CRISPLD2 Is a Target of Progesterone Receptor and Its Expression Is Decreased in Women with Endometriosis

Abstract

Endometriosis, defined as the presence of endometrial cells outside of the uterine cavity, is a major cause of infertility and pelvic pain, afflicting more than 10% of reproductive age women. Endometriosis is a chronic inflammatory disease and lipopolysaccharide promotes the proliferation and invasion of endometriotic stromal cells. Cysteine-rich secretory protein LCCL domain-containing 2 (CRISPLD2) has high affinity for lipopolysaccharide and plays a critical role in defense against endotoxin shock. However, the function of CRISPLD2 has not been studied in endometriosis and uterine biology. Herein, we examined the expression of CRISPLD2 in endometrium from patients with and without endometriosis using immunohistochemistry. The expression of CRISPLD2 was higher in the secretory phase in human menstrual cycle compared to proliferative phase. The expression of CRISPLD2 was significantly decreased in the endometrium of women with endometriosis in the early secretory phase compared to women without endometriosis. The increase of CRISPLD2 expression at the early secretory and dysregulation of its expression in endometriosis suggest progesterone (P4) regulation of CRISPLD2. To investigate whether CRISPLD2 is regulated by P4, we examined the expression of the CRISPLD2 in the uteri of wild-type and progesterone receptor knock out (PRKO) mice. The expression of CRISPLD2 was significantly increased after P4 treatment in the wild-type mice. However, CRISPLD2 expression was significantly decreased in the (PRKO) mice treated with P4. During early pregnancy, the expression of CRISPLD2 was increased in decidua of implantation and post-implantation stages. CRISPLD2 levels were also increased in cultured human endometrial stromal cells during in vitro decidualization. These results suggest that the CRISPLD2 is a target of the progesterone receptor and may play an important role in pathogenesis of endometriosis.

Gene expression profiling of upregulated mRNAs in granulosa cells of bovine ovulatory follicles following stimulation with hCG

“…Since a parallel can be drawn with the ovulatory process in which multiple ECM proteins and ECM modifying enzymes are induced (Table 2 ), we suggest that CRISPLD2 may interact with these proteins and modifying enzymes during ovulation. Interestingly, CRISPLD2 is regulated by progesterone (P4) and its receptor (PGR) in the uterus, its expression is high during decidualization, constitutive during pregnancy and is dysregulated in patients with endometriosis [ 49 ]. A similar P4/PGR-dependent regulation of CRISPLD2 gene expression has been observed in rat granulosa cells [ 50 ].…”

ARID1A Is Essential for Endometrial Function during Early Pregnancy

“…The human endometrial samples were collected from Michigan State University’s Center for Women’s Health Research Female Reproductive Tract Biorepository, the Greenville Hospital System, and the University of North Carolina. Samples were collected as previously reported [ 97 , 98 ]. Briefly, to compare gene expression patterns of eutopic endometrium between those with and without endometriosis, 28 samples were collected from proliferative, early, mid, and late secretory phases (n = 7 per phase).…”

Endometrial receptivity in the eutopic endometrium of women with endometriosis: it is affected, and let me show you why

“…Such alterations in the balance between estrogen and progesterone likely impact fertility and implantation while also promoting the pathogenesis of endometriosis as a disease (50). Progesterone receptor changes and down-stream effects of progesterone (51, 52) are noted in women with endometriosis (53). Park et al suggested that the endometrium of women with endometriosis is more proliferative as a result of endometriosis (54) and we demonstrated the endometrium displays an inappropriate elevation in secretory phase estrogen receptors (ESR1) at the time of implantation (55).…”