Hypoxic conditions affect transcriptome of endometrial stromal cells in endometriosis and promote TGFBI axis.

Background: Endometriosis is characterized by the ectopic growth of endometrial-like cells, causing chronic pelvic pain, adhesions and impaired fertility in women of reproductive age. Usually, these lesions grow in the peritoneal cavity in a hypoxic environment. Hypoxia is known to affect gene expression and protein kinase (PK) activity.

Genomic Effects of Biomechanical Loading in Adolescent Human Growth Plate Cartilage: A Pilot Study.

Objective: The genomic effects of biomechanical loading on human growth plate cartilage are unknown so far. To address this, we used rare human growth plate biopsies obtained from children undergoing epiphysiodesis and exposed them to precisely controlled mechanical loading using a microloading device. The biopsies were cultured 24 hours after mechanical loading, followed by RNA-sequencing analyses to decipher the genomic regulation.

miR-193b-5p and miR-374b-5p Are Aberrantly Expressed in Endometriosis and Suppress Endometrial Cell Migration In Vitro.

(1) Background: Endometriosis is a highly prevalent gynecological disease affecting 10% of women of reproductive age worldwide. miRNAs may play a role in endometriosis, though their exact function remains unclear. This study aimed to identify differentially expressed miRNAs in endometriosis and study their functions in the disease.

Transcriptomic profiling of the oocyte-cumulus-granulosa cell complex from estrogen receptor β knockout mice.

Objective: To study the role of estrogen receptor β in follicle development and maturation and the response to gonadotropin stimulation aiming at superovulation.

Design: Experimental study and transcriptomic analysis.

Setting: Karolinka Institutet, medical university.

Transcriptomic Profile of Breast Tissue of Premenopausal Women Following Treatment with Progesterone Receptor Modulator: Secondary Outcomes of a Randomized Controlled Trial.

Progesterone receptor antagonism is gaining attention due to progesterone's recognized role as a major mitogen in breast tissue. Limited but promising data suggest the potential efficacy of antiprogestins in breast cancer prevention. The present study presents secondary outcomes from a randomized controlled trial and examines changes in breast mRNA expression following mifepristone treatment in healthy premenopausal women.

Global Transcriptomic Analysis of Placentas from Women with Gestational SARS-CoV-2 Infection during the Third Trimester of Pregnancy.

The COVID-19 pandemic has had a significant and enduring influence on global health, including maternal and fetal well-being. Evidence suggests that placental dysfunction is a potential consequence of SARS-CoV-2 infection during pregnancy, which may result in adverse outcomes such as preeclampsia and preterm birth. However, the molecular mechanisms underlying this association remain unclear, and it is uncertain whether a mature placenta can protect the fetus from SARS-CoV-2 infection.

Antiprogestins reduce epigenetic field cancerization in breast tissue of young healthy women.

Background: Breast cancer is a leading cause of death in premenopausal women. Progesterone drives expansion of luminal progenitor cells, leading to the development of poor-prognostic breast cancers. However, it is not known if antagonising progesterone can prevent breast cancers in humans.

Uterine fluid microRNAs are dysregulated in women with recurrent implantation failure.

Study Question: Is the composition of microRNAs (miRNAs) in uterine fluid (UF) of women with recurrent implantation failure (RIF) different from that of healthy fertile women?

Summary Answer: The composition of miRNAs in UF of women with RIF is different from that of healthy fertile women and the dysregulated miRNAs are associated with impaired endometrial receptivity and embryo implantation.

What Is Known Already: It has previously been demonstrated that the miRNAs secreted from endometrial cells into the UF contribute to the achievement of endometrial receptivity. Endometrial miRNAs are dysregulated in women with RIF.

Trophoblast derived extracellular vesicles specifically alter the transcriptome of endometrial cells and may constitute a critical component of embryo-maternal communication.

Background: The period of time when the embryo and the endometrium undergo significant morphological alterations to facilitate a successful implantation-known as "window of implantation"-is a critical moment in human reproduction. Embryo and the endometrium communicate extensively during this period, and lipid bilayer bound nanoscale extracellular vesicles (EVs) are purported to be integral to this communication.

Methods: To investigate the nature of the EV-mediated embryo-maternal communication, we have supplemented trophoblast analogue spheroid (JAr) derived EVs to an endometrial analogue (RL 95-2) cell layer and characterized the transcriptomic alterations using RNA sequencing.

Stromal Heterogeneity in the Human Proliferative Endometrium-A Single-Cell RNA Sequencing Study.

The endometrium undergoes regular regeneration and stromal proliferation as part of the normal menstrual cycle. To better understand cellular interactions driving the mechanisms in endometrial regeneration we employed single-cell RNA sequencing. Endometrial biopsies were obtained during the proliferative phase of the menstrual cycle from healthy fertile women and processed to single-cell suspensions which were submitted for sequencing.

Syndecan-1 modulates the invasive potential of endometrioma via TGF-β signalling in a subgroup of women with endometriosis.

Study Question: What is the physiological role of transforming growth factor-beta (TGF-β1) and syndecans (SDC1, SDC4) in endometriotic cells in women with endometriosis?

Summary Answer: We observed an abnormal, pro-invasive phenotype in a subgroup of samples with ovarian endometriosis, which was reversed by combining gene silencing of SDC1 with the TGF-β1 treatment.

What Is Known Already: Women with endometriosis express high levels of TGF-β1 and the proteoglycan co-receptors SDC1 and SDC4 within endometriotic cysts. However, how SDC1 and SDC4 expression is regulated by TGF-β1 and the physiological significance of the high expression in endometriotic cysts remains unknown as does the potential role in disease severity.

Compartmentalized gene expression profiling of receptive endometrium reveals progesterone regulated ENPP3 is differentially expressed and secreted in glycosylated form.

The complexity of endometrial receptivity at the molecular level needs to be explored in detail to improve the management of infertility. Here, differential expression of transcriptomes in receptive endometrial glands and stroma revealed Ectonucleotide Pyrophosphatase/Phosphodiesterase 3 (ENPP3) as a progesterone regulated factor and confirmed by various methods, both at mRNA and protein level. The involvement of ENPP3 in embryo attachment was tested in an in vitro model for human embryo implantation.

Recent advances in understanding endometrial receptivity: molecular basis and clinical applications.

Advancement in the field of ART has lead to the possibility of achieving good quality embryos. However, the success rate in ART needs further improvement. This is largely dependent on identifying the receptive endometrium for the successful implantation of embryos as well as modulating the endometrium to the receptive stage.

Polyethylene glycated leukemia inhibitory factor antagonist inhibits human blastocyst implantation and triggers apoptosis by down-regulating embryonic AKT.

Objective: To study the effect of polyethylene glycated leukemia inhibitory factor (LIF) antagonist (PEGLA) in the human blastocyst viability and implantation process.

Design: In vitro study.

Setting: University hospital and research laboratory.