Uterine factors essential in embryo implantation are also associated with ectopic implantations

Abstract

Implantation is fundamental to successful establishment of both the trophoblast (placenta) and embryo. Free-floating cells originating from the oviduct and uterus leads to benign ectopic lesions (endosalpingiosis, ES and endometriosis, EM respectively) and may also play a role in the pathogenesis of other ectopic implantations. We hypothesized that mechanisms driving ES will give crucial insight into early pregnancy implantations and failures, including recurrent pregnancy loss, placenta accrete spectrum, and ectopic pregnancies. To fully test this hypothesis, we developed a novel mouse model to interrogate the role of implantation signaling factors in promoting non-cancerous ectopic lesions. We developed an animal model of ES using auto-fluorescing (inherent in the donor mouse cells) oviductal tissue. To test how implantation factors affect ES and EM development donor mice were treated daily with progesterone from postnatal day 2-10 to induce infertility by blocking implantation (progesterone-induced uterine gland knock out, PUGKO). Oviductal and endometrial tissue from PUGKO and vehicle control (VC) mice was harvested. Recipient mice received either oviductal or endometrial tissue alone or co-injected with endometrial tissue (non-auto-fluorescing) to reintroduce implantation factors. After a month, recipient mice were euthanized to count auto-fluorescing legions. PUGKO endometrium had significantly reduced implantation (2.14 lesions/mouse (L/M), p=0.042) compared to VC (4.71 L/M, figure 1). PUGKO endometrium with WT endometrium restored implantation. Additionally, oviduct implantation (0.92 L/M, p=0.028) was significantly increased when injected with WT endometrium (2.75 L/M, figure 2). Implantation factors are crucial to initiate and promote ectopic tissue growth. Our novel mouse model demonstrates that the removal of endometrial implantation factors reduces ectopic growth. Adding implantation factors increases oviductal tissue implantation. This model allows us to study the of implantation of these lesions, yielding the development of novel therapies.View Large Image Figure ViewerDownload Hi-res image Download (PPT)