Abstract
Asherman's Syndrome is characterized by intrauterine adhesions or fibrosis resulting as a consequence of damage to the basal layer of endometrium and is associated with infertility due to loss of normal endometrium. We have previously shown that bone marrow derived stem cells (BMDSCs) engraft the endometrium in mice and humans and Ischemia/reperfusion injury of uterus promoted BMDSCs migration to the endometrium; however, the role of BMDSCs in Asherman's syndrome has not been characterized. Here a murine model of Asherman's syndrome was created by traumatizing the uterus. We evaluate stem cell recruitment and pregnancy after BMDSCs transplantation in a model of Asherman's syndrome. In the Asheman's syndrome model, after BMDSC transplant, the Y chromosome bearing CD45-cells represented less than 0.1% of total endometrial cells. Twice the number of Y+CD45- cells was identified in the damaged uterus compared to the uninjured controls. There was no significant difference between the damaged and undamaged uterine horns in mice that received injury to a single horn. In the BMDSC transplant group, 9 of the 10 mice conceived, while only 3 of 10 in the non-transplanted group conceived (Chi-Square p = 0.0225); all mice in an uninjured control group conceived. The time to conception and mean litter size were not different between groups. Taken together, BMDSCs are recruited to endometrium in response to injury. Fertility improves after BMDSC transplant in Asherman's Syndrome mice, demonstrating a functional role for these cells in uterine repair. BMDSC transplantation is a potential novel treatment for Asherman's Syndrome and may also be useful to prevent Asherman's syndrome after uterine injury.
Highlights
Asherman’s Syndrome is characterized by intrauterine adhesions or fibrosis resulting as a consequence of damage to the basal layer of endometrium
We have recently shown that Ischemia/reperfusion injury to the uterus promotes bone marrow derived stem cells (BMDSCs) migration to and engraftment in the endometrium; BMDSCs are recruited to the endometrium in response to injury
The histologic evidence of fibrosis was confirmed in the uterus. (Figure 1) Fibrosis varied from 40% to 80% in each mouse
Summary
Asherman’s Syndrome is characterized by intrauterine adhesions (synechiae) or fibrosis resulting as a consequence of damage to the basal layer of endometrium. This disease often leads to hypomenorrhoea or amenorrhoea, infertility or recurrent pregnancy loss. Asherman’s syndrome occurs most commonly as a result of trauma or infection, after pregnancy when estradiol levels are low. [3,4] The clinical symptoms depend on the degree and the localization of endometrial damage in the uterine cavity. [5] severe damage to the basal layer may not be amenable repair due to loss of most endometrial cells; the endometrium may fail to regenerate. Treatment is difficult and the prognosis is usually poor
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