Human DNA topoisomerase I poisoning causes R loop-mediated genome instability attenuated by transcription factor IIS.

DNA topoisomerase I can contribute to cancer genome instability. During catalytic activity, topoisomerase I forms a transient intermediate, topoisomerase I-DNA cleavage complex (Top1cc) to allow strand rotation and duplex relaxation, which can lead to elevated levels of DNA-RNA hybrids and micronuclei. To comprehend the underlying mechanisms, we have integrated genomic data of Top1cc-triggered hybrids and DNA double-strand breaks (DSBs) shortly after Top1cc induction, revealing that Top1ccs increase hybrid levels with different mechanisms.

The impact of ovarian stimulation on the human endometrial microenvironment.

Study Question: How does ovarian stimulation (OS), which is used to mature multiple oocytes for ART procedures, impact the principal cellular compartments and transcriptome of the human endometrium in the periovulatory and mid-secretory phases?

Summary Answer: During the mid-secretory window of implantation, OS alters the abundance of endometrial immune cells, whereas during the periovulatory period, OS substantially changes the endometrial transcriptome and impacts both endometrial glandular and immune cells.

What Is Known Already: Pregnancies conceived in an OS cycle are at risk of complications reflective of abnormal placentation and placental function. OS can alter endometrial gene expression and immune cell populations.

Mechanisms of endometrial aging: lessons from natural conceptions and assisted reproductive technology cycles.

Until recently, the study of age-related decline in fertility has focused primarily on the ovary; depletion of the finite pool of oocytes and increases in meiotic errors leading to oocyte aneuploidy are well-established mechanisms by which fertility declines with advancing age. Comparatively little is known about the impact of age on endometrial function. The endometrium is a complex tissue comprised of many cell types, including epithelial, stromal, vascular, immune and stem cells.

Impaired receptivity of thin endometrium: therapeutic potential of mesenchymal stem cells.

The endometrium is a resilient and highly dynamic tissue, undergoing cyclic renewal in preparation for embryo implantation. Cyclic endometrial regeneration depends on the intact function of several cell types, including parenchymal, endothelial, and immune cells, as well as adult stem cells that can arise from endometrial or extrauterine sources. The ability of the endometrium to undergo rapid, repeated regeneration without scarring is unique to this tissue.

Mesenchymal stem cell secretome alters gene expression and upregulates motility of human endometrial stromal cells.

In Brief: Endometrial stromal cell motility is fundamental to regeneration and repair of this tissue and crucial for successful reproduction. This paper shows a role for the mesenchymal stem cell (MSC) secretome in enhancing endometrial stromal cell motility.

Abstract: Cyclic regeneration and repair of the endometrium are crucial for successful reproduction.

Expression of down-regulated ERV LTR elements associates with immune activation in human small-cell lung cancers.

Small-cell lung cancer (SCLC) is an aggressive cancer characterized by immunosuppressive features leading to poor responses to current immunotherapies. Activation of transposable elements (TE) can trigger an innate immune response, which can synergize with immunotherapeutic protocols in patients. However, TE activity in relation to immune gene response is not fully known in human SCLC.

Endocrine disruptors and female fertility: a review of pesticide and plasticizer effects.

An ongoing interest in environmental exposures and female fertility has led to an increasing number of studies focusing on endocrine-disrupting chemicals (EDCs). Both natural and synthetic compounds have the ability to impact reproductive health by altering the structure and/or function of genes and proteins that facilitate normal ovarian and endometrial functions. This mini-review aims to summarize the effects of some of the most common EDCs on female fertility, including the effects of pesticides and plasticizer alternatives (phthalates, bisphenol A), based on available data in human studies.

Expression of glucocorticoid and androgen receptors in bone marrow-derived hematopoietic and nonhematopoietic murine endometrial cells.

Objective: To determine whether bone marrow (BM)-derived cells engrafting the murine endometrium express the glucocorticoid receptor (GR) and androgen receptor (AR). Recent data demonstrate that BM is a long-term source of multiple hematopoietic and nonhematopoietic endometrial cell types. Important roles for glucocorticoids and androgens in regulating endometrial functions, including decidualization and early embryo attachment/invasion, have very recently emerged.

Towards an Improved Understanding of the Effects of Elevated Progesterone Levels on Human Endometrial Receptivity and Oocyte/Embryo Quality during Assisted Reproductive Technologies.

Ovarian stimulation is an indispensable part of IVF and is employed to produce multiple ovarian follicles. In women who undergo ovarian stimulation with gonadotropins, supraphysiological levels of estradiol, as well as a premature rise in progesterone levels, can be seen on the day of hCG administration. These alterations in hormone levels are associated with reduced embryo implantation and pregnancy rates in IVF cycles with a fresh embryo transfer.

Bone Marrow-Derived Cells in Endometrial Cancer Pathogenesis: Insights from Breast Cancer.

Endometrial cancer is the most common gynecological cancer, representing 3.5% of all new cancer cases in the United States. Abnormal stem cell-like cells, referred to as cancer stem cells (CSCs), reside in the endometrium and possess the capacity to self-renew and differentiate into cancer progenitors, leading to tumor progression.

Mouse Cre drivers: tools for studying disorders of the human female neuroendocrine-reproductive axis†.

Benign disorders of the human female reproductive system, such primary ovarian insufficiency and polycystic ovary syndrome are associated with infertility and recurrent miscarriage, as well as increased risk of adverse health outcomes, including cardiovascular disease and type 2 diabetes. For many of these conditions, the contributing molecular and cellular processes are poorly understood. The overarching similarities between mice and humans have rendered mouse models irreplaceable in understanding normal physiology and elucidating pathological processes that underlie disorders of the female reproductive system.

The incidence of ectopic/heterotopic pregnancies after blastocyst-stage frozen-thawed embryo transfers compared with that after cleavage-stage: a Society for Assisted Reproductive Technologies Clinical Outcomes Reporting System study.

Objective: To investigate whether there is a difference in the ectopic/heterotopic pregnancy rate of blastocyst-stage frozen-thawed embryo transfers (FETs) compared with that of cleavage-stage FETs.

Design: A retrospective cohort study.

Setting: Not applicable.

Increased male live-birth rates after blastocyst-stage frozen-thawed embryo transfers compared with cleavage-stage frozen-thawed embryo transfers: a SART registry study.

Objective: To investigate whether there is a difference in live-birth gender rates in blastocyst-stage frozen-thawed embryo transfers (FETs) compared with those in cleavage-stage FETs.

Design: Retrospective cohort study.

Setting: Academic medical center.

Hematological Humanization of Immune-Deficient Mice.

Mice with human hematopoietic system have become critical for research and preclinical studies. Mice with patient-derived xenografts of different tumors exist without human immune system. Answers can be addressed with the same immunodeficient mice that are chimeric for the human hemato-lymphoid system (humanized mice).

Dynamic Expression of Interleukin-33 and ST2 in the Mouse Reproductive Tract Is Influenced by Superovulation.

Interleukin-33 (IL-33) is an IL-1 family cytokine with pleiotropic effects on diverse cell types. Dysregulated IL-33 signaling has been implicated in pregnancy-related disorders, including preeclampsia and recurrent pregnancy loss, and in ovarian function in women undergoing controlled ovarian stimulation for in vitro fertilization. To date, expression of IL-33 and its receptor subunit, ST2, in the female reproductive tract remains poorly characterized.

Comparison of 2-Hour Oral Glucose Tolerance Test and Hemoglobin A1C in the Identification of Pre-Diabetes in Women with Infertility and Recurrent Pregnancy Loss.

Research Question: Does hemoglobin A1C (HbA1C) predict pre-diabetes (pre-DM) in a population of women with infertility and/or recurrent pregnancy loss (RPL), when considering the 75 g, 2-hour oral glucose tolerance test (2h GTT) as the gold standard?

Design: Retrospective study of 242 patients with infertility or RPL presenting to a university-affiliated reproductive endocrinology and infertility clinic between January 2012 and December 2016 who underwent screening for disorders of glucose metabolism with a 2h GTT. The prevalence of pre-DM as defined by HbA1C 5.7% to 6.

Ongoing barriers to immediate postpartum long-acting reversible contraception: a physician survey.

Background: Postpartum women are at risk for unintended pregnancy. Access to immediate long-acting reversible contraception (LARC) may help decrease this risk, but it is unclear how many providers in the United States routinely offer this to their patients and what obstacles they face. Our primary objective was to determine the proportion of United States obstetric providers that offer immediate postpartum LARC to their obstetric patients.

The role of mesenchymal-epithelial transition in endometrial function.

Background: The human uterine endometrium undergoes significant remodeling and regeneration on a rapid and repeated basis, after parturition, menstruation, and in some cases, injury. The ability of the adult endometrium to undergo cyclic regeneration and differentiation/decidualization is essential for successful human reproduction. Multiple key physiologic functions of the endometrium require the cells of this tissue to transition between mesenchymal and epithelial phenotypes, processes known as mesenchymal-epithelial transition (MET) and epithelial-mesenchymal transition (EMT).

Improved outcomes after blastocyst-stage frozen-thawed embryo transfers compared with cleavage stage: a Society for Assisted Reproductive Technologies Clinical Outcomes Reporting System study.

Objective: To investigate whether there is a difference in obstetrical and perinatal outcomes in blastocyst frozen-thawed embryo transfers (FETs) compared with cleavage-stage FET.

Design: A retrospective cohort study.

Setting: Not applicable.

Metabolic screening in patients with polycystic ovary syndrome is largely underutilized among obstetrician-gynecologists.

Women with polycystic ovary syndrome have substantially higher rates of insulin resistance, impaired glucose tolerance, type 2 diabetes, dyslipidemia, and metabolic syndrome when compared with women without the disease. Given the high prevalence of these comorbidities, guidelines issued by the American College of Obstetricians and Gynecologists and the Endocrine Society recommend that all women with polycystic ovary syndrome undergo screening for impaired glucose tolerance and dyslipidemia with a 2 hour 75 g oral glucose tolerance test and fasting lipid profile upon diagnosis and also undergo repeat screening every 2-5 years and every 2 years, respectively. Although a hemoglobin A1C and/or fasting glucose are widely used screening tests for diabetes, both the American College of Obstetricians and Gynecologists and the Endocrine Society preferentially recommend the 2 hour oral glucose tolerance test in women with polycystic ovary syndrome as a superior indicator of impaired glucose tolerance/diabetes mellitus.

Role of Medical Management for Uterine Leiomyomas.

Uterine leiomyomas, or fibroids, are the most common benign tumor in reproductive aged women. Affected women may remain asymptomatic or may report symptoms related to abnormal uterine bleeding, infertility, or pelvic pain and pressure. Depending on a patient's symptomatology and reproductive plans, treatment options include expectant management, medical management (hormonal and non-hormonal), or surgical management (myomectomy or hysterectomy).

Reporting in vitro fertilization cycles to the Society for Assisted Reproductive Technology database: where have all the cycles gone?

Objective: To assess the relationship between live birth rates (LBRs) and the incidence of under-reported cycles by IVF clinics.

Design: Cohort study.

Setting: Not applicable.

Myometrial artery calcifications and aging.

Objective: This study aims to determine whether myometrial artery calcifications increase with age and whether uterine sections are an appropriate model for studying vascular aging.

Methods: An observational study of 172 women (aged 45 y or older) who underwent hysterectomy for benign indications at the University Hospital (Newark, NJ) between July 1, 2009 and June 1, 2012 was performed. Women with a history of malignancy, undocumented last menstrual period, or unavailable uterine tissue slides were excluded.