Leukemia inhibitory factor promotes the regeneration of rat uterine horns with full thickness injury
Bai Xue MD Dan Liu PhD Minmin Song MD Guangfeng Zhao PhD Yun Cao PhD Guijun Yan PhD Jianwu Dai PhD Yali Hu PhD
First published: 20 May 2019 https://doi.org/10.1111/wrr.12729
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/wrr.12729.
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Abstract
Severe uterine injuries may lead to infertility or pregnancy complications. There is a lack of effective methods to restore the structure and function of seriously injured uteri. Leukemia inhibitory factor (LIF), which plays a crucial role in blastocyst implantation, promotes the process of regeneration after injury in several different tissues. In this study, we explored the effect of LIF on the regeneration of rat uterine horns following full thickness injury. One hundred and twenty four female Sprague‐Dawley rats were assigned to three groups, including a sham operated group (n=34 uterine horns), a PBS/collagen group (n=90 uterine horns) and a LIF/collagen group (n=124 uterine horns). The regenerated uterine horns were collected at 1, 2, 4, 8 or 12 weeks post‐surgery. The results demonstrated that LIF/collagen scaffolds increased the number of endometrial cells and neovascularization 2 weeks after uterine full‐thickness defect in excision sites (P<0.001 versus PBS/collagen). Eight weeks post‐surgery, the number of endometrial glands was dramatically higher in the LIF/collagen scaffolds group (35.2 ± 4.1/field) than in PBS/collagen scaffolds (15.1 ± 1.4/field). The percentage of a‐SMA‐positive areas in the LIF/collagen scaffolds (88.8% ± 9.8%) was also significantly higher than that in the PBS/collagen group (52.9% ± 3.7%). Moreover, LIF improved the pregnancy rate and fetus number. We also found that LIF inhibited the infiltration of inflammatory cells and down‐regulated the pro‐inflammatory cytokine IL‐12 expression while up‐regulating the anti‐inflammatory cytokine IL‐10 expression in the injured part of the uterine horns. Our results indicate that LIF promotes regeneration of the uterus after injury, and this is at least partially due to its immunomodulatory properties. In addition, it is worth to explore further the possibility for LIF/collagen to be an alternative therapeutic approach for uterine damage in the clinic in near future.
Bai Xue MD Dan Liu PhD Minmin Song MD Guangfeng Zhao PhD Yun Cao PhD Guijun Yan PhD Jianwu Dai PhD Yali Hu PhD
First published: 20 May 2019 https://doi.org/10.1111/wrr.12729
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/wrr.12729.
ePDFPDFTOOLS SHARE
Abstract
Severe uterine injuries may lead to infertility or pregnancy complications. There is a lack of effective methods to restore the structure and function of seriously injured uteri. Leukemia inhibitory factor (LIF), which plays a crucial role in blastocyst implantation, promotes the process of regeneration after injury in several different tissues. In this study, we explored the effect of LIF on the regeneration of rat uterine horns following full thickness injury. One hundred and twenty four female Sprague‐Dawley rats were assigned to three groups, including a sham operated group (n=34 uterine horns), a PBS/collagen group (n=90 uterine horns) and a LIF/collagen group (n=124 uterine horns). The regenerated uterine horns were collected at 1, 2, 4, 8 or 12 weeks post‐surgery. The results demonstrated that LIF/collagen scaffolds increased the number of endometrial cells and neovascularization 2 weeks after uterine full‐thickness defect in excision sites (P<0.001 versus PBS/collagen). Eight weeks post‐surgery, the number of endometrial glands was dramatically higher in the LIF/collagen scaffolds group (35.2 ± 4.1/field) than in PBS/collagen scaffolds (15.1 ± 1.4/field). The percentage of a‐SMA‐positive areas in the LIF/collagen scaffolds (88.8% ± 9.8%) was also significantly higher than that in the PBS/collagen group (52.9% ± 3.7%). Moreover, LIF improved the pregnancy rate and fetus number. We also found that LIF inhibited the infiltration of inflammatory cells and down‐regulated the pro‐inflammatory cytokine IL‐12 expression while up‐regulating the anti‐inflammatory cytokine IL‐10 expression in the injured part of the uterine horns. Our results indicate that LIF promotes regeneration of the uterus after injury, and this is at least partially due to its immunomodulatory properties. In addition, it is worth to explore further the possibility for LIF/collagen to be an alternative therapeutic approach for uterine damage in the clinic in near future.
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