A Novel Class of Interstitial Cells in the Mouse and Monkey Female Reproductive Tracts1

Abstract

Growing evidence suggests important roles for specialized platelet-derived growth factor receptor alpha-positive (PDGFRalpha(+)) cells in regulating the behaviors of visceral smooth muscle organs. Examination of the female reproductive tracts of mice and monkeys showed that PDGFRalpha(+) cells form extensive networks in ovary, oviduct, and uterus. PDGFRalpha(+) cells were located in discrete locations within these organs, and their distribution and density were similar in rodents and primates. PDGFRalpha(+) cells were distinct from smooth muscle cells and interstitial cells of Cajal (ICC). This was demonstrated with immunohistochemical techniques and by performing molecular expression studies on PDGFRalpha(+) cells from mice with enhanced green fluorescent protein driven off of the endogenous promoter for Pdgfralpha. Significant differences in gene expression were found in PDGFRalpha(+) cells from ovary, oviduct, and uterus. Differences in gene expression were also detected in cells from different tissue regions within the same organ (e.g., uterine myometrium vs. endometrium). PDGFRalpha(+) cells are unlikely to provide pacemaker activity because they lack significant expression of key pacemaker genes found in ICC (Kit and Ano1). Gja1 encoding connexin 43 was expressed at relatively high levels in PDGFRalpha(+) cells (except in the ovary), suggesting these cells can form gap junctions to one another and neighboring smooth muscle cells. PDGFRalpha(+) cells also expressed the early response transcription factor and proto-oncogene Fos, particularly in the ovary. These data demonstrate extensive distribution of PDGFRalpha(+) cells throughout the female reproductive tract. These cells are a heterogeneous population of cells that are likely to contribute to different aspects of physiological regulation in the various anatomical niches they occupy.

Calcium Signaling in Interstitial Cells: Focus on Telocytes

“…It is distinct from smooth muscle cells and ICCs, and was characterized to have a variable gene expression between parts of the reproductive tract (e.g., ovary, oviduct, and uterus) or between the tissue regions of the same organ (e.g., uterine myometrium vs. endometrium) [ 131 ]. These cells are unlikely to provide pacemaker activity, as key pacemaker genes found in ICCs (e.g., Kit , and Ano1 ) [ 121 , 132 ] were not detected to be expressed, while the Gja1 gene encoding for connexin 43 was identified in high levels suggesting their possible involvement in forming gap junctions in between and with the neighboring smooth muscle cells [ 131 ]. CD34 and PDGFRα are considered as reliable markers to identify and separate TCs [ 47 , 133 , 134 ] and we might suppose that the newly identified interstitial cells are corresponding to TCs.…”

“…Oppositely to the uterine TCs that do not express the pacemaker-related Kit and Ano1 genes [ 131 ], cardiac TCs express CD34, CD29, vimentin, sca-1, c-kit, and Nanog, and are more likely to be involved in the heart pacemaking activity [ 133 , 139 , 140 ]. Additionally, cardiac TCs were demonstrated to functionally express large conductance Ca 2+ -activated K + currents (BKCa) and inwardly rectifying K + currents, but not transient outward K + currents or ATP-sensitive potassium current [ 124 ].…”

Ca2+ signalling in mouse urethral smooth muscle in situ: role of Ca2+ stores and Ca2+ influx mechanisms

“…; Peri et al . ), Myh11 (myosin heavy chain; smooth muscle cells), Uch11 encoding PGP 9.5 (nerve cells) and Tpsab1 ( mast cell tryptase). Enriched USMCs isolated from SMC‐eGFP + mice showed minimal expression of these genes with the exception of the smooth muscle marker Myh11 (Fig.…”

Uterine contractions in rodent models and humans

“…Several groups have sought to find an "ICC-like cell" in the uterus, searching for interstitial cells that produce similar slow waves or express similar membrane markers. So-called ICC-like cells have been found in the uterus of humans, rats, mice, and monkeys, [116][117][118][119][120] but thus far, no group has definitively shown that these cells are capable of producing slow waves in isolation. Furthermore, myometrial cells may not exhibit the slow waves seen in the gut.…”