Abstract
PRSS23 and PRSS35 are homologous proteases originally identified in mouse ovaries. In the periimplantation mouse uterus, Prss23 was highly expressed in the preimplantation gestation day 3.5 (D3.5) uterine luminal epithelium (LE). It disappeared from the postimplantation LE and reappeared in the stromal compartment next to the myometrium on D6.5. It was undetectable in the embryo from D4.5 to D6.5 but highly expressed in the embryo on D7.5. Prss35 became detectable in the uterine stromal compartment surrounding the embryo on D4.5 and shifted towards the mesometrial side of the stromal compartment next to the embryo from D5.5 to D7.5. In the ovariectomized uterus, Prss23 was moderately and Prss35 was dramatically downregulated by progesterone and 17β-estradiol. Based on the expression of Prss35 in granulosa cells and corpus luteum of the ovary and the early pregnant uterus, we hypothesized that PRSS35 might play a role in female reproduction, especially in oocyte development, ovulation, implantation, and decidualization. This hypothesis was tested in Prss35(−/−) mice, which proved otherwise. Between wild type (WT) and Prss35(−/−) mice, superovulation of immature females produced comparable numbers of cumulus-oocyte complexes; there were comparable numbers of implantation sites detected on D4.5 and D7.5; there were no obvious differences in the expression of implantation and decidualization marker genes in D4.5 or D7.5 uteri. Comparable mRNA expression levels of a few known protease-related genes in the WT and Prss35(−/−) D4.5 uteri indicated no compensatory upregulation. Comparable litter sizes from WT × WT and Prss35 (−/−)× Prss35 (−/−) crosses suggested that Prss35 gene was unessential for fertility and embryo development. Prss35 gene has been linked to cleft lip/palate in humans. However, no obvious such defects were observed in Prss35(−/−) mice. This study demonstrates the distinct expression of Prss23 and Prss35 in the periimplantation uterus and the dispensable role of Prss35 in fertility and embryo development.
Highlights
Proteases (.600) are categorized into five main groups: metallo, serine, cysteine, aspartic/glutamate, and threonine based on the nature of their active-site catalytic residue
The expression level of Prss23 was greatly decreased from luminal epithelium (LE) in the D4.5 wild type (WT) uterus and it was undetectable in other uterine compartments (Fig. 1C)
It was detected in the LE of the D3.5 and the D4.5 Lpar3(2/2) uteri (Figs. 1B, 1D), which had delayed uterine receptivity for embryo implantation [7]
Summary
Proteases (.600) are categorized into five main groups: metallo, serine, cysteine, aspartic/glutamate, and threonine based on the nature of their active-site catalytic residue. PRSS35 was originally identified as a novel mouse ovaryselective gene using suppression subtractive hybridization and PRSS23 was subsequently identified as a homologous protease of PRSS35 via BLAST search [4]. Both genes have two exons with the coding region in exon 2. The canonical Ser is replaced by a threonine (Thr) in PRSS35 [4] Despite their high sequence homology, Prss and Prss have their unique expression and regulation patterns in the mouse ovary [4,5]. Prss mRNA is localized in the theca layers of developing follicles, granulosa cells of preovulatory and ovulatory follicles, and the forming and regressing corpus luteum. Prss expression is progesterone-dependent prior to follicle rupture and upregulated by gonadotropins; while Prss expression is independent of progesterone and downregulated by gonadotropins
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