{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:42:10Z","timestamp":1760240530373,"version":"build-2065373602"},"reference-count":41,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2019,7,12]],"date-time":"2019-07-12T00:00:00Z","timestamp":1562889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2015R1C1A1A02037172","NRF-2017R1A2B3009574"],"award-info":[{"award-number":["NRF-2015R1C1A1A02037172","NRF-2017R1A2B3009574"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Spontaneous abortion represents a common form of embryonic loss caused by early pregnancy failure. In the present study, we investigated the prophylactic effects of bee venom phospholipase A2 (bvPLA2), a regulatory T cell (Treg) inducer, on a lipopolysaccharide (LPS)-induced abortion mouse model. Fetal loss, including viable implants, the fetal resorption rate, and the fetal weight, were measured after LPS and bvPLA2 treatment. The levels of serum and tissue inflammatory cytokines were determined. To investigate the involvement of the Treg population in bvPLA2-mediated protection against fetal loss, the effect of Treg depletion was evaluated following bvPLA2 and LPS treatment. The results clearly revealed that bvPLA2 can prevent fetal loss accompanied by growth restriction in the remaining viable fetus. When the LPS-induced abortion mice were treated with bvPLA2, Treg cells were significantly increased compared with those in the non-pregnant, PBS, and LPS groups. After LPS injection, the levels of proinflammatory cytokines were markedly increased compared with those in the PBS mouse group, while bvPLA2 treatment showed significantly decreased TNF-\u03b1 and IFN-\u03b3 expression compared with that in the LPS group. The protective effects of bvPLA2 treatment were not detected in Treg-depleted abortion-prone mice. These findings suggest that bvPLA2 has protective effects in the LPS-induced abortion mouse model by regulating Treg populations.<\/jats:p>","DOI":"10.3390\/toxins11070404","type":"journal-article","created":{"date-parts":[[2019,7,12]],"date-time":"2019-07-12T11:49:38Z","timestamp":1562932178000},"page":"404","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Prophylactic Effects of Bee Venom Phospholipase A2 in Lipopolysaccharide-Induced Pregnancy Loss"],"prefix":"10.3390","volume":"11","author":[{"given":"Hyunjung","family":"Baek","sequence":"first","affiliation":[{"name":"Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul 02453, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"HyeJin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul 02453, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jong Hoon","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul 02453, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na-Hoon","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Clinical Korean Medicine, Graduate School, Kyung Hee University, Seoul 02453, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinwook","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Clinical Korean Medicine, Graduate School, Kyung Hee University, Seoul 02453, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0299-3582","authenticated-orcid":false,"given":"Hyunsu","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul 02453, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9179-0797","authenticated-orcid":false,"given":"Deok-Sang","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Clinical Korean Medicine, Graduate School, Kyung Hee University, Seoul 02453, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1111\/j.1600-0897.2010.00852.x","article-title":"Th1\/Th2\/Th17 and regulatory T-cell paradigm in pregnancy","volume":"63","author":"Saito","year":"2010","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/S0952-7915(00)00170-9","article-title":"Tolerance to the foeto-placental \u2018graft\u2019: Ten ways to support a child for nine months","volume":"12","author":"Thellin","year":"2000","journal-title":"Curr. Opin. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1038\/ni1317","article-title":"Mother\u2019s little helpers: Mechanisms of maternal-fetal tolerance","volume":"7","author":"Trowsdale","year":"2006","journal-title":"Nat. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S0165-0378(02)00005-0","article-title":"Decidual natural killer cells: Key regulators of placental development (a review)","volume":"57","author":"Croy","year":"2002","journal-title":"J. Reprod. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1053\/beog.2000.0123","article-title":"Epidemiology and the medical causes of miscarriage","volume":"14","author":"Regan","year":"2000","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1053\/beog.2000.0124","article-title":"Genetic aspects of miscarriage","volume":"14","author":"Goddijn","year":"2000","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1055\/s-2006-931797","article-title":"Genetics of recurrent pregnancy loss","volume":"24","author":"Sierra","year":"2006","journal-title":"Semin. Reprod. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1159\/000320546","article-title":"Localization of cathepsins D and B at the maternal-fetal interface and the invasiveness of the trophoblast during the postimplantation period in the mouse","volume":"193","author":"Hoshida","year":"2011","journal-title":"Cells Tissues Organs"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.molimm.2012.08.025","article-title":"Reproductive immunology","volume":"55","author":"Christiansen","year":"2013","journal-title":"Mol. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1111\/j.1447-0756.2009.01079.x","article-title":"Recurrent pregnancy loss: A disease of inflammation and coagulation","volume":"35","author":"Yang","year":"2009","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.jri.2016.04.288","article-title":"The importance of being a regulatory T cell in pregnancy","volume":"116","author":"Clark","year":"2016","journal-title":"J. Reprod. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1093\/molehr\/gah044","article-title":"Decidual and peripheral blood CD4+CD25+ regulatory T cells in early pregnancy subjects and spontaneous abortion cases","volume":"10","author":"Sasaki","year":"2004","journal-title":"Mol. Hum. Reprod."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.jri.2013.03.006","article-title":"Seminal plasma peptides may determine maternal immune response that alters success or failure of pregnancy in the abortion-prone CBAxDBA\/2 model","volume":"99","author":"Clark","year":"2013","journal-title":"J. Reprod. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"158","DOI":"10.3389\/fimmu.2013.00158","article-title":"Control of uterine microenvironment by foxp3(+) cells facilitates embryo implantation","volume":"4","author":"Teles","year":"2013","journal-title":"Front. Immunol."},{"key":"ref_15","first-page":"197","article-title":"Clinical randomized study of bee-sting therapy for rheumatoid arthritis","volume":"33","author":"Liu","year":"2008","journal-title":"Zhen Ci Yan Jiu"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Kim, H., Keum, D.J., Kwak, J., Chung, H.S., and Bae, H. (2014). Bee venom phospholipase A2 protects against acetaminophen-induced acute liver injury by modulating regulatory T cells and IL-10 in mice. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0114726"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4853","DOI":"10.4049\/jimmunol.1500386","article-title":"Bee Venom Phospholipase A2, a Novel Foxp3+ Regulatory T Cell Inducer, Protects Dopaminergic Neurons by Modulating Neuroinflammatory Responses in a Mouse Model of Parkinson\u2019s Disease","volume":"195","author":"Chung","year":"2015","journal-title":"J. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1095\/biolreprod.112.102293","article-title":"DBA-lectin reactivity defines mouse uterine natural killer cell subsets with biased gene expression","volume":"87","author":"Chen","year":"2012","journal-title":"Biol. Reprod."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1016\/j.placenta.2009.08.011","article-title":"DBA-lectin reactivity defines natural killer cells that have homed to mouse decidua","volume":"30","author":"Zhang","year":"2009","journal-title":"Placenta"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/978-1-61737-979-6_10","article-title":"In vivo depletion of FoxP3+ Tregs using the DEREG mouse model","volume":"707","author":"Lahl","year":"2011","journal-title":"Methods Mol. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.jim.2014.03.005","article-title":"Limitations of Foxp3(+) Treg depletion following viral infection in DEREG mice","volume":"406","author":"Christiaansen","year":"2014","journal-title":"J. Immunol. Methods"},{"key":"ref_22","first-page":"1465","article-title":"Progestogen for preventing miscarriage","volume":"10","author":"Haas","year":"2013","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2216","DOI":"10.1093\/humrep\/del150","article-title":"Evidence-based guidelines for the investigation and medical treatment of recurrent miscarriage","volume":"21","author":"Jauniaux","year":"2006","journal-title":"Hum. Reprod."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1093\/humupd\/dmt019","article-title":"Antithrombotic therapy for pregnancy loss","volume":"19","author":"Goddijn","year":"2013","journal-title":"Hum. Reprod. Update"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1111\/j.1600-0897.2012.01119.x","article-title":"The use of heparin for preventing miscarriage","volume":"67","author":"Check","year":"2012","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1016\/j.placenta.2015.07.133","article-title":"Sildenafil (Viagra(R)) blocks inflammatory injury in LPS-induced mouse abortion: A potential prophylactic treatment against acute pregnancy loss?","volume":"36","author":"Luna","year":"2015","journal-title":"Placenta"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1530\/jrf.0.0890447","article-title":"Control of fetal survival in CBA x DBA\/2 mice by lymphokine therapy","volume":"89","author":"Chaouat","year":"1990","journal-title":"J. Reprod. Fertil."},{"key":"ref_28","first-page":"215","article-title":"Controversies in reproductive immunology","volume":"11","author":"Clark","year":"1991","journal-title":"Crit. Rev. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1530\/jrf.0.0900395","article-title":"Lipopolysaccharide-induced fetal resorption in mice is associated with the intrauterine production of tumour necrosis factor-alpha","volume":"90","author":"Gendron","year":"1990","journal-title":"J. Reprod. Fertil."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"545","DOI":"10.4049\/jimmunol.160.2.545","article-title":"Cytokine-dependent abortion in CBA x DBA\/2 mice is mediated by the procoagulant fgl2 prothrombinase [correction of prothombinase]","volume":"160","author":"Clark","year":"1998","journal-title":"J. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0301-2115(98)00252-8","article-title":"Tumor necrosis factor during pregnancy and at the onset of labor and spontaneous abortion","volume":"83","author":"Daher","year":"1999","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1095\/biolreprod49.4.850","article-title":"Expression of cytokines in placentas of mice undergoing immunologically mediated spontaneous fetal resorptions","volume":"49","author":"Tangri","year":"1993","journal-title":"Biol. Reprod."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1038\/nm1452","article-title":"Decidual NK cells regulate key developmental processes at the human fetal-maternal interface","volume":"12","author":"Hanna","year":"2006","journal-title":"Nat. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1111\/j.1749-6632.1994.tb21746.x","article-title":"Human endometrial lymphocytes in normal pregnancy and pregnancy loss","volume":"734","author":"Bulmer","year":"1994","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1111\/j.1600-065X.2006.00447.x","article-title":"Uterine natural killer cells: A specialized differentiation regulated by ovarian hormones","volume":"214","author":"Croy","year":"2006","journal-title":"Immunol. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1111\/j.1600-0897.1995.tb00924.x","article-title":"Up-regulated expression of CD56+, CD56+\/CD16+, and CD19+ cells in peripheral blood lymphocytes in pregnant women with recurrent pregnancy losses","volume":"34","author":"Kwak","year":"1995","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1093\/humrep\/15.5.1163","article-title":"Peripheral natural killer cytotoxicity and CD56(pos)CD16(pos) cells increase during early pregnancy in women with a history of recurrent spontaneous abortion","volume":"15","author":"Emmer","year":"2000","journal-title":"Hum. Reprod."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"427","DOI":"10.33549\/physiolres.932923","article-title":"Alpha-actin down regulation and perforin loss in uterine natural killer cells from LPS-treated pregnant mice","volume":"64","author":"Zavan","year":"2015","journal-title":"Physiol. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1084\/jem.187.2.217","article-title":"Engraftment of bone marrow from severe combined immunodeficient (SCID) mice reverses the reproductive deficits in natural killer cell-deficient tg epsilon 26 mice","volume":"187","author":"Guimond","year":"1998","journal-title":"J. Exp. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.jri.2010.02.006","article-title":"Regulatory T cells are necessary for implantation and maintenance of early pregnancy but not late pregnancy in allogeneic mice","volume":"85","author":"Shima","year":"2010","journal-title":"J. Reprod. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1111\/j.1574-695X.2011.00805.x","article-title":"Depletion with PC61 mAb before Toxoplasma gondii infection eliminates mainly Tregs in BALB\/c mice, but activated cells in C57BL\/6J mice","volume":"62","author":"Tenorio","year":"2011","journal-title":"FEMS Immunol. Med. Microbiol."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/11\/7\/404\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:05:00Z","timestamp":1760187900000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/11\/7\/404"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,12]]},"references-count":41,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2019,7]]}},"alternative-id":["toxins11070404"],"URL":"https:\/\/doi.org\/10.3390\/toxins11070404","relation":{},"ISSN":["2072-6651"],"issn-type":[{"type":"electronic","value":"2072-6651"}],"subject":[],"published":{"date-parts":[[2019,7,12]]}}}