Mouse Surgical Model of Mechanical Uterine Injury and Subsequent Embryo Defects

Abstract Uterine injury from procedures such as Cesarean sections (C‐sections) often have severe consequences on subsequent pregnancies, leading to disorders such as uterine placenta previa, placenta accreta spectrum (PAS), and Cesarean scar pregnancy. With rates of C‐section at ∼30% of deliveries in the US and projected to continue to climb, an understanding of the mechanisms by which these pregnancy disorders arise and opportunities for intervention are sorely needed. However, there are currently very few animal models of uterine injury and its subsequent impacts on maternal as well as in utero and postnatal fetal outcomes. Here, we describe a procedure for a novel model of surgically induced uterine injury in the genetically tractable laboratory mouse ( Mus musculus ). We describe preparatory steps for surgery, the induction of uterine injury itself, and post‐surgical recovery. We then provide supporting information regarding downstream dissection of pregnant mice. Lastly, we include additional information regarding estrous cycle staging in order to perform surgeries and dissections at the relevant phase in non‐pregnant mice. This procedure for incurring uterine injury in a mouse model presents an important step forward in understanding uterine damage and its associated pregnancy disorders. © 2024 Wiley Periodicals LLC. Basic Protocol 1 : Preparation for surgery Basic Protocol 2 : Surgery and induction of uterine injury Basic Protocol 3 : Mating and dissection of pregnant mice as endpoint analyses Support Protocol : Estrous staging of animals