Secretory phospholipase A2-X ( Pla2g10 ) is a novel progesterone receptor target gene exclusively induced in uterine lum
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Cell & Bioscience Open Access
RESEARCH
Secretory phospholipase A2‑X (Pla2g10) is a novel progesterone receptor target gene exclusively induced in uterine luminal epithelium for uterine receptivity in mice Hee Kyoung Park1,3, So Hee Park1, Miji Lee1, Gyeong Ryeong Kim1, Mira Park1, Seung Chel Yang1, Yeon Sun Kim1, Hyunjung J. Lim2, Hye‑Ryun Kim1* and Haengseok Song1*
Abstract Background: Aberration of estrogen (E2) and/or progesterone (P4) signaling pathways affects expression of their tar‑ get genes, which may lead to failure of embryo implantation and following pregnancy. Although many target genes of progesterone receptors (PRs) have been identified in uterine stroma, only a few PR targets have been reported in the epithelium. Secretory phospholipase A2-(PLA2)-X, a member of the PLA2 family that releases arachidonic acids for the synthesis of prostaglandins that are important for embryo implantation, is dysregulated in the endometrium of patients suffering from repeated implantation failure. However, it is not clear whether s PLA2-X is directly regulated by ovarian steroid hormones for embryo implantation in the uterus. Result: P4 induced the Pla2g10 encoding of secretory PLA2-X in the apical region of uterine LE of ovariectomized mice via PR in both time- and dose-dependent manners, whereas E2 significantly inhibited it. This finding is consist‑ ent with the higher expression of Pla2g10 at the diestrus stage, when P 4 is elevated during the estrous cycle, and at P4-treated delayed implantation. The level of Pla2g10 on day 4 of pregnancy (day 4) was dramatically decreased on day 5, when PRs are absent in the LE. Luciferase assays of mutagenesis in uterine epithelial cells demonstrated that four putative PR response elements in a Pla2g10 promoter region are transcriptionally active for Pla2g10. Intrauterine delivery of small interfering RNA for Pla2g10 on day 3 significantly reduced the number of implantation sites, reinforc‑ ing the critical function(s) of Pla2g10 for uterine receptivity in mice. Conclusions: Pla2g10 is a novel PR target gene whose expression is exclusively localized in the apical region of the uterine LE for uterine receptivity for embryo implantation in mice. Keywords: Pla2g10, Progesterone receptor, Uterine epithelium, Uterine receptivity, Embryo implantation
*Correspondence: [email protected]; [email protected] † Hee Kyoung Park and So Hee Park contributed equally to this work 1 Department of Biomedical Science, CHA University, Gyeonggi‑do, Seongnam‑si 13488, Republic of Korea Full list of author information is available at the end of the article
Background It is well understood that prostaglandins (PGs) are critical for sequential events of female reproduction from ovulation to parturition [1–3]. PGs are generated from arachidonic acid (AA) by phospholipase A2s (PLA2s) followed by cyclooxygenases. PLA2 enzymes are classified into two groups, cytosolic and secretory. Cytosolic PLA2s (cPLA2s), which are regulated by C a2+-dependent
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