{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T03:48:11Z","timestamp":1793159291161,"version":"4.5.0"},"reference-count":134,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>\n                    Malaria, a disease caused by protozoa of the genus\n                    <jats:italic>Plasmodium<\/jats:italic>\n                    , remains a major challenge for global public health. The persistence of disease transmission to the mosquito vector depends on the differentiation of asexual blood-stage parasites into gametocytes, a process known as gametocytogenesis. Interrupting this stage of the parasite\u2019s life cycle represents a critical strategy for malaria control and eventual eradication. This review aims to consolidate recent advances in the understanding of the complex molecular mechanisms regulating gametocytogenesis in\n                    <jats:italic>Plasmodium<\/jats:italic>\n                    , with a particular focus on\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    . Sexual differentiation is modulated by various factors, including environmental stressors such as the depletion of lysophosphatidylcholine (LysoPC), and is orchestrated through a sophisticated regulatory network. At the transcriptional level, the AP2-G transcription factor functions as a master switch, whose expression is tightly regulated by epigenetic mechanisms, including histone H3K9 trimethylation (H3K9me3) as well as the activity of both heterochromatin protein 1 (HP1) and gametocyte development protein 1 (GDV1). Following commitment, post-transcriptional regulation plays a critical role in further differentiation, including transcript stabilization by RNA-binding proteins such as PfPuf1 and PfPuf2, along with epitranscriptomic modifications such as mRNA methylation (m\n                    <jats:sup>5<\/jats:sup>\n                    C and m\n                    <jats:sup>6<\/jats:sup>\n                    A), which modulate gene expression. A comprehensive understanding of these interconnected regulatory pathways is essential for the identification of novel therapeutic targets and the development of effective transmission-blocking vaccines.\n                  <\/jats:p>","DOI":"10.3389\/fmicb.2026.1736981","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T15:25:46Z","timestamp":1770218746000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Molecular mechanisms involved in Plasmodium gametocytogenesis"],"prefix":"10.3389","volume":"17","author":[{"given":"Aline Miranda","family":"Scovino","sequence":"first","affiliation":[{"name":"Immunoparasitology Laboratory, Oswaldo Cruz Institute (FIOCRUZ)","place":["Rio de Janeiro, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafaella St\u00e9fany","family":"Oliveira-da-Silva","sequence":"additional","affiliation":[{"name":"Immunoparasitology Laboratory, Oswaldo Cruz Institute (FIOCRUZ)","place":["Rio de Janeiro, Brazil"]},{"name":"Faculty of Medicine, Federal University of Rio de Janeiro (UFRJ)","place":["Rio de Janeiro, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce","family":"Almeida-da-Silva","sequence":"additional","affiliation":[{"name":"Immunoparasitology Laboratory, Oswaldo Cruz Institute (FIOCRUZ)","place":["Rio de Janeiro, Brazil"]},{"name":"Faculty of Medicine, Federal University of Rio de Janeiro (UFRJ)","place":["Rio de Janeiro, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolynne Dantas","family":"Mendes","sequence":"additional","affiliation":[{"name":"Immunoparasitology Laboratory, Oswaldo Cruz Institute (FIOCRUZ)","place":["Rio de Janeiro, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias Barbosa","family":"da Silva-Junior","sequence":"additional","affiliation":[{"name":"Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro (UFRJ)","place":["Rio de Janeiro, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debora","family":"Decote-Ricardo","sequence":"additional","affiliation":[{"name":"Veterinary Institute of the Federal Rural University of Rio de Janeiro (UFRRJ)","place":["Seropedica, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Freire-de-Lima","sequence":"additional","affiliation":[{"name":"Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro (UFRJ)","place":["Rio de Janeiro, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celio Geraldo","family":"Freire-de-Lima","sequence":"additional","affiliation":[{"name":"Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro (UFRJ)","place":["Rio de Janeiro, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo Renato Rivas","family":"Totino","sequence":"additional","affiliation":[{"name":"Laboratory for Malaria Research, Oswaldo Cruz Institute (FIOCRUZ)","place":["Rio de Janeiro, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Morrot","sequence":"additional","affiliation":[{"name":"Immunoparasitology Laboratory, Oswaldo Cruz Institute (FIOCRUZ)","place":["Rio de Janeiro, Brazil"]},{"name":"Faculty of Medicine, Federal University of Rio de Janeiro (UFRJ)","place":["Rio de Janeiro, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,4]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"e00295","DOI":"10.1016\/j.parepi.2023.e00295","article-title":"Biology and epidemiology of. 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