Evidence map›Paper›PMID 28193233›Full record

ArticleJournal of translational medicine2017

Tacrolimus in the prevention of adverse pregnancy outcomes and diabetes-associated embryopathies in obese and diabetic mice.

Ahmad J H Albaghdadi, Melanie A Hewitt, Samantha M Putos, Michael Wells, Terence R S Ozolinš, Frederick W K Kan

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In one paragraph

Article in Journal of translational medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Ahmad J H AlbaghdadiDepartment of Biomedical and Molecular Sciences, Faculty of Health Sciences, Queen's University, Kingston, ON, K7L3N6, Canada.
Melanie A HewittDepartment of Biomedical and Molecular Sciences, Faculty of Health Sciences, Queen's University, Kingston, ON, K7L3N6, Canada.
Samantha M PutosDepartment of Biomedical and Molecular Sciences, Faculty of Health Sciences, Queen's University, Kingston, ON, K7L3N6, Canada.
Michael WellsPARTEQ Innovations, Queen's University, Kingston, ON, K7L 0E9, Canada.
Terence R S OzolinšDepartment of Biomedical and Molecular Sciences, Faculty of Health Sciences, Queen's University, Kingston, ON, K7L3N6, Canada.
Frederick W K KanDepartment of Biomedical and Molecular Sciences, Faculty of Health Sciences, Queen's University, Kingston, ON, K7L3N6, Canada. kanfwk@queensu.ca.ORCID 0000-0003-0026-9061

Funding

CIHR MOP93606
6 · The paper itself

Abstract

backgroundT2DM is a high-risk pregnancy with adverse fetal and maternal outcomes including repeated miscarriages and fetal malformations. Despite the established association between placental insufficiency and poor maternal Th1-adaptability to the development of pregnancy complications in T2DM, there have been no established data to assess benefits of pre-pregnancy immunosuppression relative to gestational outcomes in T2DM. We hypothesized that pre-pregnancy macrolide immune suppression can re-establish normal placental development and uterine vascular adaptation in a mouse model of obesity-associated T2DM.

methodsFetal live birth rate, postnatal variability, mid-gestational uterine and umbilical flow dynamics and certain morphological features of spiral artery modification were examined in the New Zealand Obese (NONcNZO10/Ltj) female mice (n = 56) weaned to ages of 32 weeks on a 60% calories/g high-fat diet (also referred to as HFD-dNONcNZO), and which received either tacrolimus (0.1 mg/kg s.c. q2d) , its vehicle (castor oil and ethanol) or metformin (in drinking water 200 mg/dL p.o. ad libitum). HFD-BALBc-Rag2/IL2-gc female mice (n = 24) were used as HFD-immunodeficient controls.

resultsTreatment of the HFD-dNONcNZO female mice with tacrolimus improved live birth rates and postnatal viability scores (p < 0.01), normalized OGTT (p < 0.001), inhibited fetal malformation rates, restored morphology of spiral arterial modification; and improved uterine arterial and umbilical blood flow (p < 0.01). Placental production of TNFαand IL16 in the tacrolimus-treated HFD-dNONcNZO dams were restored to non-diabetic levels and the treatment resulted in the inhibition of aberrant monocyte/macrophage activation during pregnancy in the HFD-dNONcNZO dams.

conclusionsOur present data suggest a casual association between chronic maternal overnutrition and aberrancy in the maternal Th1-immune maladaptation to pregnancy and defective spiral artery modification, placental insufficiency and adverse fetal outcomes in the T2DM subjects. Further safety studies into the use of tacrolimus in the pre-pregnancy glycemic control may be beneficial.

Indexed as

Pregnancy OutcomeAnimalsBone and BonesDiabetes Mellitus, ExperimentalDiet, High-FatFemaleFetal DiseasesGlucose Tolerance TestMetforminMice, Inbred BALB CMice, ObesePregnancySpineTacrolimusUmbilical CordUterine ArteryMetforminTacrolimusAdverse pregnancy outcomes (APO)DiabetesEmbryopathiesImmunosuppressionMetforminTacrolimus

Identifiers

PMID28193233
PMCPMC5307666

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.