True empty follicle syndrome is a subtype of oocyte maturation abnormalities.

Objective: To review the outcomes of in vitro maturation (IVM) and in vitro fertilization (IVF) in women with empty follicle syndrome (EFS). The study evaluated the genetic underpinnings of EFS by analyzing mutations.

Materials And Methods: This retrospective case series involving 17 women with EFS over at least 2 IVF cycles was conducted.

Comparison of luteal phase and follicular phase in-vitro maturation in women with oocyte maturation abnormalities.

Research Question: Are there differences in immature oocyte retrieval following luteal phase in-vitro maturation (IVM) compared with follicular phase IVM in women with oocyte maturation abnormalities (OMAs).

Design: From January 2019 to May 2023, a retrospective cohort study at a private IVF centre included 36 women with 53 IVM cycles in Group 1 (follicular phase) and 24 women with 32 IVM cycles in Group 2 (luteal phase). Additionally, nine women had both follicular and luteal phase IVM cycles for intracycle variability analysis.

The Vagus Nerve Regulates Immunometabolic Homeostasis in the Ovine Fetus near Term: The Impact on Terminal Ileum.

Background: Glucosensing elements are widely distributed throughout the body and relay information about circulating glucose levels to the brain via the vagus nerve. However, while anatomical wiring has been established, little is known about the physiological role of the vagus nerve in glucosensing. The contribution of the vagus nerve to inflammation in the fetus is poorly understood.

Oocyte in-vitro maturation primed with letrozole-HCG versus FSH-HCG in women with oocyte maturation abnormalities: a retrospective study.

Research Question: Are there differences between in-vitro maturation (IVM) primed with letrozole-human chorionic gonadotrophin (HCG) and IVM primed with FSH-HCG in women with oocyte maturation abnormalities (OMAs), defined as at least two failed IVF cycles where immature oocytes were retrieved?

Design: This retrospective study was conducted at a private fertility clinic from January 2009 to April 2023. The final analysis included 75 women in Group 1 (IVM primed with FSH-HCG) and 52 women in Group 2 (IVM primed with letrozole-HCG).

Results: A significantly higher median number of oocytes was obtained in Group 1 compared with Group 2 {9 [interquartile range (IQR) 1-5] versus 5 (IQR 1-18); P < 0.

Factors Determining the Success of the Chronically Instrumented Non-anesthetized Fetal Sheep Model of Human Development: A Retrospective Cohort Study.

Background The chronically instrumented non-anesthetized fetal sheep (CINAFS) model has been a mainstay of human fetal development research for the past 60 years. As a large "two for one" animal model, involving the instrumentation of the ewe and her fetus, the model poses challenges to implement de novo and maintain overtime at the highest standards of operating procedures to ensure ongoing performance. A common yet conventionally underreported issue researchers face is a high rate of animal loss.

Recording and manipulation of vagus nerve electrical activity in chronically instrumented unanesthetized near term fetal sheep.

Background: The chronically instrumented pregnant sheep has been used as a model of human fetal development and responses to pathophysiologic stimuli. This is due to the unique amenability of the unanesthetized fetal sheep to the surgical placement and maintenance of catheters and electrodes, allowing repetitive blood sampling, substance injection, recording of bioelectrical activity, application of electric stimulation, and in vivo organ imaging. Recently, there has been growing interest in the pleiotropic effects of vagus nerve stimulation (VNS) on various organ systems such as innate immunity and inflammation, and metabolism.

High-resolution analyses of human sperm dynamic methylome reveal thousands of novel age-related epigenetic alterations.

Background: Children of aged fathers are at a higher risk of developing mental disorders. Alterations in sperm DNA methylation have been implicated as a potential cause. However, age-dependent modifications of the germ cells' epigenome remain poorly understood.

α7 Nicotinic Acetylcholine Receptor Signaling Modulates Ovine Fetal Brain Astrocytes Transcriptome in Response to Endotoxin.

Neuroinflammation may result in lifelong neurological disabilities. Astrocytes play a pivotal role in this process, but the mechanisms are poorly understood. No early postnatal treatment strategies exist to enhance neuroprotective potential of astrocytes.

Vagal contributions to fetal heart rate variability: an omics approach.

Objective: Fetal heart rate variability (fHRV) is an important indicator of health and disease, yet its physiological origins, neural contributions, in particular, are not well understood. We aimed to develop novel experimental and data analytical approaches to identify fHRV measures reflecting the vagus nerve contributions to fHRV.

Approach: In near-term ovine fetuses, a comprehensive set of 46 fHRV measures was computed from fetal pre-cordial electrocardiogram recorded during surgery and 72 h later without (n  =  24) and with intra-surgical bilateral cervical vagotomy (n  =  15).

Sculpting the Sculptors: Methods for Studying the Fetal Cholinergic Signaling on Systems and Cellular Scales.

The non-neuronal, immunological effects of the cholinergic signaling are exerted on the system's scale of observation via the vagus nerve and on the cellular scale via α7 nicotinic acetylcholine receptor (nAChR) signaling in myeloid cells of the periphery or brain's microglia and astrocytes. The developmental effects of such multi-scale signaling can be conceived of as an example of psychoneuroimmunological (PNI) homeokinesis and, while reported in the literature, are not yet systematically well studied. To be better understood, the intricacy of the multi-scale interactions requires relevant preclinical animal models.

Temporal Patterns in Sheep Fetal Heart Rate Variability Correlate to Systemic Cytokine Inflammatory Response: A Methodological Exploration of Monitoring Potential Using Complex Signals Bioinformatics.

Fetal inflammation is associated with increased risk for postnatal organ injuries. No means of early detection exist. We hypothesized that systemic fetal inflammation leads to distinct alterations of fetal heart rate variability (fHRV).

Can Monitoring Fetal Intestinal Inflammation Using Heart Rate Variability Analysis Signal Incipient Necrotizing Enterocolitis of the Neonate?

Objective: Necrotizing enterocolitis of the neonate is an acute inflammatory intestinal disease that can cause necrosis and sepsis. Chorioamnionitis is a risk factor of necrotizing enterocolitis. The gut represents the biggest vagus-innervated organ.

Vagus Nerve Stimulation for Treatment of Inflammation: Systematic Review of Animal Models and Clinical Studies.

Vagus nerve stimulation (VNS) has been used since 1997 for treatment of drug-resistant epilepsy. More recently, an off-label use of VNS has been explored in animal models and clinical trials for treatment of a number of conditions involving the innate immune system. The underlying premise has been the notion of the cholinergic antiinflammatory pathway (CAP), mediated by the vagus nerves.

Instrumentation of Near-term Fetal Sheep for Multivariate Chronic Non-anesthetized Recordings.

The chronically instrumented pregnant sheep has been used as a model of human fetal development and responses to pathophysiologic stimuli such as endotoxins, bacteria, umbilical cord occlusions, hypoxia and various pharmacological treatments. The life-saving clinical practices of glucocorticoid treatment in fetuses at risk of premature birth and the therapeutic hypothermia have been developed in this model. This is due to the unique amenability of the non-anesthetized fetal sheep to the surgical placement and maintenance of catheters and electrodes, allowing repetitive blood sampling, substance injection, recording of bioelectrical activity, application of electric stimulation and in vivo organ imaging.

Fetal microglial phenotype in vitro carries memory of prior in vivo exposure to inflammation.

Objective: Neuroinflammation in utero may result in life-long neurological disabilities. The molecular mechanisms whereby microglia contribute to this response remain incompletely understood.

Methods: Lipopolysaccharide (LPS) or saline were administered intravenously to non-anesthetized chronically instrumented near-term fetal sheep to model fetal inflammation in vivo.

Does heart rate variability reflect the systemic inflammatory response in a fetal sheep model of lipopolysaccharide-induced sepsis?

Fetal inflammatory response occurs during chorioamnionitis, a frequent and often subclinical inflammation associated with increased risk for brain injury and life-lasting neurologic deficits. No means of early detection exist. We hypothesized that systemic fetal inflammation without septic shock will be reflected in alterations of fetal heart rate (FHR) variability (fHRV) distinguishing baseline versus inflammatory response states.

Effect of maternal ketoacidosis on the ovine fetus.

Ketoacidosis during pregnancy carries significant risk of intrauterine fetal demise, but little is known about the impact of ketoacids on the ovine fetus. We report a case series of maternal ketoacidosis in ewes. Maternal ketoacidosis may result in biochemical and acid-base fetal abnormalities associated with changes in feto-placental unit perfusion.

Adaptive shut-down of EEG activity predicts critical acidemia in the near-term ovine fetus.

In fetal sheep, the electrocorticogram (ECOG) recorded directly from the cortex during repetitive heart rate (FHR) decelerations induced by umbilical cord occlusions (UCO) predictably correlates with worsening hypoxic-acidemia. In human fetal monitoring during labor, the equivalent electroencephalogram (EEG) can be recorded noninvasively from the scalp. We tested the hypothesis that combined fetal EEG - FHR monitoring allows for early detection of worsening hypoxic-acidemia similar to that shown for ECOG-FHR monitoring.

The Ovine Fetal and Placental Inflammatory Response to Umbilical Cord Occlusions With Worsening Acidosis.

We hypothesized that repetitive umbilical cord occlusions (UCOs) leading to severe acidemia will stimulate a placental and thereby fetal inflammatory response which will be exacerbated by chronic hypoxemia and low-grade bacterial infection. Chronically instrumented fetal sheep served as controls or underwent repetitive UCOs for up to 4 hours or until fetal arterial pH was <7.00.

Cell fate regulation by gelsolin in human gynecologic cancers.

Chemoresistance is a major hurdle in cancer treatment. Down-regulation of apoptosis pathways is one of the key determinants for chemoresistance. Here, we report higher gelsolin (GSN) levels in chemoresistant gynecological cancer cells compared with their sensitive counterparts.

Expression of the growth factor progranulin in endothelial cells influences growth and development of blood vessels: a novel mouse model.

Progranulin is a secreted glycoprotein that regulates cell proliferation, migration and survival. It has roles in development, tumorigenesis, wound healing, neurodegeneration and inflammation. Endothelia in tumors, wounds and placenta express elevated levels of progranulin.

Chemerin suppresses ovarian follicular development and its potential involvement in follicular arrest in rats treated chronically with dihydrotestosterone.

In the present study, we have investigated the cellular mechanisms of androgen-induced antral follicular growth arrest and the possible involvement of chemerin and its receptor chemokine-like receptor 1 (CMKLR1) in this process, using a chronically androgenized rat model. We hypothesize that hyperandrogenism induces antral follicle growth arrest via the action of chemerin and ovarian structural changes, resulting from granulosa cell and oocyte apoptosis and theca cell survival. Dihydrotestosterone (DHT) treatment resulted in increased expression of chemerin and CMKLR1 in antral follicles, absence of corpus luteum, and increased atypical follicles.

Altered expression of miRNAs in a dihydrotestosterone-induced rat PCOS model.

Background: The polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine condition characterized by hyperandrogenism, hyperinsulinemia, insulin resistance and chronic anovulation. Regulation and interaction of a multitude of genes required for follicular development are found to be altered in PCOS. MicroRNAs (miRNAs) mediate posttranscriptional gene regulation by binding to the 3´ untranslated region of mRNAs to either inhibit or enhance translation.

Mural granulosa cell gene expression associated with oocyte developmental competence.

Background: Ovarian follicle development is a complex process. Paracrine interactions between somatic and germ cells are critical for normal follicular development and oocyte maturation. Studies have suggested that the health and function of the granulosa and cumulus cells may be reflective of the health status of the enclosed oocyte.

Transporter-mediated multidrug resistance and its modulation by Chinese medicines and other herbal products.

The main cause of failure in cancer drug therapy is the emergence of cellular resistance to drugs. Cancer cells, after exposure to one drug, can become simultaneously insensitive to mechanistically and chemically unrelated drugs, a phenotype known as multidrug resistance (MDR). Although a number of mechanisms have been proposed to mediate MDR, the classical cellular mechanism involves the overexpression of several members of the ATP-binding cassette (ABC) superfamily of transporters, leading to increased efflux and decreased intracellular drug accumulation.