{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T20:08:38Z","timestamp":1768421318986,"version":"3.49.0"},"reference-count":85,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T00:00:00Z","timestamp":1746403200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T00:00:00Z","timestamp":1746403200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["MND210518602191"],"award-info":[{"award-number":["MND210518602191"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004695","name":"University of KwaZulu-Natal","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004695","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Histochem Cell Biol"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The coronavirus disease 2019 (COVID-19) pandemic has passed; however, its long-term effects are yet to be determined. Pregnant women and their neonates faced a higher risk for complications during this pandemic as COVID-19 was reported to result in oxidative and inflammatory stress and the cytokine storm, which would impact pregnancy, namely the trophoblast invasion and placental development and functioning. Therefore, this study aims to determine the effect of COVID-19 on the placental functioning in South African pregnancies through the analysis of kisspeptin and placental morphology. Immunohistochemical analyses of placental samples were performed to detect the expression of kisspeptin. Histopathological analysis was conducted to identify vascular and inflammatory alterations. This study demonstrated that COVID-19 results in a significantly increased expression of placental kisspeptin in both the central (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.001) and peripheral (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001) regions as compared with the placentae from control pregnancies. Upon further analysis, the placentae from COVID-19 pregnancies also presented with severe inflammation and maternal and fetal vascular malperfusion compared with the control placentae. A significantly increased expression of placental kisspeptin was observed in COVID-19 positive pregnancies, implying impaired placental functioning. This was further supported by vascular and inflammatory alterations observed in COVID-19-positive placentae, which may suggest that trophoblast invasion was compromised. To date, there still exists small clusters of COVID-19 outbreaks, and our findings highlight the importance of the future surveillance of these mothers and neonates in COVID-19 pregnancies in South Africa, as neonates from other countries have presented with abnormalities.\n                  <\/jats:p>","DOI":"10.1007\/s00418-025-02381-6","type":"journal-article","created":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T10:13:30Z","timestamp":1746440010000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The effect of COVID-19 on placental functioning in South African pregnancies: investigation of kisspeptin expression and vascular and inflammatory alterations"],"prefix":"10.1007","volume":"163","author":[{"given":"C.","family":"Heeralall","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"U. H.","family":"Ibrahim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Jenneker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Singh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Matjila","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Lazarus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I.","family":"Mackraj","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,5,5]]},"reference":[{"issue":"3","key":"2381_CR1","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1002\/ijgo.13661","volume":"153","author":"M Abedzadeh-Kalahroudi","year":"2021","unstructured":"Abedzadeh-Kalahroudi M, Sehat M, Vahedpour Z, Talebian P (2021) Maternal and neonatal outcomes of pregnant patients with COVID-19: a prospective cohort study. Int J Gynaecol Obstet 153(3):449\u2013456","journal-title":"Int J Gynaecol Obstet"},{"issue":"4","key":"2381_CR2","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1159\/000509290","volume":"85","author":"H Akhtar","year":"2020","unstructured":"Akhtar H, Patel C, Abuelgasim E, Harky A (2020) COVID-19 (SARS-CoV-2) infection in pregnancy: a systematic review. Gynecol Obstet Invest 85(4):295\u2013306. https:\/\/doi.org\/10.1159\/000509290","journal-title":"Gynecol Obstet Invest"},{"issue":"2","key":"2381_CR3","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.ajog.2020.05.023","volume":"223","author":"GN Algarroba","year":"2020","unstructured":"Algarroba GN, Rekawek P, Vahanian SA, Khullar P, Palaia T, Peltier MR, Chavez MR, Vintzileos AM (2020) Visualization of severe acute respiratory syndrome coronavirus 2 invading the human placenta using electron microscopy. Am J Obstet Gynecol 223(2):275\u2013278","journal-title":"Am J Obstet Gynecol"},{"key":"2381_CR4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2024.104207","volume":"162","author":"\u015eL Altunta\u015f","year":"2024","unstructured":"Altunta\u015f \u015eL, G\u00fcne\u015f A, Kaplan AA, Ay\u015fit N, Keskin \u0130 (2024) Unravelling the impact of COVID-19 on pregnancy: in aspect of placental histopathology and umbilical cord macrophage immunoactivity with neonatal outcomes. J Reprod Immunol 162:104207. https:\/\/doi.org\/10.1016\/j.jri.2024.104207","journal-title":"J Reprod Immunol"},{"issue":"3","key":"2381_CR5","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1177\/1093526620925569","volume":"23","author":"RN Baergen","year":"2020","unstructured":"Baergen RN, Heller DS (2020) Placental pathology in covid-19 positive mothers: preliminary findings. Pediatr Dev Pathol 23(3):177\u2013180","journal-title":"Pediatr Dev Pathol"},{"issue":"4","key":"2381_CR6","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1080\/25787489.2021.1975608","volume":"22","author":"LK Barbera","year":"2021","unstructured":"Barbera LK, Kamis KF, Rowan SE, Davis AJ, Shehata S, Carlson JJ, Johnson SC, Erlandson KM (2021) HIV and COVID-19: review of clinical course and outcomes. HIV Res Clin Pract 22(4):102\u2013118","journal-title":"HIV Res Clin Pract"},{"issue":"21","key":"2381_CR7","doi-asserted-by":"crossref","first-page":"2198","DOI":"10.1001\/jama.2020.7233","volume":"323","author":"D Baud","year":"2020","unstructured":"Baud D, Greub G, Favre G, Gengler C, Jaton K, Dubruc E, Pomar L (2020) Second-trimester miscarriage in a pregnant woman with SARS-CoV-2 infection. JAMA 323(21):2198\u20132200","journal-title":"JAMA"},{"issue":"6","key":"2381_CR8","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1093\/humupd\/dmy030","volume":"24","author":"AL Boss","year":"2018","unstructured":"Boss AL, Chamley LW, James JL (2018) Placental formation in early pregnancy: how is the centre of the placenta made? Hum Reprod Update 24(6):750\u2013760. https:\/\/doi.org\/10.1093\/humupd\/dmy030","journal-title":"Hum Reprod Update"},{"issue":"1997","key":"2381_CR9","doi-asserted-by":"publisher","first-page":"20230191","DOI":"10.1098\/rspb.2023.0191","volume":"290","author":"GJ Burton","year":"2023","unstructured":"Burton GJ, Jauniaux E (2023) The human placenta: new perspectives on its formation and function during early pregnancy. Proc R Soc B Biol Sci 290(1997):20230191. https:\/\/doi.org\/10.1098\/rspb.2023.0191","journal-title":"Proc R Soc B Biol Sci"},{"issue":"1","key":"2381_CR10","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.placenta.2013.11.005","volume":"35","author":"G Burton","year":"2014","unstructured":"Burton G, Sebire N, Myatt L, Tannetta D, Wang Y-L, Sadovsky Y, Staff A, Redman C (2014) Optimising sample collection for placental research. Placenta 35(1):9\u201322","journal-title":"Placenta"},{"key":"2381_CR11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12958-018-0446-7","volume":"17","author":"Y Cao","year":"2019","unstructured":"Cao Y, Li Z, Jiang W, Ling Y, Kuang H (2019) Reproductive functions of kisspeptin\/KISS1R systems in the periphery. Reprod Biol Endocrinol 17:1\u20139","journal-title":"Reprod Biol Endocrinol"},{"issue":"1","key":"2381_CR12","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1530\/JOE-12-0091","volume":"214","author":"JE Cartwright","year":"2012","unstructured":"Cartwright JE, Williams PJ (2012) Altered placental expression of kisspeptin and its receptor in pre-eclampsia. J Endocrinol 214(1):79","journal-title":"J Endocrinol"},{"key":"2381_CR13","doi-asserted-by":"publisher","first-page":"S61","DOI":"10.1016\/j.jfma.2023.03.022","volume":"123","author":"H-J Chuang","year":"2024","unstructured":"Chuang H-J, Lin C-W, Hsiao M-Y, Wang T-G, Liang H-W (2024) Long COVID and rehabilitation. J Formos Med Assoc 123:S61\u2013S69. https:\/\/doi.org\/10.1016\/j.jfma.2023.03.022","journal-title":"J Formos Med Assoc"},{"issue":"24","key":"2381_CR14","doi-asserted-by":"crossref","first-page":"e3465","DOI":"10.21769\/BioProtoc.3465","volume":"9","author":"AR Crowe","year":"2019","unstructured":"Crowe AR, Yue W (2019) Semi-quantitative determination of protein expression using immunohistochemistry staining and analysis: an integrated protocol. Bio Protoc 9(24):e3465\u2013e3465","journal-title":"Bio Protoc"},{"key":"2381_CR15","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.humpath.2021.12.012","volume":"121","author":"C Dubucs","year":"2022","unstructured":"Dubucs C, Groussolles M, Ousselin J, Sartor A, Van Acker N, Vayssi\u00e8re C, Pasquier C, Reyre J, Batlle L, Courtade-Sa\u00efdi M (2022) Severe placental lesions due to maternal SARS-CoV-2 infection associated to intrauterine fetal death. Hum Pathol 121:46\u201355","journal-title":"Hum Pathol"},{"key":"2381_CR16","doi-asserted-by":"crossref","DOI":"10.1016\/j.ebiom.2020.102951","volume":"59","author":"F Facchetti","year":"2020","unstructured":"Facchetti F, Bugatti M, Drera E, Tripodo C, Sartori E, Cancila V, Papaccio M, Castellani R, Casola S, Boniotti MB (2020) SARS-CoV2 vertical transmission with adverse effects on the newborn revealed through integrated immunohistochemical, electron microscopy and molecular analyses of placenta. EBioMedicine 59:102951","journal-title":"EBioMedicine"},{"issue":"5","key":"2381_CR17","doi-asserted-by":"crossref","first-page":"pdb.prot4986","DOI":"10.1101\/pdb.prot4986","volume":"2008","author":"AH Fischer","year":"2008","unstructured":"Fischer AH, Jacobson KA, Rose J, Zeller R (2008) Hematoxylin and eosin staining of tissue and cell sections. Cold Spring Harb Protoc 2008(5):pdb.prot4986","journal-title":"Cold Spring Harb Protoc"},{"issue":"1","key":"2381_CR18","first-page":"1","volume":"16","author":"L Gao","year":"2021","unstructured":"Gao L, Ren J, Xu L, Ke X, Xiong L, Tian X, Fan C, Yan H, Yuan J (2021) Placental pathology of the third trimester pregnant women from COVID-19. Diagn Pathol 16(1):1\u201311","journal-title":"Diagn Pathol"},{"issue":"1","key":"2381_CR19","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1007\/s13224-022-01666-3","volume":"73","author":"R Garg","year":"2023","unstructured":"Garg R, Agarwal R, Yadav D, Singh S, Kumar H, Bhardwaj R (2023) Histopathological changes in placenta of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection and maternal and perinatal outcome in COVID-19. J Obstet Gynaecol India 73(1):44\u201350. https:\/\/doi.org\/10.1007\/s13224-022-01666-3","journal-title":"J Obstet Gynaecol India"},{"key":"2381_CR20","doi-asserted-by":"crossref","first-page":"1344086","DOI":"10.3389\/fimmu.2024.1344086","volume":"15","author":"R Gheorghita","year":"2024","unstructured":"Gheorghita R, Soldanescu I, Lobiuc A, Caliman Sturdza OA, Filip R, Constantinescu-Bercu A, Dimian M, Mangul S, Covasa M (2024) The knowns and unknowns of long COVID-19: from mechanisms to therapeutical approaches. Front Immunol 15:1344086","journal-title":"Front Immunol"},{"issue":"1","key":"2381_CR21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13000-021-01148-6","volume":"16","author":"G Giordano","year":"2021","unstructured":"Giordano G, Petrolini C, Corradini E, Campanini N, Esposito S, Perrone S (2021) COVID-19 in pregnancy: placental pathological patterns and effect on perinatal outcome in five cases. Diagn Pathol 16(1):1\u201313","journal-title":"Diagn Pathol"},{"issue":"1","key":"2381_CR22","doi-asserted-by":"crossref","first-page":"R41","DOI":"10.1152\/ajpregu.00258.2020","volume":"321","author":"VC Gomes","year":"2021","unstructured":"Gomes VC, Sones JL (2021) From inhibition of trophoblast cell invasion to proapoptosis: what are the potential roles of kisspeptins in preeclampsia? Am J Physiol Regul Integr Comp Physiol 321(1):R41\u2013R48","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"2381_CR23","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1134\/S0006297920080015","volume":"85","author":"O Gorbunova","year":"2020","unstructured":"Gorbunova O, Shirshev S (2020) Role of kisspeptin in regulation of reproductive and immune reactions. Biochem (Mosc) 85:839\u2013853","journal-title":"Biochem (Mosc)"},{"issue":"2","key":"2381_CR24","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1007\/s11906-021-01126-9","volume":"23","author":"R Govender","year":"2021","unstructured":"Govender R, Moodley J, Naicker T (2021) The COVID-19 pandemic: an appraisal of its impact on human immunodeficiency virus infection and pre-eclampsia. Curr Hypertens Rep 23(2):9. https:\/\/doi.org\/10.1007\/s11906-021-01126-9","journal-title":"Curr Hypertens Rep"},{"issue":"1","key":"2381_CR25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000515556","volume":"28","author":"MG Granja","year":"2021","unstructured":"Granja MG, da Rocha Oliveira AC, De Figueiredo CS, Gomes AP, Ferreira EC, Giestal-de-Araujo E, de Castro-Faria-Neto HC (2021) SARS-CoV-2 infection in pregnant women: neuroimmune-endocrine changes at the maternal-fetal interface. NeuroImmunoModulation 28(1):1\u201321","journal-title":"NeuroImmunoModulation"},{"issue":"11","key":"2381_CR26","doi-asserted-by":"crossref","first-page":"2092","DOI":"10.1038\/s41379-020-0639-4","volume":"33","author":"JL Hecht","year":"2020","unstructured":"Hecht JL, Quade B, Deshpande V, Mino-Kenudson M, Ting DT, Desai N, Dygulska B, Heyman T, Salafia C, Shen D (2020) SARS-CoV-2 can infect the placenta and is not associated with specific placental histopathology: a series of 19 placentas from COVID-19-positive mothers. Mod Pathol 33(11):2092\u20132103","journal-title":"Mod Pathol"},{"key":"2381_CR27","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.placenta.2023.05.009","volume":"138","author":"C Heeralall","year":"2023","unstructured":"Heeralall C, Ibrahim UH, Lazarus L, Gathiram P, Mackraj I (2023) The effects of COVID-19 on placental morphology. Placenta 138:88\u201396. https:\/\/doi.org\/10.1016\/j.placenta.2023.05.009","journal-title":"Placenta"},{"key":"2381_CR85","doi-asserted-by":"publisher","unstructured":"Heeralall C, Ibrahim UH, Jenneker M, Singh S, Lazarus L, Mackraj I (2025) Effect of COVID-19 infection during pregnancy on the plasma\/extracellular vesicles pro-inflammatory cytokine profile. Am J Reprod Immunol 93(4):e70071. https:\/\/doi.org\/10.1111\/aji.70071","DOI":"10.1111\/aji.70071"},{"issue":"9","key":"2381_CR28","doi-asserted-by":"crossref","first-page":"4947","DOI":"10.1172\/JCI139569","volume":"130","author":"H Hosier","year":"2020","unstructured":"Hosier H, Farhadian SF, Morotti RA, Deshmukh U, Lu-Culligan A, Campbell KH, Yasumoto Y, Vogels CB, Casanovas-Massana A, Vijayakumar P (2020) SARS\u2013CoV-2 infection of the placenta. J Clin Invest 130(9):4947","journal-title":"J Clin Invest"},{"issue":"2","key":"2381_CR29","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1002\/jmv.26386","volume":"93","author":"AL Hsu","year":"2021","unstructured":"Hsu AL, Guan M, Johannesen E, Stephens AJ, Khaleel N, Kagan N, Tuhlei BC, Wan XF (2021) Placental SARS-CoV-2 in a pregnant woman with mild COVID-19 disease. J Med Virol 93(2):1038\u20131044","journal-title":"J Med Virol"},{"key":"2381_CR30","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/j.ejogrb.2019.07.016","volume":"240","author":"K-L Hu","year":"2019","unstructured":"Hu K-L, Zhao H, Yu Y, Li R (2019) Kisspeptin as a potential biomarker throughout pregnancy. Eur J Obstet Gynecol Reprod Biol 240:261\u2013266. https:\/\/doi.org\/10.1016\/j.ejogrb.2019.07.016","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"2381_CR31","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.jri.2013.04.003","volume":"101\u2013102","author":"B Huppertz","year":"2014","unstructured":"Huppertz B, Weiss G, Moser G (2014) Trophoblast invasion and oxygenation of the placenta: measurements versus presumptions. J Reprod Immunol 101\u2013102:74\u201379. https:\/\/doi.org\/10.1016\/j.jri.2013.04.003","journal-title":"J Reprod Immunol"},{"issue":"3","key":"2381_CR32","doi-asserted-by":"crossref","first-page":"e225345","DOI":"10.1001\/jamanetworkopen.2022.5345","volume":"5","author":"A Huynh","year":"2022","unstructured":"Huynh A, Sehn JK, Goldfarb IT, Watkins J, Torous V, Heerema-McKenney A, Roberts DJ (2022) SARS-CoV-2 placentitis and intraparenchymal thrombohematomas among COVID-19 infections in pregnancy. JAMA Netw Open 5(3):e225345\u2013e225345","journal-title":"JAMA Netw Open"},{"key":"2381_CR33","first-page":"1935","volume":"12","author":"G Ikhtiyarova","year":"2021","unstructured":"Ikhtiyarova G, Dustova N, Khasanova M, Suleymanova G, Davlatov S (2021) Pathomorphological changes of the placenta in pregnant women infected with coronavirus COVID-19. Int J Pharm Res 12:1935\u20131942","journal-title":"Int J Pharm Res"},{"issue":"7","key":"2381_CR34","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1007\/BF03345620","volume":"31","author":"T Iwasa","year":"2008","unstructured":"Iwasa T, Matsuzaki T, Murakami M, Shimizu F, Kuwahara A, Yasui T, Irahara M (2008) Decreased expression of kisspeptin mediates acute immune\/inflammatory stress-induced suppression of gonadotropin secretion in female rat. J Endocrinol Invest 31(7):656\u2013659. https:\/\/doi.org\/10.1007\/BF03345620","journal-title":"J Endocrinol Invest"},{"key":"2381_CR35","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.ejogrb.2021.01.049","volume":"259","author":"N Jaiswal","year":"2021","unstructured":"Jaiswal N, Puri M, Agarwal K, Singh S, Yadav R, Tiwary N, Tayal P, Vats B (2021) COVID-19 as an independent risk factor for subclinical placental dysfunction. Eur J Obstet Gynecol Reprod Biol 259:7\u201311","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"2381_CR36","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.ajog.2021.08.054","volume":"226","author":"DJ Jamieson","year":"2021","unstructured":"Jamieson DJ, Rasmussen SA (2021) An update on COVID-19 and pregnancy. Am J Obstet Gynecol 226:177","journal-title":"Am J Obstet Gynecol"},{"issue":"11","key":"2381_CR37","doi-asserted-by":"crossref","first-page":"5709","DOI":"10.3390\/ijerph18115709","volume":"18","author":"W-K Jang","year":"2021","unstructured":"Jang W-K, Lee S-Y, Park S, Ryoo NH, Hwang I, Park JM, Bae J-G (2021) Pregnancy outcome, antibodies, and placental pathology in SARS-CoV-2 infection during early pregnancy. Int J Environ Res Public Health 18(11):5709","journal-title":"Int J Environ Res Public Health"},{"issue":"3","key":"2381_CR38","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1002\/ar.22641","volume":"296","author":"EC Jensen","year":"2013","unstructured":"Jensen EC (2013) Quantitative analysis of histological staining and fluorescence using ImageJ. Anat Rec 296(3):378\u2013381","journal-title":"Anat Rec"},{"issue":"2","key":"2381_CR39","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/s00404-019-05408-1","volume":"301","author":"R Kapustin","year":"2020","unstructured":"Kapustin R, Drobintseva A, Alekseenkova E, Onopriychuk A, Arzhanova O, Polyakova V, Kvetnoy I (2020) Placental protein expression of kisspeptin-1 (KISS1) and the kisspeptin-1 receptor (KISS1R) in pregnancy complicated by diabetes mellitus or preeclampsia. Arch Gynecol Obstet 301(2):437\u2013445","journal-title":"Arch Gynecol Obstet"},{"key":"2381_CR40","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1111\/jog.15302","volume":"48","author":"M Kato","year":"2022","unstructured":"Kato M, Yamaguchi K, Maegawa Y, Komine-Aizawa S, Kondo E, Ikeda T (2022) Intrauterine fetal death during COVID-19 pregnancy: typical fetal heart rate changes, coagulopathy, and placentitis. J Obstet Gynaecol Res 48:1978","journal-title":"J Obstet Gynaecol Res"},{"issue":"1","key":"2381_CR41","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1080\/03630242.2021.2007199","volume":"62","author":"K Khoiwal","year":"2022","unstructured":"Khoiwal K, Agarwal A, Gaurav A, Kumari R, Mittal A, Sabnani S, Mundhra R, Chawla L, Bahadur A, Chaturvedi J (2022) Obstetric and perinatal outcomes in pregnant women with COVID-19: an interim analysis. Women Health 62(1):12\u201320","journal-title":"Women Health"},{"issue":"2","key":"2381_CR42","doi-asserted-by":"crossref","first-page":"43","DOI":"10.17816\/JOWD68243-50","volume":"68","author":"TS Kleimenova","year":"2019","unstructured":"Kleimenova TS, Drobintseva AO, Polyakova VO, Tsypurdeyeva AA (2019) Expression of kisspeptin and matrix metalloproteinases in human endometrial culture: a study of invasive and migratory properties. J. Obstet. Women\u2019s Dis 68(2):43\u201350","journal-title":"J. Obstet. Women\u2019s Dis"},{"key":"2381_CR43","doi-asserted-by":"crossref","first-page":"793561","DOI":"10.3389\/fped.2021.793561","volume":"9","author":"H-Y Liu","year":"2021","unstructured":"Liu H-Y, Guo J, Zeng C, Cao Y, Ran R, Wu T, Yang G, Zhao D, Yang P, Yu X (2021) Transient early fine motor abnormalities in infants born to COVID-19 mothers are associated with placental hypoxia and ischemia. Front Pediatr 9:793561","journal-title":"Front Pediatr"},{"issue":"2","key":"2381_CR44","doi-asserted-by":"crossref","first-page":"93","DOI":"10.5005\/jp-journals-10006-2397","volume":"16","author":"MM Londhe","year":"2024","unstructured":"Londhe MM, Patil TV, Akhare S (2024) Histopathological evaluation of placentas from COVID-19-positive mothers: a study of 100 placentas. JSAFOG 16(2):93\u201397","journal-title":"JSAFOG"},{"issue":"1","key":"2381_CR45","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1080\/22221751.2020.1775132","volume":"9","author":"SA Lone","year":"2020","unstructured":"Lone SA, Ahmad A (2020) COVID-19 pandemic\u2014An African perspective. Emerg Microbes Infect 9(1):1300\u20131308","journal-title":"Emerg Microbes Infect"},{"key":"2381_CR46","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.placenta.2021.12.002","volume":"117","author":"Q Mao","year":"2022","unstructured":"Mao Q, Chu S, Shapiro S, Young L, Russo M, De Paepe ME (2022) Placental SARS-CoV-2 distribution correlates with level of tissue oxygenation in COVID-19-associated necrotizing histiocytic intervillositis\/perivillous fibrin deposition. Placenta 117:187\u2013193","journal-title":"Placenta"},{"issue":"1","key":"2381_CR47","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.preghy.2015.11.001","volume":"6","author":"M Matjila","year":"2016","unstructured":"Matjila M, Millar R, van der Spuy Z, Katz A (2016) Elevated placental expression at the maternal\u2013fetal interface but diminished maternal circulatory kisspeptin in preeclamptic pregnancies. Pregnancy Hypertens 6(1):79\u201387. https:\/\/doi.org\/10.1016\/j.preghy.2015.11.001","journal-title":"Pregnancy Hypertens"},{"key":"2381_CR48","unstructured":"Matjila MJ (2015) The role of kisspeptin and its cognate receptor GPR54 in normal and abnormal placentation. In: Dissertation, University of Cape Town"},{"issue":"1","key":"2381_CR49","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1159\/000511324","volume":"88","author":"T Menter","year":"2021","unstructured":"Menter T, Mertz KD, Jiang S, Chen H, Monod C, Tzankov A, Waldvogel S, Schulzke SM, H\u00f6sli I, Bruder E (2021) Placental pathology findings during and after SARS-CoV-2 infection: features of villitis and malperfusion. Pathobiology 88(1):69\u201377","journal-title":"Pathobiology"},{"issue":"8","key":"2381_CR50","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1111\/1471-0528.17458","volume":"130","author":"C Milot","year":"2023","unstructured":"Milot C, Koch A, Averous G, Mayeur S, Deruelle P (2023) Development of placental lesions after recovery from COVID-19 during pregnancy: case\u2013control study. BJOG 130(8):949\u2013958. https:\/\/doi.org\/10.1111\/1471-0528.17458","journal-title":"BJOG"},{"issue":"5","key":"2381_CR51","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1002\/uog.22189","volume":"56","author":"J Mongula","year":"2020","unstructured":"Mongula J, Frenken M, Van Lijnschoten G, Arents N, de Wit-Zuurendonk L, Schimmel-de Kok A, van Runnard HP, Porath M, Goossens S (2020) COVID-19 during pregnancy: non-reassuring fetal heart rate, placental pathology and coagulopathy. Ultrasound Obstet Gynecol 56(5):773\u2013776","journal-title":"Ultrasound Obstet Gynecol"},{"key":"2381_CR52","volume":"46","author":"JJ Mulvey","year":"2020","unstructured":"Mulvey JJ, Magro CM, Ma LX, Nuovo GJ, Baergen RN (2020) Analysis of complement deposition and viral RNA in placentas of COVID-19 patients. Ann Diagn Pathol 46:151530","journal-title":"Ann Diagn Pathol"},{"key":"2381_CR53","doi-asserted-by":"publisher","first-page":"05050","DOI":"10.7189\/jogh.12.05050","volume":"12","author":"MC Nunes","year":"2022","unstructured":"Nunes MC, Jones S, Strehlau R, Baba V, Ditse Z, da Silva K, Bothma L, Serafin N, Baillie VL, Kwatra G, Burke M, Wise A, Adam M, Mlandu P, Melamu M, Phelp J, Fraser W, Wright C, Zell E, Adam Y, Madhi SA (2022) Antepartum SARS-CoV-2 infection and adverse birth outcomes in South African women. J Glob Health 12:05050. https:\/\/doi.org\/10.7189\/jogh.12.05050","journal-title":"J Glob Health"},{"issue":"4","key":"2381_CR54","doi-asserted-by":"crossref","first-page":"382. e381","DOI":"10.1016\/j.ajog.2020.10.020","volume":"224","author":"ET Patberg","year":"2021","unstructured":"Patberg ET, Adams T, Rekawek P, Vahanian SA, Akerman M, Hernandez A, Rapkiewicz AV, Ragolia L, Sicuranza G, Chavez MR (2021) Coronavirus disease 2019 infection and placental histopathology in women delivering at term. Am J Obstet Gynecol 224(4):382. e381-382. e318","journal-title":"Am J Obstet Gynecol"},{"issue":"12","key":"2381_CR55","doi-asserted-by":"crossref","first-page":"2441","DOI":"10.1007\/s10096-020-03964-y","volume":"39","author":"B Pulinx","year":"2020","unstructured":"Pulinx B, Kieffer D, Michiels I, Petermans S, Strybol D, Delvaux S, Baldewijns M, Raymaekers M, Cartuyvels R, Maurissen W (2020) Vertical transmission of SARS-CoV-2 infection and preterm birth. Eur J Clin Microbiol Infect Dis 39(12):2441\u20132445","journal-title":"Eur J Clin Microbiol Infect Dis"},{"issue":"11","key":"2381_CR56","volume":"7","author":"C Qiao","year":"2012","unstructured":"Qiao C, Wang C, Zhao J, Liu C, Shang T (2012) Elevated expression of KiSS-1 in placenta of Chinese women with early-onset preeclampsia. PLoS\u00a0One 7(11):e48937","journal-title":"PLoS\u00a0One"},{"key":"2381_CR57","first-page":"100153","volume":"15","author":"S Ramphal","year":"2022","unstructured":"Ramphal S, Govender N, Singh S, Khaliq O, Naicker T (2022) Histopathological features in advanced abdominal pregnancies co-infected with SARS-CoV-2 and HIV-1 infections: a case evaluation. Eur J Obstet Gynecol Reprod Biol X 15:100153","journal-title":"Eur J Obstet Gynecol Reprod Biol X"},{"key":"2381_CR58","volume":"27","author":"R Richtmann","year":"2020","unstructured":"Richtmann R, Torloni MR, Otani ARO, Levi JE, Tobara MC, de Almeida SC, Dias L, Miglioli-Galv\u00e3o L, Silva PM, Kondo MM (2020) Fetal deaths in pregnancies with SARS-CoV-2 infection in Brazil: a case series. Case Rep Womens Health 27:e00243","journal-title":"Case Rep Womens Health"},{"issue":"1","key":"2381_CR59","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1097\/pgp.0000000000000948","volume":"43","author":"EE Ryan","year":"2024","unstructured":"Ryan EE, Brar N, Allard G, Wang A, Winn VD, Folkins A, Yang EJ, Tan S, Hazard FK, Howitt BE (2024) Clinical features of SARS-CoV-2 infection during pregnancy and associated placental pathologies. Int J Gynecol Pathol 43(1):15\u201324. https:\/\/doi.org\/10.1097\/pgp.0000000000000948","journal-title":"Int J Gynecol Pathol"},{"issue":"5","key":"2381_CR60","doi-asserted-by":"crossref","first-page":"517","DOI":"10.5858\/arpa.2020-0771-SA","volume":"145","author":"DA Schwartz","year":"2021","unstructured":"Schwartz DA, Baldewijns M, Benachi A, Bugatti M, Collins RR, De Luca D, Facchetti F, Linn RL, Marcelis L, Morotti D (2021) Chronic histiocytic intervillositis with trophoblast necrosis is a risk factor associated with placental infection from coronavirus disease 2019 (COVID-19) and intrauterine maternal-fetal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in live-born and stillborn infants. Arch Pathol Lab Med 145(5):517\u2013528","journal-title":"Arch Pathol Lab Med"},{"issue":"6","key":"2381_CR61","doi-asserted-by":"crossref","first-page":"660","DOI":"10.5858\/arpa.2022-0029-SA","volume":"146","author":"DA Schwartz","year":"2022","unstructured":"Schwartz DA, Avvad-Portari E, Bab\u00e1l P, Baldewijns M, Blomberg M, Bouachba A, Camacho J, Collardeau-Frachon S, Colson A, Dehaene I (2022) Placental tissue destruction and insufficiency from COVID-19 causes stillbirth and neonatal death from hypoxic-ischemic injury: a study of 68 cases with SARS-CoV-2 placentitis from 12 countries. Arch Pathol Lab Med 146(6):660\u2013676","journal-title":"Arch Pathol Lab Med"},{"issue":"5","key":"2381_CR62","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.1002\/jmv.26857","volume":"93","author":"CM Seymen","year":"2021","unstructured":"Seymen CM (2021) Being pregnant in the COVID-19 pandemic: effects on the placenta in all aspects. J Med Virol 93(5):2769\u20132773","journal-title":"J Med Virol"},{"issue":"1","key":"2381_CR63","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1093\/ajcp\/aqaa089","volume":"154","author":"ED Shanes","year":"2020","unstructured":"Shanes ED, Mithal LB, Otero S, Azad HA, Miller ES, Goldstein JA (2020) Placental pathology in COVID-19. Am J Clin Pathol 154(1):23\u201332","journal-title":"Am J Clin Pathol"},{"issue":"3","key":"2381_CR64","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s10517-021-05236-x","volume":"171","author":"A Shchegolev","year":"2021","unstructured":"Shchegolev A, Kulikova G, Lyapin V, Shmakov R, Sukhikh G (2021) The number of syncytial knots and VEGF expression in placental villi in parturient woman with COVID-19 depends on the disease severity. Bull Exp Biol Med 171(3):399\u2013403","journal-title":"Bull Exp Biol Med"},{"issue":"1\u20132","key":"2381_CR65","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1080\/19336918.2015.1120397","volume":"10","author":"JF Silva","year":"2016","unstructured":"Silva JF, Serakides R (2016) Intrauterine trophoblast migration: a comparative view of humans and rodents. Cell Adh Migr 10(1\u20132):88\u2013110","journal-title":"Cell Adh Migr"},{"issue":"9","key":"2381_CR66","doi-asserted-by":"crossref","first-page":"e265","DOI":"10.1097\/INF.0000000000002815","volume":"39","author":"J Sisman","year":"2020","unstructured":"Sisman J, Jaleel MA, Moreno W, Rajaram V, Collins RR, Savani RC, Rakheja D, Evans AS (2020) Intrauterine transmission of SARS-COV-2 infection in a preterm infant. Pediatr Infect Dis J 39(9):e265\u2013e267","journal-title":"Pediatr Infect Dis J"},{"issue":"6","key":"2381_CR67","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1111\/his.14215","volume":"77","author":"MC Smithgall","year":"2020","unstructured":"Smithgall MC, Liu-Jarin X, Hamele-Bena D, Cimic A, Mourad M, Debelenko L, Chen X (2020) Third-trimester placentas of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive women: histomorphology, including viral immunohistochemistry and in-situ hybridization. Histopathology 77(6):994\u2013999","journal-title":"Histopathology"},{"key":"2381_CR68","volume-title":"Bancroft\u2019s Theory and Practice of Histological Techniques","author":"KS Suvarna","year":"2018","unstructured":"Suvarna KS, Layton C, Bancroft JD (2018) Bancroft\u2019s Theory and Practice of Histological Techniques. Elsevier health sciences"},{"issue":"1","key":"2381_CR69","first-page":"39","volume":"3","author":"A Suvik","year":"2012","unstructured":"Suvik A, Effendy A (2012) The use of modified Masson\u2019s trichrome staining in collagen evaluation in wound healing study. Mal J Vet Res 3(1):39\u201347","journal-title":"Mal J Vet Res"},{"issue":"8","key":"2381_CR70","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1177\/1933719108322442","volume":"15","author":"M Torricelli","year":"2008","unstructured":"Torricelli M, Galleri L, Voltolini C, Biliotti G, Florio P, De Bonis M, Petraglia F (2008) Changes of placental kiss-1 mRNA expression and maternal\/cord kisspeptin levels at preterm delivery. Reprod Sci 15(8):779\u2013784","journal-title":"Reprod Sci"},{"issue":"2","key":"2381_CR71","first-page":"25","volume":"18","author":"S Tripathy","year":"2024","unstructured":"Tripathy S, Sreelakshmi S, Das A (2024) Histopathological changes and clinical outcomes in placentas of COVID-19 positive mothers: a cohort study. J Clin Diagn Res 18(2):25","journal-title":"J Clin Diagn Res"},{"issue":"3","key":"2381_CR72","doi-asserted-by":"crossref","first-page":"243","DOI":"10.5005\/jp-journals-10006-2426","volume":"16","author":"G Umamaheswari","year":"2024","unstructured":"Umamaheswari G, Natarajan L, Subbarao TM, Chaitra V, Lathamaheswari S, Ramya T (2024) Placental pathology in correlation with inflammatory markers and perinatal outcomes in maternal COVID: a prospective study. JSAFOG 16(3):243\u2013251","journal-title":"JSAFOG"},{"key":"2381_CR73","unstructured":"Vannevel V, Hlongwane T, Wright C, Feucht U, Soma-Pillay P, Adam S, Mulol H, Fosu-Amoah D, Van Deventer H, Venter M Placental histology and umbilical artery Doppler in pregnant women with severe COVID-19. In: BJOG, 2021. WILEY 111 RIVER ST, HOBOKEN 07030\u20135774, NJ USA, pp 203\u2013203"},{"issue":"3","key":"2381_CR74","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1111\/tmi.13383","volume":"25","author":"TP Velavan","year":"2020","unstructured":"Velavan TP, Meyer CG (2020) The COVID-19 epidemic. Trop Med Int Health 25(3):278","journal-title":"Trop Med Int Health"},{"issue":"1","key":"2381_CR75","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-020-17436-6","volume":"11","author":"AJ Vivanti","year":"2020","unstructured":"Vivanti AJ, Vauloup-Fellous C, Prevot S, Zupan V, Suffee C, Do Cao J, Benachi A, De Luca D (2020) Transplacental transmission of SARS-CoV-2 infection. Nat Commun 11(1):1\u20137","journal-title":"Nat Commun"},{"key":"2381_CR76","first-page":"65","volume":"8","author":"D Vodneva","year":"2014","unstructured":"Vodneva D, Dubova E, Pavlov K, Shmakov R, Shchegolev A (2014) Role of kisspeptins in the development of early-and late-onset preeclampsia. Obstet Gyncol 8:65\u201370","journal-title":"Obstet Gyncol"},{"issue":"4","key":"2381_CR77","doi-asserted-by":"publisher","first-page":"202","DOI":"10.3349\/ymj.2023.0309","volume":"65","author":"MP Wardhana","year":"2024","unstructured":"Wardhana MP, Kuntaman K, Utomo B, Aryananda RA, Rifdah SN, Wafa IA, Shahnaz AA, Ningrum D, Cininta NI, Ariani G, Van Lith JM, Dachlan EG (2024) Evidence of placental villous inflammation and apoptosis in third-trimester symptomatic SARS-CoV-2 maternal infection. Yonsei Med J 65(4):202\u2013209. https:\/\/doi.org\/10.3349\/ymj.2023.0309","journal-title":"Yonsei Med J"},{"issue":"1","key":"2381_CR78","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1152\/physrev.00024.2020","volume":"101","author":"EA Wastnedge","year":"2021","unstructured":"Wastnedge EA, Reynolds RM, van Boeckel SR, Stock SJ, Denison FC, Maybin JA, Critchley HO (2021) Pregnancy and COVID-19. Physiol Rev 101(1):303\u2013318","journal-title":"Physiol Rev"},{"issue":"11","key":"2381_CR79","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.5858\/arpa.2021-0246-SA","volume":"145","author":"JC Watkins","year":"2021","unstructured":"Watkins JC, Torous VF, Roberts DJ (2021) Defining severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Placentitis: a report of 7 cases with confirmatory in situ hybridization, distinct histomorphologic features, and evidence of complement deposition. Arch Pathol Lab Med 145(11):1341\u20131349","journal-title":"Arch Pathol Lab Med"},{"key":"2381_CR80","doi-asserted-by":"crossref","first-page":"e62","DOI":"10.1590\/s1678-9946202062062","volume":"62","author":"Y Wenling","year":"2020","unstructured":"Wenling Y, Junchao Q, Xiao Z, Ouyang S (2020) Pregnancy and COVID-19: management and challenges. Rev Inst Med Trop Sao Paulo 62:e62","journal-title":"Rev Inst Med Trop Sao Paulo"},{"key":"2381_CR81","unstructured":"WHO WHO (2024) WHO COVID-19 dashboard."},{"issue":"44","key":"2381_CR82","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.15585\/mmwr.mm6944e3","volume":"69","author":"LD Zambrano","year":"2020","unstructured":"Zambrano LD, Ellington S, Strid P, Galang RR, Oduyebo T, Tong VT, Woodworth KR, Nahabedian JF III, Azziz-Baumgartner E, Gilboa SM (2020) Update: characteristics of symptomatic women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status\u2014United States, January 22\u2013October 3, 2020. Morb Mortal Wkly Rep 69(44):1641","journal-title":"Morb Mortal Wkly Rep"},{"issue":"2","key":"2381_CR83","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/S1642-431X(12)60048-5","volume":"11","author":"H Zhang","year":"2011","unstructured":"Zhang H, Long Q, Ling L, Gao A, Li H, Lin Q (2011) Elevated expression of KiSS-1 in placenta of preeclampsia and its effect on trophoblast. Reprod Biol 11(2):99\u2013115. https:\/\/doi.org\/10.1016\/S1642-431X(12)60048-5","journal-title":"Reprod Biol"},{"key":"2381_CR84","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1002\/jum.16444","volume":"43","author":"F Zhu","year":"2024","unstructured":"Zhu F, Zhao Y, Wu J, Wang M, Zhu Z, Zhang L (2024) Post-COVID-19 fetal cardiac morphology and systolic evaluation in infected pregnant women by fetal heart quantification technology. J Ultrasound Med 43:1199","journal-title":"J Ultrasound Med"}],"container-title":["Histochemistry and Cell Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00418-025-02381-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00418-025-02381-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00418-025-02381-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T11:26:31Z","timestamp":1768389991000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00418-025-02381-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,5]]},"references-count":85,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["2381"],"URL":"https:\/\/doi.org\/10.1007\/s00418-025-02381-6","relation":{},"ISSN":["0948-6143","1432-119X"],"issn-type":[{"value":"0948-6143","type":"print"},{"value":"1432-119X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,5]]},"assertion":[{"value":"10 April 2025","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 May 2025","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that there is no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Regulatory ethical and institutional approval was obtained from the Biomedical Research Ethics Committee of the University of KwaZulu-Natal (no. BREC\/00004591\/2022), South Africa. Patients were recruited on the basis of the inclusion and exclusion criteria. Once they were identified, the purpose and requirements of this study were explained to them. Upon agreeing to participate, all participants signed a consent form.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}],"article-number":"49"}}