Gene expression pattern and hormonal regulation of Small Proline-Rich Protein 2 family members in the female mouse reproductive system during the estrous cycle and pregnancy

Abstract

-Small proline-rich proteins (SPRR) are known to construct the cornified cell envelope (CE) in the stratified squamous epithelial cell. Their functions in the simple epithelium such as the uterine epithelium are not clear hitherto. In the present study, the mRNA expression patterns of sprr2 family members in the mouse uterus and vagina during the estrous cycle and pregnancy as well as their regulation by steroids were investigated. Using semi-quantitative RT-PCR, it was revealed that the transcripts of sprr2b, 2e and 2g genes were up-regulated in the proestrous and estrous uteri, and sprr2d was up-regulated only in the estrous uterus. In the vagina, transcription of sprr2a, 2b, 2d, 2e and 2k genes were up-regulated at the metestrous stage. Northern blot analysis demonstrated that the overall expression of sprr2 was highly up-regulated in the estrous uterus and the metestrous vagina. During pregnancy, the sprr2 mRNA in the uterus was sharply repressed from day 3 postcoitus on, and began to be induced around labor time. In situ hybridization showed that the sprr2 transcripts were localized in uterine luminal and glandular epithelial cells as well as vaginal stratified epithelial cells. In ovariectomized mice, the expression of sprr2a, 2d, 2e and 2f genes in the uterus were induced by estrogen, and the effect of estrogen on sprr2d and 2e expression could be partly abolished by progesterone. The data indicate that the sprr2 genes have unique regulation patterns in different reproductive tissues under different physiological conditions, and the encoded proteins might play diverse functions in the female reproductive system. small proline-rich protein / uterus / estrous cycle / pregnancy / stress

Uterine inactivation of muscle segment homeobox (Msx) genes alters epithelial cell junction proteins during embryo implantation

“…However, Sprr2 expression was observed in epithelial cells lining the antimesometrial side of the implantation chamber on d 5 in Msx1 f/f /Msx2 f/f females. Our observation of high Sprr2 expression on d 1 with substantially reduced levels on d 2–5 are consistent with previously published data obtained by Northern blot analysis of whole uterine extracts; however, Sprr2 expression at the implantation sites had not been reported, which may be because of a difference in the timing of collection (d 4 2200 h vs. d 5, 1030 h) (30). In Msx1 d/d /Msx2 d/d uteri, in situ hybridization of Sprr2 showed strong signal on d 1 that was indistinguishable from WT levels.…”

Lkb1inactivation is sufficient to drive endometrial cancers that are aggressive yet highly responsive to mTOR inhibitor monotherapy

“…Sprr2 family members are variably expressed in different organs such as the skin and esophagus, where their expression is confined to the squamous or columnar epithelial cells (Patel et al, 2003;Song et al, 1999). Sprr2 gene expression in the female reproductive tract had been documented previously, but the uterine-specific expression of Sprr2f was not known prior to this study (Hong et al, 2004;Tan et al, 2003;Tan et al, 2006). To understand the basis of the observed estrogen dependence of Sprr2f expression, the 4 kbs of genomic sequence upstream of each transcriptional start site were scanned with the Dragon ERE (estrogen response element) finder (Bajic et al, 2003).…”

Integrated chromatin immunoprecipitation sequencing and microarray analysis identifies FOXA2 target genes in the glands of the mouse uterus

“…Many of the genes increased in expression in the Foxa2 ‐deleted uteri are expressed in the endometrial LE in the adult uterus, including Clca3, Prap1, and Sprr2 family (45, 46). Intriguingly, small proline‐rich proteins (SPRRs) construct the cornified cell envelope in the stratified squamous epithelial cells of tissues such as the vagina, but are also expressed in the uterine LE and GE (47). Thus, the up‐regulation of the Sprr2 genes and other keratin genes may render the LE unable to mediate blastocyst attachment for implantation, which could be part of the implantation defect observed in conditional Foxa2 ‐deleted mice as well as progesteroneinduced uterine gland knockout mice.…”