Placental abnormalities have been sporadically implicated as a source of developmental heart defects. Yet it remains unknown how often the placenta is at the root of congenital heart defects (CHDs), and what the cellular mechanisms are that underpin this connection. Here, we selected three mouse mutant lines, Atp11a, Smg9 and Ssr2, that presented with placental and heart defects in a recent phenotyping screen, resulting in embryonic lethality. To dissect phenotype causality, we generated embryo- and trophoblast-specific conditional knockouts for each of these lines. This was facilitated by the establishment of a new transgenic mouse, Sox2-Flp, that enables the efficient generation of trophoblast-specific conditional knockouts. We demonstrate a strictly trophoblast-driven cause of the CHD and embryonic lethality in one of the three lines (Atp11a) and a significant contribution of the placenta to the embryonic phenotypes in another line (Smg9). Importantly, our data reveal defects in the maternal blood-facing syncytiotrophoblast layer as a shared pathology in placentally induced CHD models. This study highlights the placenta as a significant source of developmental heart disorders, insights that will transform our understanding of the vast number of unexplained congenital heart defects.

High survival rates in adolescent cancer patients have shifted the medical focus to the long-term outcomes of cancer treatments. Surgery, chemotherapy, and radiation increase the risk of infertility and infertility-related distress in adolescent cancer patients and survivors. The aims of this narrative review were to (1) describe the psychosocial impacts of cancer-related infertility in adolescents, (2) identify multilevel barriers to fertility preservation (FP) conversations and referrals, and (3) conclude with evidence-based clinical solutions for improving the oncofertility support available to Canadian adolescents. The results of this review revealed that FP decisions occur within the patient, parent, and health care provider (HCP) triad, and are influenced by factors such as parent attitudes, patient maturity, and HCP knowledge. Decision tools and HCP education can promote the occurrence of developmentally appropriate fertility discussions. At the systems level, cost and resource barriers prevent patients from receiving sufficient fertility information and referrals. Clinical models of care (MOCs) can define interdisciplinary roles and referral pathways to improve the integration of oncofertility services into adolescent cancer care. The continued integration of oncofertility care will ensure that all Canadian adolescents receive the exemplary medical and psychological support necessary to make empowered decisions about their own fertility.

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