hormone levels and apoptosis in granulosa cells. Our data show that ovarian injury can be effectively attenuated by HPE administration. Ovarian weight was higher, the number of atretic follicles was lower, the serum levels of the hormones E2 and P were higher, and the rate of apoptosis and the serum levels of the hormones LH and FSH were lower in granulosa cells in mice treated with HPE for 2 weeks than in the control group. A t the molecular level, our results demonstrated that HPE can be used to inhibit the expression of p-Rictor, Bad, Bax and PPAR and activate the expression of p-Akt and p-Foxo3a, thus preventing follicular granulosa cells from undergoing a higher rate of apoptosis and blocking atresia follicle formation. These effects alleviated CTX-induced ovarian injury by affecting the Rictor/mTORC2/Akt/Foxo3a signalling pathway.

Indolizine-Based Scaffolds as Efficient and Versatile Tools: Application to the Synthesis of Biotin-Tagged Antiangiogenic Drugs.

We describe the design and optimization of polyfunctional scaffolds based on a fluorescent indolizine core derivatized with various orthogonal groups (amines, esters, oximes, alkynes, etc.). To show one application as tools in biology, the scaffold was used to prepare drug–biotin conjugates that were then immobilized onto avidin-agarose for affinity chromatography. More specifically, the antiangiogenic drug COB223, whose mechanism of action remained unclear, was chosen as a proof-of-concept drug. The drug-selective discrimination of proteins observed after elution of the cell lysates through the affinity columns, functionalized either with the biologically active COB223 or a structurally related inactive analogue (COB236), is a clear indication that the presence of the indolizine core does not limit drug–protein interaction and confirms the usefulness of the indolizine scaffold. Furthermore, the separation of COB223-interacting proteins from human placental extracts unveiled unanticipated protein targets belonging to the family of regulatory RNA-binding proteins, which opens the way to new hypotheses on the mode of action of this antiangiogenic drug.

Components of human placental extract and its protective effect to rat from D-GalN induced acute liver injury

Objective: To evaluate the effect of human placental extracts (HPE) on the protection from acute liver injury (ALI) induced by D-GalN and analyze the components of HPE. Methods: (1)Fourty male mice were randomly divided into five groups (Blank, Model, MgIG, HPE and HPE+ MgIG) for the ALI model and treatments.The serum alanine aminotransferase (ALT) and aspartate transaminase (AST) were determined by biochemical assays.Nitric monoxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant capacity (T-AOC) in serum and hepatic tissue were detected by assay kits.The extent of liver damage was evaluated by histological examination.(2)Relative molecular mass of HPE was determined by SDS-PAGE.(3) Component identification was performed by using LCMS-TOF.(4)Selected functional molecules in HPE were detected by protein array. Results: (1) A lower level of NO and MDA and a higher SOD and T-AOC were observed in rats treated with HPE compared to the non-treated rats in an acute liver failure disease model.(2) The size of HPE was about 1 200-4 600 by electrophores.(3) 7 peaks of HPE were identified, including uracil, hypoxanthine, tyrosine, phenylalanine, tryptophan, xanthine and thymine.(4) Comparable high concentrations of TGF-β, IGF-1, IL-9, IL-29 and TNF-α of HPE were revealed by protein array. Conclusions: (1) HPE protects rat from liver damage induced by D-GalN. (2) HPE contains Uracil, hypoxanthine, xanthine, thymine, and functional proteins as TGF-β, IGF-1, IL-9, IL-29 and TNF-α.

Evaluation of Collagen Type-1 Production and Anti-Inflammatory Activities of Human Placental Extracts in Human Gingival Fibroblasts

Evaluation of Collagen Type-1 Production and Anti-Inflammatory Activities of Human Placental Extracts in Human Gingival Fibroblasts

Properties of aqueous-saline human placental extracts and their fractions after storage of placenta at various subzero temperatures

Objective: In this study we analyzed the influence of low temperature storage of placental tissue on the effect of obtained aqueous-saline placental extracts and their extract fractions on the state of membranes and cytosol of erythrocytes. Methods: Fractions of human placenta extract (HPE) were obtained with gel-chromatography method. Spontaneous hemolysis of erythrocytes was measured spectrophotometrically by free hemoglobin content in supernatant at 543 nm wavelength. Osmotic fragility (resistance) of erythrocytes was assessed by the level of hemolysis in 0.45% NaCl solution. Low-pH resistance of erythrocytes was evaluated by the time of 50% hemolysis in sodium-phosphate-citrate buffer (pH 3.8), calculating the data from kinetic curve of the change of optical density at 700 nm. Electron paramagnetic resonance (EPR) spin probe method was applied for analysis of cytosol dynamic state. Results: We recorded that low temperature storage of placental tissue allows decreasing membranotropic effect, which was inherent to certain aqueous-saline placental extracts and some of their fractions. At the same time, storage of placental tissue at both 20 С and 196 С does not influence the ability of HPE to decrease erythrocyte osmotic fragility. Erythrocytes exposed with HPE derived from placenta stored for 6 months at 20 С displayed decrease of low-pH resistance. This effect was inherent not only to the whole placental extract, but also to its certain fractions, especially those with molecular weight below 5 kDa. Conclusions: Storage of placental tissue at 196 С seems to be advantageous for preservation of studied properties of placental aqueous-saline extract in comparison to storage at 20 С.

ヒト胎盤抽出物の肝癌細胞増殖抑制及び正常細胞障害抑制

ヒト胎盤抽出物の肝癌細胞増殖抑制及び正常細胞障害抑制

Neuroprotective effect of human placental extract on hypoxic–ischemic brain injury in neonatal rats

We investigated the neuroprotective effects of human placental extracts (HPE) and the effects of HPE on recovery of cognitive and behavioral function on hypoxic–ischemic brain injury in the newborn rat. The right common carotid arteries of 7-day-old rats were coagulated, and rats were then exposed to 8% oxygen. Immediately before and again at three times after the hypoxia–ischemia (pre-treatment group), and immediately after and three times again after hypoxia–ischemia (post-treatment group), the rats were intraperitoneally injected with HPE (0.1, 0.25, or 0.5mL/10g/dose). No-treatment rats received saline only. On postnatal day 12, brains were removed and gross morphological damage was evaluated. To quantify the severity of brain injury, bilateral cross-sectional areas of the anterior commissural and posterior hippocampal levels were analyzed with NIH Image. Assessments of the open field activity levels at 2, 4, 6 and 8week and, the Morris water maze test at 8weeks after hypoxia–ischemia were carried out according to standard methods. HPE pre-treatment decreased the incidence of liquefactive cerebral infarction, at an optimally neuroprotective dose of 0.5mL/10g/dose (P<0.05). In the Morris water maze test, the group injected with HPE at 0.5mL/10g/dose concentration showed shorter escape latencies than the no-treatment group (P<0.05). These findings support a protective effect of the HPE treatment on neuronal integrity and cognitive function following hypoxic–ischemic brain injury. Injected at an appropriate dose prior to exposure, HPE may significantly reduce or prevent hypoxic–ischemic injury in the immature brain.

Membrane-active antimicrobial peptides and human placental lysosomal extracts are highly active against mycobacteria

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, manifests discreet strategies to subvert host immune responses, which enable the pathogen to survive and multiply inside the macrophages. This problem is further worsened by the emergence of multidrug resistant mycobacterial strains, which make most of the anti-tuberculous drugs ineffective. It is thus imperative to search for and design better therapeutic strategies, including employment of new antibiotics. Recently, naturally produced antimicrobial molecules such as enzymes, peptides and their synthetic analogs have emerged as compounds with potentially significant therapeutical applications. Although, many antimicrobial peptides have been identified only very few of them have been tested against mycobacteria. A major limitation in using peptides as therapeutics is their sensitivity to enzymatic degradation or inactivity under certain physiological conditions such as relatively high salt concentration. Here, we show that NK-2, a peptide representing the cationic core region of the lymphocytic effector protein NK-lysin, and Ci-MAM-A24, a synthetic salt-tolerant peptide derived from immune cells of Ciona intestinalis, efficiently kill Mycobacterium smegmatis and Mycobacterium bovis-BCG. In addition, NK-2 and Ci-MAM-A24 showed a synergistic killing effect against M. smegmatis, no cytotoxic effect on mouse macrophages at bactericidal concentrations, and were even found to kill mycobacteria residing inside the macrophages. We also show that human placental lysosomal contents exert potent killing effect against mycobacteria under acidic and reducing growth conditions. Electron microscopic studies demonstrate that the lysosomal extract disintegrate bacterial cell membrane resulting in killing of mycobacteria.

The Effect of Human Placenta Extract in a Wound Healing Model

Human placenta had been used on wound healing such as burns, chronic ulcers, and skin defects. Recently, human placenta has been widely used in the form of human placental extracts (HPE) by clinical field. However, it is unclear what the effect of HPE is on wound healing. We studied the effect and mechanism of HPE on wound healing.In this study, 10 mice (imprinting control region mice, 5 week old males, 30 g) were divided into an experimental group and a control group. An 8-mm diameter single full-thickness skin defect was made on the back by skin punch biopsy. At least 2.0 x 10 mL/30 g HPE was injected into the boundaries of the wound. Wound size measurements were taken by digital image every 3 days over 2 weeks. Hematoxylin and eosin (H and E), transforming growth factor beta (TGF-beta), vascular endothelial growth factor (VEGF), and CD31+ immunohistochemical stains were performed on the 6th and 14th day.The experimental group showed acceleration in the decrease of wound size compared with the control group from the third day to the ninth day. TGF-beta on the 6th day showed a statistically significant increase in the experimental group. VEGF on the 14th day showed a statistically significant increase in the experimental group. CD31+ was increased in the experimental group as wound healing progressed, but this increase was not statistically significant. The total number of vessels increased in the experimental group, but this was not statistically significant.We conclude that administering HPE directly to a wound margin promoted wound healing. This mechanism appears to be related to an increase in TGF-beta in the early phase of wound healing and VEGF in the late phase.

Glutamate is the chemotaxis-inducing factor in placental extracts

Human placental extracts are known to help wound healing. Rapid migration of neutrophils to the wound site is a prerequisite to the wound healing process. Gel filtration analysis of heat-treated placental extract gave the initial cue to the small nature of the migration promoting factor of the extract. HPLC analysis of the extract revealed glutamate to be the predominant free amino acid. Our studies show that glutamate at an optimum concentration of 8 microM induced phenotypic neutrophil chemotaxis, as seen in the time lapse and transwell assays. Glutamate was also found to induce chemokinesis of the neutrophil, though the stimulation of chemotaxis was more pronounced. The glutamate induced chemotaxis was accompanied by polarization of the actin cytoskeleton, and by polymerization of F-actin. These data indicate that glutamate has a strong chemotactic functionality in the neutrophil, which could be of interest both therapeutically and in further investigation of the molecular basis of chemotaxis.

Glutamate is the chemotaxis-inducing factor in placental extracts

Human placental extracts are known to help wound healing. Rapid migration of neutrophils to the wound site is a prerequisite to the wound healing process. Gel filtration analysis of heat-treated placental extract gave the initial cue to the small nature of the migration promoting factor of the extract. HPLC analysis of the extract revealed glutamate to be the predominant free amino acid. Our studies show that glutamate at an optimum concentration of 8 muM induced phenotypic neutrophil chemotaxis, as seen in the time lapse- and transwell assays. Glutamate was also found to induce chemokinesis of the neutrophil, though the stimulation of chemotaxis was more pronounced. The glutamate induced chemotaxis was accompanied by polarization of the actin cytoskeleton, and by polymerization of F-actin. These data indicate that glutamate has a strong chemotactic functionality in the neutrophil, which could be of interest both therapeutically and in further investigation of the molecular basis of chemotaxis.

Time- and Dose-Dependent Effects of Roundup on Human Embryonic and Placental Cells

Roundup is the major herbicide used worldwide, in particular on genetically modified plants that have been designed to tolerate it. We have tested the toxicity and endocrine disruption potential of Roundup (Bioforce on human embryonic 293 and placental-derived JEG3 cells, but also on normal human placenta and equine testis. The cell lines have proven to be suitable to estimate hormonal activity and toxicity of pollutants. The median lethal dose (LD(50)) of Roundup with embryonic cells is 0.3% within 1 h in serum-free medium, and it decreases to reach 0.06% (containing among other compounds 1.27 mM glyphosate) after 72 h in the presence of serum. In these conditions, the embryonic cells appear to be 2-4 times more sensitive than the placental ones. In all instances, Roundup (generally used in agriculture at 1-2%, i.e., with 21-42 mM glyphosate) is more efficient than its active ingredient, glyphosate, suggesting a synergistic effect provoked by the adjuvants present in Roundup. We demonstrated that serum-free cultures, even on a short-term basis (1 h), reveal the xenobiotic impacts that are visible 1-2 days later in serum. We also document at lower non-overtly toxic doses, from 0.01% (with 210 microM glyphosate) in 24 h, that Roundup is an aromatase disruptor. The direct inhibition is temperature-dependent and is confirmed in different tissues and species (cell lines from placenta or embryonic kidney, equine testicular, or human fresh placental extracts). Furthermore, glyphosate acts directly as a partial inactivator on microsomal aromatase, independently of its acidity, and in a dose-dependent manner. The cytotoxic, and potentially endocrine-disrupting effects of Roundup are thus amplified with time. Taken together, these data suggest that Roundup exposure may affect human reproduction and fetal development in case of contamination. Chemical mixtures in formulations appear to be underestimated regarding their toxic or hormonal impact.

Discordant expression of pro-B-type and pro-C-type natriuretic peptide in newborn infants of mothers with type 1 diabetes

Background Maternal diabetes increases the risk of hypertrophic cardiomyopathy in the fetus. As signaling via the C-type natriuretic peptide (CNP) specific receptor protects against cardiac hypertrophy, we examined whether maternal type 1 diabetes affects the plasma concentrations of proCNP-derived peptides in newborn infants. Methods Plasma concentrations of proCNP-derived peptides were measured in umbilical cord plasma and human placental tissue extracts using sequence-specific radioimmunoassays raised against N-terminal and C-terminal proCNP regions, respectively. Results The median proCNP concentrations were similar in umbilical cord plasma from pregnant women with and without type 1 diabetes (17 pmol/L vs. 19 pmol/L, P not significant) and did not correlate with the proBNP concentrations in the same samples. However, the molar ratio between the proCNP and the CNP peptide was increased in umbilical cord plasma compared to adult plasma (4.6 vs. 1.1), which parallels our earlier findings for proBNP and BNP peptides. Conclusions There is a discordant expression of CNP and BNP peptides in newborn infants of mothers with diabetes. Moreover, fetal metabolism of proCNP and CNP appears to differ from healthy adults. The precise mechanism underlying these differences warrants further investigation.

Endothelial and lipoprotein lipases in human and mouse placenta

Placenta expresses various lipase activities. However, a detailed characterization of the involved genes and proteins is lacking. In this study, we compared the expression of endothelial lipase (EL) and LPL in human term placenta. When placental protein extracts were separated by heparin-Sepharose affinity chromatography, the EL protein eluted as a single peak without detectable phospholipid or triglyceride (TG) lipase activity. The major portion of LPL protein eluted slightly after EL. This peak also had no lipase activity and most likely contained monomeric LPL. Fractions eluting at a higher NaCl concentration contained small amounts of LPL protein (most likely dimeric LPL) and had substantial TG lipase activity. In situ hybridization studies showed EL mRNA expression in syncytiotrophoblasts and endothelial cells and LPL mRNA in syncytiotrophoblasts. In contrast, immunohistochemistry showed EL and LPL protein associated with both cell types. In mouse placentas, lack of LPL expression resulted in increased EL mRNA expression. These results suggest that the cellular expression of EL and LPL in human placenta is different. Nevertheless, the two lipases might have overlapping functions in the mouse placenta. Our data also suggest that the major portions of both proteins are stored in an inactive form in human term placenta.