Global gene profiling analysis of mouse uterus during the oestrous cycle

Abstract

Many genes related to the cyclic changes of the uterus during the oestrous cycle have been identified using a oneby-one approach. In the present study, cDNA microarray technology was applied to investigate the global profile of gene expression of mouse uterus at the oestrous and dioestrous stages. At a certain stage of the oestrous cycle, the uteri of mature CD-1 mice (n = 10) were removed, pooled and snap-frozen in liquid nitrogen. Total RNA was extracted to synthesize cDNA probes for microarray assay. By screening 8192 mouse genes and expressed sequence tags (ESTs), 51 upregulated and 51 downregulated genes were identified in oestrous uterus, of which 62 are well characterized and 40 are ESTs. The known genes were assigned to various gene categories according to their main function. The microarray was performed three times with three independent sets of uterine tissue pools. The results of northern blot analysis for small proline-rich protein 2 (Sprr2), 17␤-hydroxysteroid dehydrogenase type 2 (17␤HSD-2), high mobility group 2 (Hmg2), mitotic checkpoint component 2 (Mad2) and an EST AW555366 mRNA were consistent with that of microarray analysis. In situ hybridization was performed to localize the transcript of the EST AW555366. Most of the upregulated genes encode secreted immunerelated proteins, proteinases and their inhibitors, indicating their potential involvement in sperm viability as well as capacitation. The downregulated genes mainly encode cell cycle-related factors, implying the active proliferation of uterus at dioestrus.

Changes in Mouse Uterine Transcriptome in Estrus and Proestrus1

“…The serine protease cluster includes kallikrein 1 and several related peptidases, all of which were downregulated in estrus relative to proestrus (Supplemental Table S20B). Kallikrein 1 is downregulated in estrus relative to diestrus [6] and is increased by estrogen treatment [31]. Consistent with this, kallikrein 1 was upregulated in proestrus, i.e., when estrogen levels are high.…”

“…In addition, the expression of metalloproteinases (MMPs) increases toward the late-secretory phase [4] and decreases in the late proliferative phase [5]. The proliferative phase affects cellular proliferation and differentiation, extracellular matrix remodeling, angiogenesis, and vasculogenesis [5,6]. Genes related to adhesion and ion channels are also highly expressed at this phase [5].…”

“…Major changes in uterine gene expression may occur during the estrus cycle; however, our current knowledge of these changes is limited. The most complete assessment identified 61 mouse genes showing differential expression in estrus compared to diestrus, including several immune function, proteinase, and cell cycle genes [6]. Other studies examined changes in the expression of individual genes during the estrus cycle [8][9][10][11][12], including circadian clock genes [10] and genes associated with implantation [8].…”

Epithelial cells are the major site of hydroxysteroid (17β) dehydrogenase 2 and androgen receptor expression in fetal mouse lungs during the period overlapping the surge of surfactant

“…Endometrium [21,22], placenta, and liver [23] were included as positive controls for the detection of HSD17B2. Immunohistochemistry with the three anti-HSD17B2 antibodies on mouse endometrial tissues showed a strong positive signal specifically on epithelial cells, as expected (data not shown).…”

Differential Expression of Wnt Signaling Molecules Between Pre- and Postmenopausal Endometrial Epithelial Cells Suggests a Population of Putative Epithelial Stem/Progenitor Cells Reside in the Basalis Layer

“…Highly prominent genes in this category were the cell proliferation regulator, RXRA, whose expression was expected in atrophic glands (43,44), a tissue remodeling gene ADAMST1 and an estrogen-modulated gene, DMBT1, essential for epithelial proliferation and regeneration (45,46). The annotation of these highly expressed genes in Post-M endometrium suggests their possible functional role in regulating endometrial epithelial cell proliferation in the basalis of Pre-M and their potential roles in regulating putative resident ESP cells.…”