Murine models of advanced maternal age: a systematic review and meta-analysis

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Abstract

Advanced maternal age (AMA; ≥35 years of age) is associated with increased risk of adverse pregnancy outcomes. To explore causes of adverse pregnancy outcome in AMA, and to test candidate therapies, an increasing number of murine AMA models have been developed. The aim of this study was to systematically review the literature to assess whether murine AMA models demonstrate a reproducible effect on pregnancy outcome. PubMed, Ovid, Web of Science and Google Scholar were searched. Studies that reported on pregnancy outcome in AMA mice and rats were included; the SYRCLE tool evaluated risk of bias. Eleven mouse and six rat studies were included. AMA mice and rats had reduced litter size (Standardised mean difference (SMD) -1.59, 95% CI -1.84, -1.34 for mice; SMD -1.66, 95% Confidence Interval (CI) -2.09, -1.23 for rats) and reduced fetal weight (SMD -0.87, 95% CI -1.24, -0.49 for mice; SMD -1.05, 95% CI -1.40, -0.69 for rats). Placental weight was increased in AMA mice (SMD 0.62, 95% CI 0.16, 1.08). Sub-group analysis indicated that C57Bl/6 mice had less heterogeneity than other, mostly outbred, mouse strains with regards to litter size (C57 strain I2=68.2% vs other strain types I2=85.7%). Risk of bias was high, mostly due to lack of methodological detail and unclear reporting of findings. Murine models of AMA demonstrate similar adverse pregnancy outcomes to those observed in large human epidemiological studies. The reproducible phenotypes in AMA murine models allow exploration of mechanisms underpinning poor pregnancy outcome and the pursuit of therapeutic interventions.
Original languageEnglish
JournalReproduction
Early online date1 Aug 2023
DOIs
Publication statusE-pub ahead of print - 1 Aug 2023

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