Ectopic pregnancy
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Maternal weight during pregnancy and risk of childhood acute lymphoblastic leukemia in offspring
In addition to biological factors, maternal exposures during pregnancy can contribute to leukemogenesis in offspring. We conducted a population-based cohort study in Sweden to investigate the association between risk of acute lymphoblastic leukemia (ALL) in offspring and maternal anthropometrics during pregnancy. A total of 2,961,435 live-born singletons during 1983–2018 were followed from birth to ALL diagnosis, end of age 18, or end of 2018. 1388 children were diagnosed with ALL (55.6% boys). We observed an increased risk of ALL among daughters of overweight/obese mothers in early pregnancy [Body mass index (BMI) ≥ 25 kg/m2; Standardized incidence ratio (SIR) = 1.4, 95% CI: 1.2–1.6] compared with the risk in daughters of mothers with normal BMI. This association was not found in their sons (SIR = 1.0, 95% CI: 0.9–1.1). Similar results were found for the association between ALL and maternal BMI before delivery. We did not find an association between low or high gestational weight gain (GWG) and risk of ALL (both SIRs = 1.0) in male/female offspring. These suggest that maternal overweight/obesity are important risk factors for childhood ALL in daughters, whereas GWG is not associated with risk of ALL. Further research on this mother-daughter association may shed light on a possible sex hormone/chromosome-related etiology of ALL.
Frequency and factors associated with the utilization (curative and preventive) of oral health care services among pregnant women in Kinshasa, Democratic Republic of Congo
The Democratic Republic of Congo (DRC) has one of the highest maternal and neonatal mortality rates in Africa. There is a growing body of evidence about the relationship between poor oral health and adverse pregnancy outcomes. However, there is a lack of information about oral health status during pregnancy in the DRC. This study aimed to identify the factors related to the utilization of oral health care services among pregnant women.
γδ T-cell autoresponses to ectopic membrane proteins: a new type of pattern recognition
T-cell receptor (TCR) γδ-expressing cells are conserved lymphocytes of innate immunity involved in first-line defense and immune surveillance. TCRγδ recognizes protein/nonprotein ligands without the help of the major histocompatibility complex (MHC), especially via direct binding to protein ligands, which is dependent primarily on the δ chain complementary determining region 3 (CDR3δ). However, the mechanism of protein‒antigen recognition by human γδ TCRs remains poorly defined. We hypothesize that γδ TCRs recognize self-proteins expressed ectopically on the cell membrane that are derived from intracellular components under stress. Here, we mapped 16 intercellular self-proteins among 21,000 proteins with a huProteinChip as putative ligands for Vδ1/Vδ2 TCRs, 13 for Vδ1 TCRs and 3 for Vδ2 TCRs. Functional tests confirmed that ectopic nucleolin (NCL) is a ligand for the Vδ1 TCR, whereas protein-glutamine γ-glutamyltransferase K (TGM1) is a ligand for the Vδ2 TCR. In the context of radiation exposure, the ectopic expression of intracellular proteins on the tumor cell surface is related to the increased antitumor cytotoxicity of γδ T cells both in vitro and in vivo. In conclusion, the recognition of intracellular proteins that are ectopically expressed on somatic cells by human γδ TCRs is a basic interaction mechanism that enables new types of immune pattern recognition and a novel γδ TCR-ligand-based strategy for tumor immunotherapy.
RAAS inhibitors in pregnancy, breastfeeding and women of childbearing potential: a review of national and international clinical practice guidelines
Globally prevalent conditions such as hypertension, heart failure, ischaemic heart disease (IHD) and chronic kidney disease (CKD) are frequently and effectively treated with blockers of the renin-angiotensin-aldosterone system (RAAS) as a first line treatment in the UK and worldwide. RAAS blockers are prohibited in pregnancy due to their adverse fetal effects. We reviewed clinical guidelines from the National Institute of Health and Care Excellence (NICE) on the management of cardiovascular and kidney disease with RAAS blockers in pregnancy, with other UK, European and American guidance as comparators. Whilst guidelines agree on the strict avoidance of RAAS blockers in pregnancy, nuanced considerations regarding prescription in women of childbearing potential, contraception, timing of RAAS blocker withdrawal and breastfeeding are not consistently addressed in clinical guidelines. We call for consistent wording and more explicit advice on RAAS blocker prescription in women of childbearing potential, in pregnancy and in the postpartum period in future iterations of clinical guidelines.
Macrophages: a double-edged sword in female reproduction and disorders
Reproduction consists of sequential inflammation-like events, primarily within the endometrium, from ovulation to embryo implantation, decidualization and delivery. During the reproductive cycle, the endometrium repeatedly undergoes cyclic periods of proliferation, differentiation, tissue breakdown and repair without scarring. Owing to their phagocytic activity, macrophages, key players in innate immunity, are thought to play crucial roles in the endometrium. Endometrial macrophages actively participate in various stages of reproductive tissue remodeling, particularly during decidualization and pregnancy establishment. Traditionally considered simple bystanders that clear debris to prevent autoimmune responses in tissue homeostasis, macrophages are now recognized as main actors with broad functional plasticity that allows them to fine tune the balance between pro- and anti-inflammatory responses during tissue inflammation, remodeling and repair. Homeostatic balance is determined by the sum of various mediators produced by two distinctly polarized macrophage subpopulations. The biased polarization of tissue-resident macrophages may contribute to the pathogenesis of various diseases, such as inflammation and cancer. Thus, understanding how macrophages contribute to endometrial homeostasis is crucial for deciphering the underlying mechanisms of various reproductive disorders. Nanomedicines using extracellular vesicles, nanoparticles and noncoding RNAs have recently been applied to modulate macrophage polarization and alleviate disease phenotypes. Despite these advances, the functions of endometrial macrophages under physiological and pathophysiological conditions remain poorly understood, which complicates the development of targeted therapies. Here we update the current understanding of the homeostatic function of macrophages and the putative contribution of endometrial macrophage dysfunction to reproductive disorders in women, along with innovative molecular therapeutics to resolve this issue.
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