bims-reprim 2021-12-05 papers

Nat Commun. 2021 Dec 03. 12(1): 7049

'Fetal side' of the placenta: anatomical mis-annotation of carbon particle 'transfer' across the human placenta.

Beth Holder, John D Aplin, Nardhy Gomez-Lopez, Alexander E P Heazell, Joanna L James, Carolyn J P Jones, Helen Jones, Rohan M Lewis, Gil Mor, Claire T Roberts, Sarah A Robertson, Ana C Zenclussen.

DOI: https://doi.org/10.1038/s41467-021-26437-y

EBioMedicine. 2021 Nov 26. pii: S2352-3964(21)00515-6. [Epub ahead of print]74 103721

Grandmaternal cells in cord blood.

Karlin R Karlmark, Marina El Haddad, Xavier-Côme Donato, Gabriel V Martin, Florence Bretelle, Nathalie Lesavre, Jean-François Cocallemen, Marielle Martin, Christophe Picard, Tiffany Albentosa, Jean Roudier, Raoul Desbriere, Nathalie C Lambert.

BACKGROUND: During pregnancy a feto-maternal exchange of cells through the placenta conducts to maternal microchimerism (Mc) in the child and fetal Mc in the mother. Because of this bidirectional traffic of cells, pregnant women have also acquired maternal cells in utero from their mother and could transfer grandmaternal (GdM) cells to their child through the maternal bloodstream during pregnancy. Thus, cord blood (CB) samples could theoretically carry GdMMc. Nevertheless this has never been demonstrated.METHODS: Using Human Leukocyte Antigen (HLA)-specific quantitative PCR assays on three-generation families, we were able to test 28 CB samples from healthy primigravid women for GdMMc in whole blood (WB) and isolated cells (PBMC, T, B, granulocytes, stem cells).
FINDINGS: Five CB samples (18%) had GdMMc which could not be confounded with maternal source, with quantities 100 fold lower than maternal Mc in WB and PBMC. Risk of aneuploidies and/or related invasive prenatal procedures significantly correlated with the presence of GdMMc in CB (p=0.024). Significantly decreased HLA compatibility was observed in three-generation families from CB samples carrying GdMMc (p=0.019).
INTERPRETATION: Transgenerational transfer of cells could have implications in immunology and evolution. Further analyses will be necessary to evaluate whether GdMMc in CB is a passive or immunologically active transfer and whether invasive prenatal procedures could trigger GdMMc.
FUNDING: Provence-Alpes-Côte d'Azur APEX grant # 2012_06549E, 2012_11786F and 2014_03978) and the Foundation for Medical Research (FRM Grant #ING20140129045).

Keywords: Cord blood; HLA compatibility; grandmaternal microchimerism; three generations

DOI: https://doi.org/10.1016/j.ebiom.2021.103721

Nat Genet. 2021 Dec 02.

Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro.

The endometrium, the mucosal lining of the uterus, undergoes dynamic changes throughout the menstrual cycle in response to ovarian hormones. We have generated dense single-cell and spatial reference maps of the human uterus and three-dimensional endometrial organoid cultures. We dissect the signaling pathways that determine cell fate of the epithelial lineages in the lumenal and glandular microenvironments. Our benchmark of the endometrial organoids reveals the pathways and cell states regulating differentiation of the secretory and ciliated lineages both in vivo and in vitro. In vitro downregulation of WNT or NOTCH pathways increases the differentiation efficiency along the secretory and ciliated lineages, respectively. We utilize our cellular maps to deconvolute bulk data from endometrial cancers and endometriotic lesions, illuminating the cell types dominating in each of these disorders. These mechanistic insights provide a platform for future development of treatments for common conditions including endometriosis and endometrial carcinoma.

DOI: https://doi.org/10.1038/s41588-021-00972-2

Lancet Oncol. 2021 Dec;pii: S1470-2045(21)00525-8. [Epub ahead of print]22(12): e550-e561

Immunotherapy for cancer treatment during pregnancy.

Jessica S W Borgers, Joosje H Heimovaara, Elyce Cardonick, Daan Dierickx, Matteo Lambertini, John B A G Haanen, Frédéric Amant.

Immunotherapy has greatly improved outcomes for subgroups of patients with cancer. As indications keep expanding, there is an unmet need to gain a better understanding of the effect of these therapies on pregnancy and fertility. During pregnancy, substantial adaptations occur in the maternal immune system to maintain protection against pathogens while avoiding detrimental reactions to the semi-allogeneic fetus. The pathways involved in the establishment of this fetomaternal tolerance can be hijacked by cancers. Immunotherapies that target these inhibitory pathways, or that directly interact with the regulatory immune cells involved in tolerance mechanisms, might therefore result in complications during pregnancy. Similarly, by activating the patient's immune system with immunotherapy, a broad range of immune-related adverse events can occur that could negatively affect the fetus or impede a future desired pregnancy. This Review summarises preclinical and clinical data related to the use of immunotherapy during pregnancy, including all approved immune checkpoint inhibitors, recombinant cytokines, cell therapies, vaccines, and immunomodulatory drugs.

DOI: https://doi.org/10.1016/S1470-2045(21)00525-8

JAMA Netw Open. 2021 Nov 01. 4(11): e2133413

Association of Maternal Sexually Transmitted Infections With Risk of Preterm Birth in the United States.

Rui Gao, Buyun Liu, Wenhan Yang, Yuxiao Wu, Bo Wang, Mark K Santillan, Kelli Ryckman, Donna A Santillan, Wei Bao.

Importance: Maternal infection has been implicated in the pathogenesis of preterm birth through intrauterine inflammatory response. Chlamydia, gonorrhea, and syphilis are among the most common sexually transmitted infections worldwide, but studies on their association with preterm birth are sparse.Objective: To examine the association between maternal chlamydia, gonorrhea, and syphilis infections in pregnancy and the risk of preterm birth in a large population-based study in the US.
Design, Setting, and Participants: This population-based retrospective cohort study examined nationwide birth certificate data from the US National Vital Statistics System between 2016 and 2019. All mothers who had a singleton live birth and available data on chlamydia, gonorrhea, or syphilis infection before or during pregnancy and gestational age at birth were included in analysis.
Exposures: Sexually transmitted infection (chlamydia, gonorrhea, or syphilis) occurring before or during pregnancy.
Main Outcomes and Measures: Preterm birth, defined as gestational age less than 37 weeks.
Results: This study included 14 373 023 mothers (mean [SD] age 29 [5.8] years; Hispanic, 3 435 333 [23.9%]; non-Hispanic Asian, 912 425 [6.3%]; non-Hispanic Black, 2 058 006 [14.3%]; and non-Hispanic White, 7 386 568 [51.4%]). Among the mothers, 267 260 (1.9%) had chlamydia, 43 147 (0.3%) had gonorrhea, and 16 321 (0.1%) had syphilis. Among the newborns, 1 146 800 (8.0%) were preterm births. The rate of preterm birth was 9.9%, 12.2%, and 13.3% among women with chlamydia, gonorrhea, and syphilis infection, respectively. After adjustment for sociodemographic and medical and/or health factors, the adjusted odds ratio of preterm birth was 1.03 (95% CI, 1.02-1.04) for chlamydia, 1.11 (95% CI, 1.08-1.15) for gonorrhea, 1.17 (95% CI, 1.11-1.22) for syphilis, and 1.06 (95% CI, 1.05-1.07) for any of these sexually transmitted infections comparing mothers with these conditions and those without.
Conclusions and Relevance: Maternal sexually transmitted infections (gonorrhea, syphilis, or chlamydia) were associated with an increased risk of preterm birth. Pregnant women with sexually transmitted infections before or during pregnancy might benefit from targeted prevention for preterm birth.

DOI: https://doi.org/10.1001/jamanetworkopen.2021.33413

Clin Med (Lond). 2021 Nov;21(6): e682-e683

Haemophagocytic lymphohistiocytosis in pregnancy.

Bethan Goulden, Taryn Youngstein, Ian Giles, Jessica J Manson, David Williams.

DOI: https://doi.org/10.7861/clinmed.Let.21.6.2