Role of transcription factor Runx1 in uterine stromal cell differentiation and maternal-fetal interaction during mouse pregnancy

The differentiation of endometrial stromal cells to decidual cells, a process known as decidualization, is essential for the establishment of pregnancy. The decidual tissue produces multitude of factors that control a variety of physiological processes at the fetal-maternal interface, such as endometrial vasculogenesis, modulation of maternal immune response, spiral artery modification and trophoblast invasion. An aberrant decidual response is associated with various pregnancy disorders, including spontaneous miscarriage, intrauterine growth restriction and preeclampsia. Our study revealed that the expression of Runx1, a transcription factor belonging to the runt-domain family, is markedly elevated in the uterine stromal cells during decidualization. Conditional deletion of the uterine Runx1 gene led to severe embryo growth retardation and pregnancy loss during mid-gestation. Histological analysis of the Runx1-null uteri at gestation days 10-12 revealed an abnormally dense decidual tissue resulting from enhanced proliferation, impaired differentiation, and lack of apoptosis of stromal cells. The loss of Runx1 expression in uterine stromal cells also resulted in a marked impairment in the development of maternal blood vessels concomitant with a marked down regulation of several angiogenic factors, such as VEGF-A and angiopoietin-2. Furthermore, immunohistochemical analysis of smooth muscle actin and cytokeratin in the uterine sections of the mutant mice revealed a lack of maternal spiral artery modification and restricted trophoblast invasion. Collectively, these studies demonstrated that in the absence of Runx1 the decidua fails to produce critical factors that impact blood vessel formation, spiral artery modification, stromal apoptosis, and trophoblast migration. Thus, the Runx1-conditional knockout mouse presents an important animal model to study the molecular pathways that operate at the maternal-fetal interphase to control events that are critical for maintenance of pregnancy.

Name thesis:degree_name

M.S.

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

VMS - Comparative Biosciences

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2013

Author dc:creator

• Athilakshmi, Kannan

Contributors dc:contributor

• Bagchi, Indrani C.

• Decidualization
• differentiation
• Proliferation
• Angiogenesis
• spiral artery modification
• trophoblast migration
• maternal-fetal interaction.

Statement dc:rights

• Copyright 2013 Kannan Athilakshmi

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/44752

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/44752