CRISPLD2 is a target of progesterone receptor and its expression is decreased in women with endometriosis.

Jung-Yoon Yoo,Un-Hwan Ha,Jae-Wook Jeong,Tae Hoon Kim,Asgerally T Fazleabas,Heesung Shin,Won-Seok Choi,Bruce A Lessey,Susan D Ferguson,Steven L Young

doi:10.1371/journal.pone.0100481

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.

Highlights

Endometriosis is one of the most common causes of chronic pelvic pain and infertility
To determine if CRISPLD2 is dysregulated in endometriosis, we examined the expression of CRISPLD2 in endometrium from early secretory phase women with and without endometriosis using immunohistochemistry
The protein level of CRISPLD2 was significantly lower in the eutopic endometrium obtained during the secretory phase from women with endometriosis compared to cells from the control endometrium (Fig. 2)

Summary

Introduction

Endometriosis is one of the most common causes of chronic pelvic pain and infertility. It affects 10% of women of reproductive age and the incidence increases to 35–50% in infertile women [1,2]. The initiation of endometriosis is difficult to evaluate because the disease has usually been prevalent for 8–11 years at the time of clinical diagnosis [2,3]. Endometriosis is a multifactorial disease [4]. One of the major hallmarks of these uterine diseases is disruption of steroid hormone control of uterine cell proliferation and differentiation [5]. Elucidating the molecular mechanisms by which the steroid hormones control uterine physiology is paramount to understanding the pathology of these diseases

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Results

Conclusion