Spaceflight induces changes in gene expression profiles linked to insulin and estrogen.

Organismal adaptations to spaceflight have been characterized at the molecular level in model organisms, including Drosophila and C. elegans. Here, we extend molecular work to energy metabolism and sex hormone signaling in mice and humans.

Society of Radiologists in Ultrasound Consensus on Routine Pelvic US for Endometriosis.

Endometriosis is a prevalent and potentially debilitating condition that mostly affects individuals of reproductive age, and often has a substantial diagnostic delay. US is usually the first-line imaging modality used when patients report chronic pelvic pain or have issues of infertility, both common symptoms of endometriosis. Other than the visualization of an endometrioma, sonologists frequently do not appreciate endometriosis on routine transvaginal US images.

Transcriptomic changes in eutopic endometrium and ectopic lesions during endometriosis progression in a mouse model.

Objective: To identify the transcriptomic changes of ectopic lesions and eutopic endometrial tissues during the progression of endometriosis, we performed transcriptomic analysis in the eutopic endometrium and ectopic lesions.

Design: Laboratory study.

Setting: Academic medical center.

Uterine Uptake of Estrogen and Progestogen-Based Radiotracers in Rhesus Macaques with Endometriosis.

Purpose: Endometriosis is an estrogen-dependent disorder of menstruating primates where tissues similar to the inner lining of the uterus exist "ectopically" outside of the uterus. The ectopic endometrium, like the endometrium within the uterus, expresses estrogen receptors (ER) and progesterone receptors (PR) and undergoes hormone-dependent cell proliferation and bleeding each menstrual cycle. The goal of this study was to conduct abdominopelvic positron emission tomography (PET) scans with computed tomography (CT) imaging of rhesus macaques (Macaca mulatta) using radiotracers that target ER and PR [16α-[F]fluoroestradiol (FES) and 12-[F]fluoro-furanyl-nor-progesterone (FFNP)] in individuals with and without endometriosis.

Nonsurgical approaches to the diagnosis and evaluation of endometriosis.

An inability to make the diagnosis of endometriosis or evaluate lesion response to treatment without surgery is a clear impediment to understanding the disease and to developing new therapies. The need is particularly strong for rASRM Stage 1 or 2 disease, since higher stage (rASRM Stage 3 or 4) endometriosis can often be diagnosed by ultrasound or other imaging techniques. Despite promising findings in association studies, no biomarkers or nonsurgical diagnostic or evaluation methods for Stage 1 or Stage 2 endometriosis has yet been clinically validated.

Uterine uptake of estrogen and progestogen-based radiotracers in rhesus macaques with endometriosis.

Purpose: Few investigations have examined the uptake of radiotracers that target the prominent sex-steroid receptors in the uterus across the menstrual cycle and with disease state. We aimed to determine if uptake of the radiotracers that target estrogen and progesterone receptors (ER and PR) differ with the presence of endometriosis and/or across the menstrual cycle. We performed PET and computed tomography (CT) imaging procedures on rhesus macaques () using 16α-[18F]fluoroestradiol (FES) and 21-[18F]fluoro-furanyl-nor-progesterone (FFNP) in individuals with and without endometriosis in the proliferative and secretory phases of the menstrual cycle.

Meeting the demand for fertility services: the present and future of reproductive endocrinology and infertility in the United States.

The field of reproductive endocrinology and infertility (REI) is at a crossroads; there is a mismatch between demand for reproductive endocrinology, infertility and assisted reproductive technology (ART) services, and availability of care. This document's focus is to provide data justifying the critical need for increased provision of fertility services in the United States now and into the future, offer approaches to rectify the developing physician shortage problem, and suggest a framework for the discussion on how to meet that increase in demand. The Society of REI recommend the following: 1.

Estrogen mediates inflammatory role of mast cells in endometriosis pathophysiology.

Endometriosis is an estrogen dependent, chronic inflammatory disease characterized by the growth of endometrial lining outside of the uterus. Mast cells have emerged as key players in regulating not only allergic responses but also other mechanisms such as angiogenesis, fibrosis, and pain. The influence of estrogen on mast cell function has also been recognized as a potential factor driving disease pathophysiology in number of allergic and chronic inflammatory conditions.

The Estrogen Receptor α Cistrome in Human Endometrium and Epithelial Organoids.

Endometrial health is affected by molecular processes that underlie estrogen responses. We assessed estrogen regulation of endometrial function by integrating the estrogen receptor α (ESR1) cistromes and transcriptomes of endometrial biopsies taken from the proliferative and mid-secretory phases of the menstrual cycle together with hormonally stimulated endometrial epithelial organoids. The cycle stage-specific ESR1 binding sites were determined by chromatin immunoprecipitation and next-generation sequencing and then integrated with changes in gene expression from RNA sequencing data to infer candidate ESR1 targets in normal endometrium.

Progesterone Signaling in Endometrial Epithelial Organoids.

For pregnancy to be established, uterine cells respond to the ovarian hormones, estrogen, and progesterone, via their nuclear receptors, the estrogen receptor (ESR1) and progesterone receptor (PGR). ESR1 and PGR regulate genes by binding chromatin at genes and at distal enhancer regions, which interact via dynamic 3-dimensional chromatin structures. Endometrial epithelial cells are the initial site of embryo attachment and invasion, and thus understanding the processes that yield their receptive state is important.

Evaluation of endometrial receptivity and implantation failure.

Purpose Of Review: To succinctly review the basic mechanisms of implantation and luteal phase endometrial differentiation, the etiologies of impaired endometrial function and receptivity, and the current methods that exist to evaluate and treat impaired endometrial receptivity.

Recent Findings: Human embryo implantation requires bidirectional communication between blastocyst and a receptive endometrium. Etiologies of impaired endometrial receptivity are varied.

Defining recurrent implantation failure: a profusion of confusion or simply an illusion?

Recurrent implantation failure (RIF) is a poorly defined clinical scenario marked by failure to achieve pregnancy after multiple embryo transfers. The causes and definitions of implantation failure are heterogeneous, posing limitations on study design as well as the interpretation and application of findings. Recent studies suggest a novel, personalized approach to defining RIF.

IL-33 activates group 2 innate lymphoid cell expansion and modulates endometriosis.

Chronic inflammation and localized alterations in immune cell function are suspected to contribute to the progression of endometriosis and its associated symptoms. In particular, the alarmin IL-33 is elevated in the plasma, peritoneal fluid, and endometriotic lesions from patients with endometriosis; however, the exact role of IL-33 in the pathophysiology of endometriosis is not well understood. In this study, we demonstrate, in both humans and a murine model, that IL-33 contributes to the expansion of group 2 innate lymphoid cells (ILC2s), and this IL-33-induced ILC2 expansion modulates the endometriosis lesion microenvironment.

Role of SIRT1 and Progesterone Resistance in Normal and Abnormal Endometrium.

Context: Progesterone resistance, a known pathologic condition associated with a reduced cellular response to progesterone and heightened estrogen responses, appears to have a normal physiologic role in mammalian reproduction. The molecular mechanism responsible for progesterone resistance in normal and abnormal endometrium remains unclear.

Objective: To examine the roles of sirtuin-1 (SIRT1) in normal endometrium as well as endometrium associated with infertility and endometriosis, as an epigenetic modulator associated with progesterone resistance.

Willingness of Women with Endometriosis Planning to Undergo IVF to Participate in a Randomized Clinical Trial and the Effects of the COVID-19 Pandemic on Potential Participation.

The Pre-IVF Treatment with a GnRH Antagonist in Women with Endometriosis (PREGnant) Trial (clinicaltrials.gov no. NCT04173169) was designed to test the hypothesis that 60-day pre-treatment with an oral GnRH antagonist in women with documented endometriosis and planning an IVF cycle will result in a superior live birth rate to placebo.

Endometrial receptivity and implantation require uterine BMP signaling through an ACVR2A-SMAD1/SMAD5 axis.

During early pregnancy in the mouse, nidatory estrogen (E2) stimulates endometrial receptivity by activating a network of signaling pathways that is not yet fully characterized. Here, we report that bone morphogenetic proteins (BMPs) control endometrial receptivity via a conserved activin receptor type 2 A (ACVR2A) and SMAD1/5 signaling pathway. Mice were generated to contain single or double conditional deletion of SMAD1/5 and ACVR2A/ACVR2B receptors using progesterone receptor (PR)-cre.

Poor Endometrial Proliferation After Clomiphene is Associated With Altered Estrogen Action.

Context: Suboptimal endometrial thickening is associated with lower pregnancy rates and occurs in some infertile women treated with clomiphene.

Objective: To examine cellular and molecular differences in the endometrium of women with suboptimal vs optimal endometrial thickening following clomiphene.

Methods: Translational prospective cohort study from 2018 to 2020 at a university-affiliated clinic.

Podocalyxin is a key negative regulator of human endometrial epithelial receptivity for embryo implantation.

Study Question: How is endometrial epithelial receptivity, particularly adhesiveness, regulated at the luminal epithelial surface for embryo implantation in the human?

Summary Answer: Podocalyxin (PCX), a transmembrane protein, was identified as a key negative regulator of endometrial epithelial receptivity; specific downregulation of PCX in the luminal epithelium in the mid-secretory phase, likely mediated by progesterone, may act as a critical step in converting endometrial surface from a non-receptive to an implantation-permitting state.

What Is Known Already: The human endometrium must undergo major molecular and cellular changes to transform from a non-receptive to a receptive state to accommodate embryo implantation. However, the fundamental mechanisms governing receptivity, particularly at the luminal surface where the embryo first interacts with, are not well understood.

ARID1A and PGR proteins interact in the endometrium and reveal a positive correlation in endometriosis.

Endometriosis is a disorder in which endometrial cells normally limited to the lining of the uterus proliferate outside the uterine cavity and can cause pelvic pain and infertility. ARID1A levels are significantly reduced in the eutopic endometrium from women with endometriosis. Uterine specific Arid1a knock-out mice were infertile due to loss of epithelial progesterone receptor (PGR) signaling.