Abstract:
BACKGROUND:Endometriosis is recognized as a steroid-dependent disorder; however, the precise roles of nuclear receptors (NRs) in steroid responsiveness and other signaling pathways are not well understood. OBJECTIVE AND RATIONALE:Over the past several years, a number of paradigm-shifting breakthroughs have occurred in the area of NRs in endometriosis. We review and clarify new information regarding the mechanisms responsible for: (i) excessive estrogen biosynthesis, (ii) estrogen-dependent inflammation, (iii) defective differentiation due to progesterone resistance and (iv) enhanced survival due to deficient retinoid production and action in endometriosis. We emphasize the roles of the relevant NRs critical for these pathological processes in endometriosis. SEARCH METHODS:We conducted a comprehensive search using PubMed for human, animal and cellular studies published until 2018 in the following areas: endometriosis; the steroid and orphan NRs, estrogen receptors alpha (ESR1) and beta (ESR2), progesterone receptor (PGR), steroidogenic factor-1 (NR5A1) and chicken ovalbumin upstream promoter-transcription factor II (NR2F2); and retinoids. OUTCOMES:Four distinct abnormalities in the intracavitary endometrium and extra-uterine endometriotic tissue underlie endometriosis progression: dysregulated differentiation of endometrial mesenchymal cells, abnormal epigenetic marks, inflammation activated by excess estrogen and the development of progesterone resistance. Endometriotic stromal cells compose the bulk of the lesions and demonstrate widespread epigenetic abnormalities. Endometriotic stromal cells also display a wide range of abnormal NR expression. The orphan NRs NR5A1 and NR2F2 compete to regulate steroid-synthesizing genes in endometriotic stromal cells; NR5A1 dominance gives rise to excessive estrogen formation. Endometriotic stromal cells show an abnormally low ESR1:ESR2 ratio due to excessive levels of ESR2, which mediates an estrogen-driven inflammatory process and prostaglandin formation. These cells are also deficient in PGR, leading to progesterone resistance and defective retinoid synthesis. The pattern of NR expression, involving low ESR1 and PGR and high ESR2, is reminiscent of uterine leiomyoma stem cells. This led us to speculate that endometriotic stromal cells may display stem cell characteristics found in other uterine tissues. The biologic consequences of these abnormalities in endometriotic tissue include intense inflammation, defective differentiation and enhanced survival. WIDER IMPLICATIONS:Steroid- and other NR-related abnormalities exert genome-wide biologic effects via interaction with defective epigenetic programming and enhance inflammation in endometriotic stromal cells. New synthetic ligands, targeting PGR, retinoic acid receptors and ESR2, may offer novel treatment options.
journal_name
Hum Reprod Updatejournal_title
Human reproduction updateauthors
Yilmaz BD,Bulun SEdoi
10.1093/humupd/dmz005subject
Has Abstractpub_date
2019-07-01 00:00:00pages
473-485issue
4eissn
1355-4786issn
1460-2369pii
5365598journal_volume
25pub_type
杂志文章,评审abstract::Contraception is one of the keystones of reproductive health. The availability of effective contraception has helped to change dramatically the structure of the world's population during the last 50 years, through a demographic transition involving lower fertility rates and longer survival. As the transition evolves m...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/dmi019
更新日期:2005-09-01 00:00:00
abstract::After colonization of the gonad, mouse female germ cells enter into the prophase of the first meiotic division as a mid-gestational hallmark of gender. Perinatally, oocytes interact with granulosa cells to form primordial follicles which, with cyclic periodicity, enter into a 3-week growth phase that culminates in mei...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/8.5.395
更新日期:2002-09-01 00:00:00
abstract::BACKGROUND Endometriosis associated with pain symptoms in adolescents has been extensively reported, but the exact prevalence is unclear because pain symptoms may be atypical and endometriosis can only be diagnosed by laparoscopy. The aim of this paper is to provide a systematic review of the prevalence of endometrios...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/dmt016
更新日期:2013-09-01 00:00:00
abstract:BACKGROUND:Transfer of more than a single embryo in an IVF cycle comes with the finite possibility of a multiple gestation. Even a twin pregnancy confers significant risk to both mother and babies. The move to single-embryo transfer for all patients will be greatly facilitated by the ability to quantify embryo viabilit...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/dmu064
更新日期:2015-11-01 00:00:00
abstract::Great progress had been achieved during the last 20 years in the field of ovulation induction in patients with polycystic ovary syndrome (PCOS). Clomiphene citrate remains the first line of treatment for all anovulatory women with PCOS, since in properly selected patients the cumulative pregnancy rate approaches that ...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/3.3.235
更新日期:1997-05-01 00:00:00
abstract::Cryopreservation of testicular tissue might benefit prepubertal boys who must undergo chemotherapy or radiotherapy. Cryopreservation of testicular tissue and testicular cells for intracytoplasmic sperm injection (ICSI) is feasible and widely applied. Testicular tissue from prepubertal boys can also be frozen, by apply...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/7.4.378
更新日期:2001-07-01 00:00:00
abstract::Mucin glycoproteins are major constituents of the glycocalyx that covers mucosal epithelium. Two broad classes of mucins exist: membrane-associated and secretory. Of the secreted mucins, those with cysteine-rich regions are thought to polymerize through disulphide bonds. Among these gel-forming mucins are MUC2, MUC5AC...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/5.4.280
更新日期:1999-07-01 00:00:00
abstract:BACKGROUND:A dynamic balance between pro- and anti-inflammatory factors contributes to regulating human female reproduction. Chronic low-grade inflammation has been detected in several female reproductive conditions, from anovulation to embryo implantation failure. C-reactive protein (CRP) is a reliable marker of infla...
journal_title:Human reproduction update
pub_type: 杂志文章
doi:10.1093/humupd/dmaa012
更新日期:2020-09-01 00:00:00
abstract::BACKGROUND To review the accuracy of multivariate models for the prediction of ovarian reserve and pregnancy in women undergoing IVF compared with the antral follicle count (AFC) as single test. METHODS We performed a computerized MEDLINE and EMBASE search to identify articles published on multivariate models for ovar...
journal_title:Human reproduction update
pub_type: 杂志文章,meta分析
doi:10.1093/humupd/dmn001
更新日期:2008-03-01 00:00:00
abstract::Sperm transport from the cervix into the tube is an important uterine function within the process of reproduction. This function is exerted by uterine peristalsis and is controlled by the dominant ovarian structure via a cascade of endocrine events. The uterine peristaltic activity involves only the stratum subvascula...
journal_title:Human reproduction update
pub_type: 杂志文章
doi:10.1093/humupd/4.5.667
更新日期:1998-09-01 00:00:00
abstract:BACKGROUND:Activins are members of the pleiotrophic family of the transforming growth factor-beta (TGF-β) superfamily of cytokines, initially isolated for their capacity to induce the release of FSH from pituitary extracts. Subsequent research has demonstrated that activins are involved in multiple biological functions...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/dmv058
更新日期:2016-04-01 00:00:00
abstract:BACKGROUND:Because of the substantial energy demands of reproduction, the brain must temper the fertility of individuals to match nutritional availability. Under-nutrition is associated with infertility in humans and animals. The brain uses adipose- and gut-derived hormones, such as leptin, insulin and ghrelin, to modu...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/dms004
更新日期:2012-05-01 00:00:00
abstract::Laparoscopic and hysteroscopic surgery have changed the management of many gynaecological disorders. Procedures that previously required a long duration of hospitalization can now be done on an outpatient basis or with a short hospital stay. Surgical treatment remains the definitive and universal treatment of ectopic ...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/2.5.419
更新日期:1996-09-01 00:00:00
abstract:BACKGROUND:Recently, dopamine agonists were proposed as a prophylactic treatment for ovarian hyperstimulation syndrome (OHSS) in women at high risk in IVF/ICSI treatment cycles. METHODS:We conducted a systematic review and meta-analysis of randomized trials comparing the prophylactic effect of the dopamine agonist, ca...
journal_title:Human reproduction update
pub_type: 杂志文章,meta分析,评审
doi:10.1093/humupd/dmq006
更新日期:2010-09-01 00:00:00
abstract:BACKGROUND:Recurrent pregnancy loss (RPL) occurs in 1-3% of all couples trying to conceive. No consensus exists regarding when to perform testing for risk factors in couples with RPL. Some guidelines recommend testing if a patient has had two pregnancy losses whereas others advise to test after three losses. OBJECTIVE...
journal_title:Human reproduction update
pub_type: 杂志文章,meta分析
doi:10.1093/humupd/dmz048
更新日期:2020-04-15 00:00:00
abstract:BACKGROUND:Infertility is estimated to affect as many as 186 million people worldwide. Although male infertility contributes to more than half of all cases of global childlessness, infertility remains a woman's social burden. Unfortunately, areas of the world with the highest rates of infertility are often those with p...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/dmv016
更新日期:2015-07-01 00:00:00
abstract::This review provides an overview of how women adjust emotionally to the various phases of IVF treatment in terms of anxiety, depression or general distress before, during and after different treatment cycles. A systematic scrutiny of the literature yielded 706 articles that paid attention to emotional aspects of IVF t...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/dml040
更新日期:2007-01-01 00:00:00
abstract::Pregnancy induces physiological alterations in thyroid function which may make difficult the interpretation of results of thyroid hormone measurement. A state of hyperstimulation of the thyroid gland is common in early pregnancy. In a few cases, thyroid hormone values will deviate from the normal range, which correspo...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/dmh008
更新日期:2004-03-01 00:00:00
abstract:BACKGROUND:More than 15 million women, many of reproductive age, were infected with human immunodeficiency virus (HIV) at the end of 2007. As the HIV epidemic evolves, heterosexual intercourse is increasingly risky: the risk of infection in exposed young women is 4- to 7-fold higher than in young men and nearly half a ...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/dmn049
更新日期:2009-03-01 00:00:00
abstract:BACKGROUND:Infertility affects ∼7% of all men. Despite much progress, mainly in genetics, its etiology remains obscure in ∼50% of cases. To fill this gap, imaging of the male genital tract (MGT) has progressively expanded, providing useful information in the assessment of MGT abnormalities. METHODS:A critical, systema...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/dmu042
更新日期:2015-01-01 00:00:00
abstract::In the male genital tract, reactive oxygen species (ROS) are generated by spermatozoa and leukocytes including neutrophils and macrophages. ROS are involved in the regulation of sperm functions such as capacitation and the acrosome reaction. Infections lead to an excessive ROS production, resulting in an 'oxidative bu...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/5.5.399
更新日期:1999-09-01 00:00:00
abstract::The effects on reproductive tract development in male rats, of neonatal exposure to potent (reference) oestrogens, diethylstilboestrol (DES) and ethinyl oestradiol (EE), with those of two environmental oestrogens, octylphenol and hisphenol A were systematically compared. Other treatments, such as administration of a g...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/7.3.236
更新日期:2001-05-01 00:00:00
abstract:BACKGROUND:Worldwide, placenta-related complications contribute to adverse pregnancy outcomes, such as pre-eclampsia, fetal growth restriction and preterm birth, with implications for the future health of mothers and offspring. The placenta develops in the periconception period and forms the interface between mother an...
journal_title:Human reproduction update
pub_type: 杂志文章
doi:10.1093/humupd/dmy037
更新日期:2019-01-01 00:00:00
abstract::Significant association between endometriosis, including minor endometriosis, and infertility (or strictly subfertility) is shown by prevalence studies, but a causal relationship has not been established. This review focuses on evidence for pituitary-ovarian dysfunction as a cause for the subfertility. A methodologica...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/6.1.56
更新日期:2000-01-01 00:00:00
abstract:BACKGROUND:Reproductive disorders and infertility are associated with the risk of obstetric complications and have a negative impact on pregnancy outcome. Affected patients often require assisted reproductive technologies (ART) to conceive, and advanced maternal age is a further confounding factor. The challenge is to ...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/dmv044
更新日期:2016-01-01 00:00:00
abstract::Despite recent advances in ovarian stimulation regimens and laboratory techniques, the pregnancy rate of assisted reproduction remains relatively low. New methods that would potentially improve implantation rates are needed. One proposed strategy involves enhancement of blood flow at the implantation site with the use...
journal_title:Human reproduction update
pub_type: 杂志文章,meta分析,评审
doi:10.1093/humupd/dmm005
更新日期:2007-07-01 00:00:00
abstract:BACKGROUND:The main objective of individualization of treatment in IVF is to offer every single woman the best treatment tailored to her own unique characteristics, thus maximizing the chances of pregnancy and eliminating the iatrogenic and avoidable risks resulting from ovarian stimulation. Personalization of treatmen...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/dmt037
更新日期:2014-01-01 00:00:00
abstract::In those clinical situations in which an immediate and profound suppression of gonadotrophins is desired, LHRH agonists have the disadvantage of producing an initial stimulatory effect on hormone secretion. Therefore, the use of GnRH antagonists which cause an immediate and dose-related inhibition of LH and FSH by com...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/6.4.322
更新日期:2000-07-01 00:00:00
abstract::Ca(2+) is a ubiquitous intracellular messenger which encodes information by temporal and spatial patterns of concentration. In spermatozoa, several key functions, including acrosome reaction and motility, are regulated by cytoplasmic Ca(2+) concentration. Despite the very small size and apparent structural simplicity ...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/dmi050
更新日期:2006-05-01 00:00:00
abstract::Single-dose and multiple-rising dose studies of recombinant follicle stimulating hormone (rFSH) in hypogonadotrophic male and female volunteers demonstrated that the rate of FSH absorption after i.m. injection is higher in men than in women. In the absence of endogenous FSH, a correlation between serum FSH and body we...
journal_title:Human reproduction update
pub_type: 杂志文章,评审
doi:10.1093/humupd/2.2.153
更新日期:1996-03-01 00:00:00