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NSD2 is required for the normal development of humans and mice; however, its function during placentation remains unknown. Using genome editing techniques, we previously established two lines of <jats:italic>Nsd2<\/jats:italic>-mutant mice that showed growth retardation and neonatal lethality. Here, we further demonstrated that the loss-of-function mutation of NSD2 caused enlargement of the mouse placenta with morphological changes during late-gestation. <jats:italic>Nsd2<\/jats:italic>-mutant placentas were significantly heavier and showed thicker fetal layers with an expanded junctional zone and dilatated maternal blood sinuses in the labyrinth compared to their wild-type littermates. Abnormal placentation was accompanied by fetal growth defects, some with edema and one with a congenital cardiovascular anomaly, which may have partially affected neonatal survival. To our knowledge, this is the first study demonstrating the physiological and pathological functions of NSD2 during placentation.<\/jats:p>","DOI":"10.1371\/journal.pone.0328243","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T17:32:58Z","timestamp":1753119178000},"page":"e0328243","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Loss-of-function mutation of NSD2 is associated with abnormal placentation accompanied by fetal growth retardation in 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