Uterine scar leads to adverse pregnant consequence through impairing the response of endometrium to steroids.

Uterine surgical scar has been an increasing risk factor for adverse pregnant consequences that threatens fetal-maternal health. By far the detailed molecular features of the scar implantation remains largely lacking. To study the pathologic features of uterine surgical scar and the mechanisms of compromised pregnancy outcomes of scar implantation. We generated a mouse model of uterine surgical scar with a uterine incision penetrating myometrium to endometrium. By examining the pathologic change and transcriptome profiles of uterine scar at various post-surgery (PS) time points, as well as the features of feto-maternal interface during scar implantation. We found uterine surgical scar recovery was consistently poor at PS3 till PS90, as presented by reduced number of endometrial glands, inhibition of myometrial smooth muscle cell growth but excessive collagen fiber deposition, and massive leukocytes infiltration. Transcriptome annotation indicated significant chronic inflammation in scarring site. At peri- and post-implantation stages, abnormal expression of various steroid-responsive genes in scarring site was in parallel with lumen epithelial cell hyperplasia, inappropriate luminal closure and disorientation of implanted embryo, restricted stromal cell proliferation and defective decidualization. High embryonic lethality (around 70%) before E10.5 was observed, and the small amount of survival embryos at E10.5 exhibited restricted growth and aberrant placenta defects including over-invasion of trophoblast cells into decidua and insufficient fetal blood vessel branching in labyrinth. The findings indicate that chronic inflammation and compromised responses to steroids in uterine scar tissues are pivotal molecular basis for adverse pregnancy consequences of scar implantation.