Placenta Extract Research Articles

Biochemical and functional analysis of corticotropin releasing factor purified from an aqueous extract of human placenta used as wound healer

Human placental extract constitutes of innumerable therapeutically important components mostly used in wound healing arising from the skin and burn injuries. However, there is still some bioactive present in the placental extracts yet to be characterized to better under the complex process of wound healing mediated by the placental extract. In this study, the presence of corticotropin releasing factor (CRF) in an aqueous extract of human placenta was detected and quantified by dot blot and CRF-ELISA immunoassay kit respectively. Subsequently, it was purified by immuno-affinity chromatography and quantified as 0.45±0.05μg of CRF per ml of placental extract where its molecular weight found to be 4.78kDa by MALDI-TOF. To study functional analysis of CRF, an in vitro WI-38 lung fibroblast cell scratch wound model was used which indicated proliferation, motility of cells after treatment with purified CRF. Moreover, reduction in apoptosis rate of cells during closure of wound was observed from microscopy studies and FACS analysis. Also, Antalarmin, an antagonist of CRF type 1 receptor inhibited the wound closure potency of the purified component. Faster healing of wound with an elevation of IL-6 and TGF-β during early stages of repair by placental CRF was observed on excision rat model. The process of healing was accompanied by the decrease in the level of TNF-α and IFN-γ.

Oral Administration of Glycine and Leucine Dipeptides Improves Skin Hydration and Elasticity in UVB-Irradiated Hairless Mice.

Placenta is a special organ that contains many nutrients such as growth factors, minerals, and bioactive peptides. Dipeptides of glycine and leucine are major components of porcine placenta extracts (PPE) that has been used as an alternative of human placenta extracts. In this study, we investigated whether major peptides of PPE, Glycyl-L-Leucine (Gly-Leu), L-Leucyl-Glycine (Leu-Gly), and L-Leucyl-L-Leucine (Leu-Leu), affect skin hydration and elasticity in vitro and in vivo. We found that Gly-Leu and Leu-Gly dipeptides induced the expression of transglutaminase 1 in normal human epidermal keratinocytes (NHEKs) whereas Leu-Leu dipeptides did not. Treatment with Gly-Leu or Leu-Gly significantly increased hyaluronan (HA) synthesis in NHEKs and the upregulation of hyaluronan synthase 2 (HAS2) mRNA level was confirmed. In addition, elastase activity was inhibited in NHEKs treated with Gly-Leu or Leu-Gly dipeptides. Oral administration of Gly-Leu or Leu-Gly dipeptides increased skin hydration and elasticity in UVB-irradiated hairless mice. The significant upregulation of HA in UVB-irradiated hairless mice was observed in response to oral administration of Gly-Leu or Leu-Gly. These results suggest that the major dipeptides of porcine placenta, Gly-Leu and Leu-Gly, are potentially active ingredients for skin moisturization formulations.

Коллагеногенез в ранах после криодеструкции кожи и введения криоконсервированной сыворотки кордовой крови и экстракта плаценты

The paper is devoted to the study of the effect of cryopreserved cord blood serum (CCBS) and placenta extract (PE) on collagenogenesis in regenerated tissue of skin cold wounds. Polarized light microscopy was used to study the refraction of collagen fibers with types 1 and 3 collagen in the cryogenic thermal wounds of skin after the treatment with either CCBS or PE. It was established that treatment of the animals with cold wounds by intramuscular injection of either CCBS or PE stimulated the formation and remodeling of the fibrous component of extracellular matrix. This effect was manifested in activation of the formation of type 3 collagen with its gradual replacement for type 1 collagen. At the same time, the influence of CCBS was expressed to a greater extent than that of PE. Introduction of CCBS led to an increase in the relative area of type 3 collagen to days 7 and 14 in 4.4 and 2.3 times, respectively, to day 21 it was a 2.1-fold decrease. The presence of type 1 collagens was observed to day 7, to days 14 and 21 the content of mature type 1 collagen exceeded the indices in the control group animals in 15.1 and 2.3 times, respectively. On the 21st day of observation, the relative area of immature type 1 collagen was 4.2-fold increased.Probl Cryobiol Cryomed 2017; 27(2): 133–142

Placental stem cells, organotypic culture and human placenta extract have neuroprotective activity in vitro

According to WHO, 6.7 million people die from stroke every year. The search for new neuroprotective substances remains an urgent task.The purpose of this study was to investigate the neuroprotective activity of factors of placental origin.Materials and methods. Neuroprotective activity of media conditioned with cryopreserved placenta derived mesenchymal stem cells (MSCs), organotypic culture of placenta and placental extract was studied on in vitro models of glutamate excitotoxicity in rats` neural cells. Neural cells were cultured with placental factors without glutamate treatment, before and after glutamate treatment. Neural cells` metabolic activity was assessed by MTT test.Results. Placental factors increase the MTT test indexes, prevent the toxic effect of glutamate on neural cells and promote their recovery. The thermolability of factors of placental origin and the effectiveness of various placental preparations are shown.Conclusions. Conditional media of placenta derived MSCs, organotypic culture of the placenta and human placental extract have neuroprotective effect on rats` brain cells in vitro.

Effects of Human Placenta Extract Laennec on Quality of Life and Physical Performance in Patients with Chronic Fatigue Syndrome

Objective: to evaluate the efficacy and safety of human placenta extract (HPE) Laennec infusions in treatment of patients with verified diagnosis “Chronic fatigue syndrome” (CFS). Material and methods: The study involved 38 patients with CFS, randomized into 2 groups: the experimental group (HPEL, 24 people) - patients were treated by 10 intravenous Laennec infusions, 4 ml each, 2 times/week, for 5 weeks and passive control group (CTRL, 14 pers.). Before, after, and 5 weeks follow-up treatment efficacy was evaluated by severity of chronic fatigue (Chronic Fatigue inventory), state anxiety and depression level (STAI and STDI) and Health related Quality of Life (HRQoL, questionnaire SF-36v2), exercise tolerance (cardiopulmonary exercise test with gas analysis), blood parameters. Results: The HPEL patients showed a significant reduction in index of chronic fatigue values, which was accompanied by significant decrease in situational depression, anxiety, improvements in subjective assessment of HRQoL, as well as a significant increase in exercise performance indicator values - maximum oxygen consumption, anaerobic threshold, exercise time to fatigue, normalization of the lipid “profile” after treatments and in 5 weeks follow-up. No changes in chronic fatigue index and other recorded indicators have been identified in CTRL. HPE Laennec did not cause adverse events, was well tolerated by all patients. Conclusion: The course of HPE Laennec therapy in patients with CFS reduces the severity of psychiatric symptoms experienced by chronic fatigue, decreases elevated anxiety and depression levels, improves the subjectively assessed HRQoL and objectively registered parameters of exercise performance, cardiorespiratory fitness.

Pharmacological treatment of patients with chronic fatigue syndrome

To evaluate the efficacy and safety of human placenta extract - laennec infusions in the treatment of patients with confirmed diagnosis of 'Chronic fatigue syndrome' (CFS). The study included 38 patients with CFS, randomized into 2 groups: patients of the experimental group (EG, n=24) were treated with 10 intravenous laennec infusions, 4 ml each, 2 times/week, for 5 weeks. The control group (CG) consisted of 14 patients. Treatment efficacy evaluated by the severity of chronic fatigue ('The degree of chronic fatigue' questionnaire), state anxiety, depression and anger (Spilberger test) and quality of life (SF-36v2), exercise tolerance (cardiopulmonary exercise test with gas analysis), blood parameters were assessed before, after, and 5 weeks of follow-up. The EG patients showed a significant reduction in the index of chronic fatigue, which was accompanied by the significant decrease in state depression, anxiety, improvements in subjective assessment of quality of life, as well as a significant increase in physical performance indices (maximal oxygen consumption, anaerobic threshold, load time to failure, normalization of the lipid 'profile' immediately after course of infusions and in 5 weeks follow-up). No changes in chronic fatigue index and other recorded indicators were identified in CG. Laennec did not cause side effects, was well tolerated by all patients.

Возможности гидролизата плаценты человека в комплексном лечении симптомов генитоуринарного синдрома в постменопаузе

Article is devoted an actual problem of modern gynecology - correction of the symptoms genitourinary syndrome (GUS), which has important medical and social importance. In addition to traditional hormone therapy, modern medicine has a broad range of metabolic substances, antioxidants and reparants to treat women with clinical manifestations of GUS. In this prospective study were 62 women aged up to 60 years in postmenopausal women with clinical symptoms of GUS, for the comprehensive treatment which the metabolic therapy was used the Melsmon (human placenta extract for subcutaneous injection).The results of the study demonstrated high clinical efficiency of the use of this therapy for relief of symptoms of GUS that improve the quality of life for women of postmenopausal age.

Human Placental Extract Ameliorates Structural Lung Changes Iinduced by Amiodarone in Rats.

Amiodarone is used in treatment of cardiac arrhythmias. Therapeutic use of amiodarone is limited by its side effects, including pulmonary toxicity. Human Placenta Extract (HPE) contains a variety of bio-active substances. Thus, the present study aimed to quantitatively evaluate the protective effects of HPE on the structural lung changes induced by amiodarone using stereological methods. Sprague-Dawley male rats were divided into four groups. The first, second, and third groups received no treatment, amiodarone (100 mg/kg, i.p.), and HPE (500 µL/kg, i.p.), respectively. The fourth group was treated with amiodarone + HPE. The animals' lungs were removed after 10 days. The lung volume was estimated using the Cavalieri principle on the embedded and cut tissue and corrected for shrinkage. The volume density of the parenchyma, alveolar space, and septa were estimated using point-counting method. The surface area of the alveoli, the volume-weighted means alveoli volume, and mean septum thickness were also estimated in all groups. The total volume and thickness of the alveolar septum were increased by 40 % and 28 %, respectively. However, the total volume of the alveolar space was decreased by 31 % in the amiodarone treated-rats. The mean alveolar volume was decreased by 64 % on the average in the amiodarone treated group. Yet, these changes were not detected in the amiodarone+HPE group. Moreover, RBC accumulation in the alveolar space and septa was ameliorated after HPE treatment. HPE can protect the lung tissue from the structural changes induced by amiodarone.

Preparation of a novel composite nanofiber gel-encapsulated human placental extract through layer-by-layer self-assembly.

Aqueous human placenta extract (HPE) has been previously used to treat chronic soft tissue ulcer; however, the optimal dosage of HPE has yet to be elucidated. The present study investigated a novel nanofiber gel composed through layer-by-layer (LbL) self-assembly, in which HPE was encapsulated. IKVAV, RGD, RAD16 and FGL-PA were screened and combined to produce an optimal vehicle nanofiber gel through LbL assembly. Subsequently, the aqueous HPE was encapsulated into this nanofiber at the appropriate concentration, and the morphology, particle size, drug loading efficacy, encapsulation rate, release efficiency and structure validation were detected. The encapsulation efficiency of all three HPE samples was >90%, the nanofiber gel exhibited a slow releasing profile, and the structure of HPE encapsulated in the nanofiber gel was unvaried. In conclusion, this type of novel composite nanocapsules may offer a promising delivery system for HPE.

Опыт применения гидролизата плаценты у женщин с климактерическим синдромом в перименопаузе

This article presents the results of randomized, blind, placebo-controlled prospective study in parallel groups. 40 premenopausal women with symptoms of climacteric syndrome, menstrual disordersand FSH level more than 20 mIu/ml, were recruited and randomized into 2 groups: 20 women (group 1) used placenta extract Melsmon (Japan), 2 ml (100 mg), subcutaneously, every 2nd day for 2 weeks, then 2 time a week (30 injections for 4 months in total). 20 patients (group 2) were included in the placebo group (2 ml subcutaneously, in similar regimen). After 4 months of treatment the significant decrease of modified Kupperman menopausal index, decrease of time required tofall asleep and night time awakenings number, as far as increasing of sleep duration and significant improvement of general health self-assessment were registered in both groups. The improvement of psycho-emotional symptomsand skin condition after intervention was reported only in the 1st group. 32% of women used placental extract and 5% patients from placebo group reported about menstrual episodes after period of amenorrhea, without any significant changes in endometrial thickness. Study limitations: because of the small sample size and limited observation period, more long-term trials are needed.

Вплив низькотемпературного зберігання та обробки ультразвуком плаценти на антиоксидантні властивості її екстрактів

The experimental data concerning evaluation of low temperature storage and ways of placenta extract obtaining influences on human placenta extract (HPE) antioxidant properties are provided. HPE antioxidant properties were estimated by capacity to reduce the ferric iron and ABTS + radical, to chelate ferrous ions, by phenolic compound content and the value of catalase and superoxid dismutase activity. Six-month placentae storage at –196°С has been shown not to affect HPE antioxidant activity. Moreover ultrasonic wave's application during obtaining of HPE either decreases the time of extraction or is effective factor of extracts' antioxidant properties preservation. Probl Cryobiol Cryomed 2015; 25(3):255-265

Protective effect of porcine placenta in a menopausal ovariectomized mouse

Menopause is a significant physiological phase that occurs as women's ovaries stop producing ovum and the production of estrogen declines. Human placenta and some amino acids are known to improve menopausal symptoms. In this study, we investigated that porcine placenta extract (PPE) and arginine (Arg), a main amino acid of PPE, would have estrogenic activities in ovariectomized (OVX) mice as a menopause mouse model, human breast cancer cell line (MCF-7) cells, and human osteoblast cell line (MG-63) cells. PPE or Arg significantly inhibited the body weight and increased the vagina weight compared to the OVX mice. PPE or Arg ameliorated the vaginal atrophy in the OVX mice. The levels of 17β-estradiol and the activities of alkaline phosphatase (ALP) were significantly increased by PPE or Arg in the serum of OVX mice. Trabecular bone parameters such as bone mineral density and porosity were also improved by PPE or Arg in the OVX mice. In the MCF-7 and MG-63 cells, PPE or Arg significantly increased the cell proliferation, estrogen receptor β mRNA expression, and estrogen-response elements luciferase activity. Finally, PPE or Arg increased the activations of ALP and extracellular signal-regulated kinase 1/2 in the MG-63 cells. These results indicate that PPE or Arg would have estrogenic and osteoblastic activity. Therefore, PPE or Arg may be useful as new pharmacological tools for treating menopausal symptoms including osteoporosis. Free Korean abstract: A Korean translation of this abstract is freely available at http://www.reproduction-online.org/content/150/3/173/suppl/DC1.

Enhanced Anti-inflammatory Effects of γ-irradiated Pig Placenta Extracts.

Porcine placenta extract (PPE) is known to possess anti-inflammatory properties owing to its high concentration of bioactive substances. However, the need to eliminate blood-borne infectious agents while maintaining biological efficacy raises concerns about the optimal method for sterilizing PPE. Therefore, the objective of this study was to compare the effects of the standard pressurized heat (autoclaving) method of sterilization with γ-irradiation on the anti-inflammatory effects of PPE. The anti-inflammatory actions of these two preparations of PPE were evaluated by measuring their inhibitory effects on the production of NO, the expression of iNOS protein, and the expression of iNOS, COX2, TNF-α, IL-1β, and IL-6 mRNA in lipopolysaccharide-stimulated RAW 264.7 cells. Compared with autoclaved PPE, γ-irradiated PPE showed significantly greater inhibition of NO production and iNOS protein expression, and produced a greater reduction in the expression of iNOS, COX2, TNF-α, IL-1β, and IL-6 mRNA. These results provide evidence that the sterilization process is crucial in determining the biological activity of PPE, especially its anti-inflammatory activity. Collectively, our data suggest that γ-irradiated PPE acts at the transcriptional level to effectively and potently suppresses the production of NO and the expression of pro-inflammatory cytokines.

Effects of Porcine Placenta Extract Ingestion on Ultraviolet B-induced Skin Damage in Hairless Mice

The aim of our study was to evaluate the potential benefits of an oral supplement containing porcine placenta extract (PPE) on skin parameters related to cutaneous physiology and aging. PPEs were administered orally to hairless mice for 12 wk. The effects of oral PPE administration on skin water-holding capacity and Transepidermal Water Loss (TEWL) were similar to those of oral collagen (HYCPU2) administered as a positive control. Magnified photographs and replica images showed a reduction in UVB-induced wrinkle formation after collagen and PPE treatments. PPE treatments ameliorated the thicker skin surface that results from UVB exposure, based on a histological examination of skin tissue. The groups that were orally administered PPE (0.05%, OL; 0.1%, OH group) showed significantly reduced Matrix Metaloproteinase-2 (MMP-2) mRNA expression levels compared with the UVB control (Con), by 33.5% and 35.2%, respectively. The mRNA expression of another collagen-degrading protein, MMP-9, was also significantly lower in the groups that received oral administration of PPE (especially in the OH group) than in the control group. Additionally, oral administration of PPE significantly upregulated tissue inhibitor of metalloproteinase-1 (TIMP-1) and -2 mRNA expression levels compared with expression levels in the control group (p<0.05). This indicates that orally administered PPE activated the expression of Timp-1 and -2, inhibitors of MMP, which is responsible for collagen degradation in skin. Taken together, we propose that long-term oral administration of PPE might have a beneficial effect with respect to skin photo-aging.

Protective effect of porcine placenta in a menopausal ovariectomized mouse.

Menopause is a significant physiological phase that occurs as women's ovaries stop producing ovum and the production of estrogen declines. Human placenta and some amino acids are known to improve menopausal symptoms. In this study, we investigated that porcine placenta extract (PPE) and arginine (Arg), a main amino acid of PPE, would have estrogenic activities in ovariectomized (OVX) mice as a menopause mouse model, human breast cancer cell line (MCF-7) cells, and human osteoblast cell line (MG-63) cells. PPE or Arg significantly inhibited the body weight and increased the vagina weight compared to the OVX mice. PPE or Arg ameliorated the vaginal atrophy in the OVX mice. The levels of 17β-estradiol and the activities of alkaline phosphatase (ALP) were significantly increased by PPE or Arg in the serum of OVX mice. Trabecular bone parameters such as bone mineral density and porosity were also improved by PPE or Arg in the OVX mice. In the MCF-7 and MG-63 cells, PPE or Arg significantly increased the cell proliferation, estrogen receptor β mRNA expression, and estrogen-response elements luciferase activity. Finally, PPE or Arg increased the activations of ALP and extracellular signal-regulated kinase 1/2 in the MG-63 cells. These results indicate that PPE or Arg would have estrogenic and osteoblastic activity. Therefore, PPE or Arg may be useful as new pharmacological tools for treating menopausal symptoms including osteoporosis. Free Korean abstract: A Korean translation of this abstract is freely available at http://www.reproduction-online.org/content/150/3/173/suppl/DC1.

Effect of Porcine Placenta Extract from Subcritical Water Extraction on Photodamage in Human Keratinocytes.

The objective of this study was to evaluated the photoprotective effects of porcine placenta extract (PPE) on ultraviolet B (UVB)-induced oxidative stress in human keratinocytes (HaCaT) to evaluate its functional activities as a skin food ingredient. PPE prepared by subcritical water extraction was termed SPE, and subsequently digested by enzymes to prepare E-SPE. Increased intracellular reactive oxygen species (ROS) levels (192.0%) induced by UVB were decreased by SPE and E-SPE. SPE had more effective ROS scavenging activity than E-SPE treatment. UVB treatment increased expression of tissue inhibitor of metalloproteinase 1 (TIMP-1), and this elevated expression was decreased by E-SPE treatment. High-dose treatment with E-SPE (50 and 100 µg/mL) reduced TIMP-1 expression levels of UVB-C (control) to 33.5 and 34.6%, respectively. In contrast, at low SPE doses (1 and 10 µg/mL), the treatment slightly decreased TIMP-1 expression levels to 73.3% and 71.3% of UVB-C, respectively. In conclusion, the present study demonstrated the protective effect of SPE and E-SPE against UVB damage in keratinocytes via ROS scavenging, down-regulating MMP-2 expression and up-regulating TIMP-1 expression. This highlights the potential for SPE as an ingredient in the preparation of functional food against photoaging.

Влияние криоконсервированной сыворотки кордовой крови и экстракта плаценты на заживление холодовых ран

The dynamics of planimetric and microbiological indices of cold wounds during therapy with cryopreserved cord blood serum (CCBS) and placenta extract (PE) has been studied. Cold wounds were modelled in Sphinx using the cryodevice with8.0 mmapplicator, temperature of –195°C and 60 sec exposure. Injections were started on day 3 following cryodestruction intramuscularly each other day by 0.1 ml/kg of body mass (5 injections in general). On day 7 after CCBC or PE introduction the wound area decreased 2.8 or 1.9 times, correspondingly. Wound area in non-trated animals decreased only to day 9. On day 21 the wound area in animals with PE treatment was 3.3 times smaller, than in non-treated ones, and CCBC application resulted in full epithelization of wounds. Application of CCBC and PE contributed to elimination of microbes in wounds. Number of germs in wounds of rats which were treated with CCBC or PE decreased starting from 7th day of observation (3.4 or 1.9 fold, correspondingly). On day 21 the number of germs in wounds of rats treated with PE was 8.4 times less than in control, and in case of CCBC no patogenic microflora was present. Thus, an expressed stimulation effect of CCBC and PE on wound healing was shown. The presented results offer the prospect to include the CCMA into the wound treatment protocols.Probl Cryobiol Cryomed 2015; 25(1):57-66.

Potential synergistic effects of human placental extract and minoxidil on hair growth-promoting activity in C57BL/6J mice.

Human placenta extract (HPE) has been used to alleviate tiredness and promote wound healing, and for its antiageing functions; however, it has not yet been studied for its effects on hair growth. In the present study, we evaluated the in vitro effect of HPE on hair growth by observing its actions on human dermal papilla cells (DPCs). To define how HPE promotes induction of anagen hair growth during the telogen phase, and to understand the synergistic molecular mechanisms of HPE and minoxidil (MXD) actions on hair growth. We examined the effects of HPE and MXD on C57BL6/J mice using haematoxylin and eosin staining, quantitative histomorphometry, hair growth scoring, immunohistochemistry and immunofluorescence on the dorsal skins of C57BL/6J mice. We found that HPE synergistically augmented the effects of MXD, a promoter of hair growth. In particular, histomorphometric analysis data indicated that subcutaneous injection of HPE induced an earlier anagen phase and prolonged the anagen phase. It also stimulated increases in both the number and size of hair follicles in groups treated with HPE alone and HPE+MXD. From our data, we conclude that HPE increases β-catenin and Wnt3a expression levels. Overall, our findings suggest that HPE in combination with MXD has hair growth-promoting activity and is a potential novel therapeutic treatment for alopecia or baldness in humans.

A novel biomarker for anti-androgenic activity in placenta reveals risks of urogenital malformations.

It has been hypothesized that the rise in male reproductive disorders over recent decades may at least be partially attributable to environmental factors, including chemical exposures, but observed associations with single chemicals were rather weak. The aim of this case-control study was to explore the relationship between exposure to mixtures of (anti-)androgenic chemicals during pregnancy and the risk of cryptorchidism and/or hypospadias in offspring, using the total effective xenobiotic burden of anti-androgens (TEXB-AA) as a biomarker. A subsample of 29 cases (16 of cryptorchidism, 12 of hypospadias, and one of both disorders) and 60 healthy controls was nested in a cohort of male newborns recruited between October 2000 and July 2002. The (anti-)androgenic activity of placenta samples collected at delivery was assessed using TEXB-AA biomarker, combined with a bioassay-directed fractionation protocol that separated endogenous hormones from most (anti-)androgenic chemicals by normal-phase HPLC. The bioassay measures the androgen-induced luciferase activity and the inhibition of this pathway by (anti-)androgens. First, we collected 27 HPLC fractions in each placenta extract, which were all tested in the bioassay. The multivariable statistical analyses indicated a statistically significant positive dose-response association between the potent anti-androgenic activity of the HPLC fraction collected during minutes 1-2 (F2) and the risk of malformations (odds ratio: 2.33, 95% CI: 1.04-5.23). This study represents a novel approach for the estimation of combined effects of the total anti-androgenic load and the associations suggest an effect of environmental pollutants on the development of fetal reproductive tract.Free Spanish abstract: A Spanish translation of this abstract is freely available at http://www.reproduction-online.org/content/149/6/605/suppl/DC1.

271-POS

Objectives In our quest to contribute to the definition of a molecular preeclamptic signature we encountered acid beta glucosidase (GBA, encoding for the enzyme glucocerebrosidase) as a gene that is up regulated in preeclamptic placentas. GBA deficiency causes Gaucher’s disease, a lysosomal storage disease. GBA hydrolyzes glucosylceramide to free glucose and ceramide. Ceramide is a bioactive signaling molecule involved in the regulation of cell movement, differentiation, survival and apoptosis. Purified GBA from placenta extracts was used to treat Gaucher patients with enzyme replacement therapy before the recombinant protein became available. The reason for the abundant expression in placenta and its role in the (patho) physiology of pregnancy is a complete enigma. Methods We used multiple molecular techniques such as real time polymerase chain reaction, a lysosomal enzyme activity assay, 5′ race to detect alternatively spliced variants, transfection of different variants in HEK-293 cells and Western blot analysis, in situ hybridization and immunofluorescence assays to determine cellular localization and micro-array analysis to determine correlation of GBA expression to expression levels of other genes in placenta. Results GBA is up regulated and there is increased lysosomal activity in the preeclamptic placenta. In placenta multiple variants are present but only the full-length GBA protein possesses classical lysosomal activity indicating its role in the lysosomal pathway in placenta. GBA is located in the syncytiotrophoblast layer of the placenta and immunofluorescence is suggestive of lysosomal localization. 158 genes correlate either positively or negatively with GBA expression. Gene enrichment analysis confirms the lysosomal pathway in placenta. Conclusions The increased levels of GBA are most probably a result of the increased cell turnover in the preeclamptic placenta. However since we expect higher levels of ceramide in those cases it may also put ceramide forward as a novel etiological factor in the pathophysiology of preeclampsia. Disclosures J.M. Jebbink: None. R.G. Boot: None. R. Keijser: None. P.D. Moerland: None. J. Aten: None. G.J. Veenboer: None. M. van Wely: None. M. Buimer: None. E. Ver Loren van Themaat: None. J.M. Aerts: None. J.A. van der Post: None. G.B. Afink: None. C. Ris-Stalpers: None.