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Frontiers in Medicine 2024Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare autosomal dominant inheritable disease caused by Fumarate hydratase (FH) gene germline mutation. It is...
BACKGROUND
Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare autosomal dominant inheritable disease caused by Fumarate hydratase (FH) gene germline mutation. It is speculated that for HRLCC infertility women with multiple uterine leiomyomas, preimplantation genetic testing may help block transmission of mutated FH gene during pregnancy.
CASE PRESENTATION
We present the case of a 26-year-old nulligravida with a history of early-onset uterine leiomyomatosis had a heterozygous nonsense mutation [NM_000143.4 (FH): c.1027C > T(p.Arg343Ter)] in the HRLLC gene. After ovulation induction and fertilization, preimplantation genetic testing for monogenic disorders (PGT-M) on embryos revealed the absence of the pathogenic allele in two blastomeres. Uterine fibroids were identified before embryo transfer, leading to a submucosal myomectomy and long period of pituitary suppression by Gonadotropin-releasing hormone analog (GnRHa). The patient achieved a healthy live birth after the second cycle of frozen-thawed embryo transfer.
CONCLUSION
This case details the successful treatment of an infertile patient with an HRLLC family history, resulting in a healthy birth through myomectomy and PGT-M selected embryo transplantation. Our literature search indicates the first reported live birth after HRLLC-PGT-M.
PubMed: 38933105
DOI: 10.3389/fmed.2024.1400694 -
Nutrients Jun 2024Androgen production primarily occurs in Leydig cells located in the interstitial compartment of the testis. In aging males, testosterone is crucial for maintaining... (Review)
Review
Androgen production primarily occurs in Leydig cells located in the interstitial compartment of the testis. In aging males, testosterone is crucial for maintaining muscle mass and strength, bone density, sexual function, metabolic health, energy levels, cognitive function, as well as overall well-being. As men age, testosterone production by Leydig cells of the testes begins to decline at a rate of approximately 1% per year starting from their 30s. This review highlights recent findings concerning the use of natural polyphenolics compounds, such as flavonoids, resveratrol, and phenolic acids, to enhance testosterone production, thereby preventing age-related degenerative conditions associated with testosterone insufficiency. Interestingly, most of the natural polyphenolic antioxidants having beneficial effects on testosterone production tend to enhance the expression of the steroidogenic acute regulatory protein () gene in Leydig cells. The STAR protein facilitates the entry of the steroid precursor cholesterol inside mitochondria, a rate-limiting step for androgen biosynthesis. Natural polyphenolic compounds can also improve the activities of steroidogenic enzymes, hypothalamus-pituitary gland axis signaling, and testosterone bioavailability. Thus, many polyphenolic compounds such as luteolin, quercetin, resveratrol, ferulic acid phenethyl ester or gigantol may be promising in delaying the initiation of late-onset hypogonadism accompanying aging in males.
Topics: Male; Humans; Hypogonadism; Antioxidants; Polyphenols; Testosterone; Leydig Cells; Animals; Aging; Phosphoproteins; Resveratrol
PubMed: 38931170
DOI: 10.3390/nu16121815 -
Children (Basel, Switzerland) Jun 2024Misophonia is a neurophysiological disorder with behavioral implications, is complex and multifactorial in origin, and is characterized by an atypical and... (Review)
Review
Misophonia is a neurophysiological disorder with behavioral implications, is complex and multifactorial in origin, and is characterized by an atypical and disproportionate emotional response to specific sounds or associated visual stimuli. Triggers include human-generated sounds, mainly sounds related to feeding and breathing processes, and repetitive mechanical sounds. In response to the triggering stimulus, the patient experiences immediate, high-intensity, disproportionate physical and emotional reactions that affect their quality of life and social functioning. The symptoms of misophonia can occur at any age, but onset in childhood or adolescence is most common. Affected children live in a constant state of anxiety, suffer continuous physical and emotional discomfort, and are thus exposed to significant chronic stress. Chronic stress, especially during childhood, has consequences on the main biological systems through the dysregulation of the hypothalamic-pituitary-adrenal axis, including the gastrointestinal tract. Here, we provide arguments for a positive correlation between misophonic pathology and gastrointestinal symptoms, and this hypothesis may be the starting point for further longitudinal studies that could investigate the correlations between these childhood vulnerabilities caused by misophonia and their effect on the gastrointestinal system. Further research to study this hypothesis is essential to ensure correct and timely diagnosis and optimal psychological and pharmacological support.
PubMed: 38929278
DOI: 10.3390/children11060699 -
Antioxidants (Basel, Switzerland) Jun 2024Psychosis, defined as a set of symptoms that results in a distorted sense of reality, is observed in several psychiatric disorders in addition to schizophrenia. This... (Review)
Review
Psychosis, defined as a set of symptoms that results in a distorted sense of reality, is observed in several psychiatric disorders in addition to schizophrenia. This paper reviews the literature relevant to the underlying neurobiology of psychosis. The dopamine hypothesis has been a major influence in the study of the neurochemistry of psychosis and in development of antipsychotic drugs. However, it became clear early on that other factors must be involved in the dysfunction involved in psychosis. In the current review, it is reported how several of these factors, namely dysregulation of neurotransmitters [dopamine, serotonin, glutamate, and γ-aminobutyric acid (GABA)], neuroinflammation, glia (microglia, astrocytes, and oligodendrocytes), the hypothalamic-pituitary-adrenal axis, the gut microbiome, oxidative stress, and mitochondrial dysfunction contribute to psychosis and interact with one another. Research on psychosis has increased knowledge of the complexity of psychotic disorders. Potential new pharmacotherapies, including combinations of drugs (with pre- and probiotics in some cases) affecting several of the factors mentioned above, have been suggested. Similarly, several putative biomarkers, particularly those related to the immune system, have been proposed. Future research on both pharmacotherapy and biomarkers will require better-designed studies conducted on an all stages of psychotic disorders and must consider confounders such as sex differences and comorbidity.
PubMed: 38929148
DOI: 10.3390/antiox13060709 -
Brain Sciences May 2024Depression is the most common mental disorder worldwide. Both antidepressants and psychotherapy are effective in treating depression, but the response to these... (Review)
Review
Depression is the most common mental disorder worldwide. Both antidepressants and psychotherapy are effective in treating depression, but the response to these treatments is often incomplete. Yoga-based interventions (YBIs) have been advocated by some researchers as a promising form of alternative treatment for depression. Recent research has attempted to identify the biological mechanisms associated with the antidepressant actions of YBIs. In this scoping review, conducted according to the PRISMA-ScR guidelines, the PubMed and Scopus databases were searched to retrieve research on biomarkers of response to YBIs in patients with depression. These studies were also critically reviewed to evaluate their methodological quality and any sources of bias. Nineteen studies were included in the review. Based on these studies, there is preliminary evidence that YBIs may be associated with increased serum brain-derived neurotrophic factor (BDNF) and reduced serum cortisol and interleukin-6 (IL-6) in patients with depression. However, many of these changes were also observed in the control arms, and the overall quality of the research was low. At present, it cannot be concluded that there are reliable biomarkers of response to YBIs in depression, though there are some potential biological correlates. Further advances in this field will depend critically on improvements in study design, particularly the minimization of sources of bias and the selection of more specific and sensitive biomarkers based on existing evidence from other treatment modalities.
PubMed: 38928543
DOI: 10.3390/brainsci14060543 -
International Journal of Molecular... Jun 2024The physiology of reproduction has been of interest to researchers for centuries. The purpose of this work is to review the development of our knowledge on the... (Review)
Review
The physiology of reproduction has been of interest to researchers for centuries. The purpose of this work is to review the development of our knowledge on the neuroendocrine background of the regulation of ovulation. We first describe the development of the pituitary gland, the structure of the median eminence (ME), the connection between the hypothalamus and the pituitary gland, the ovarian and pituitary hormones involved in ovulation, and the pituitary cell composition. We recall the pioneer physiological and morphological investigations that drove development forward. The description of the supraoptic-paraventricular magnocellular and tuberoinfundibular parvocellular systems and recognizing the role of the hypophysiotropic area were major milestones in understanding the anatomical and physiological basis of reproduction. The discovery of releasing and inhibiting hormones, the significance of pulse and surge generators, the pulsatile secretion of the gonadotropin-releasing hormone (GnRH), and the subsequent pulsatility of luteinizing (LH) and follicle-stimulating hormones (FSH) in the human reproductive physiology were truly transformative. The roles of three critical neuropeptides, kisspeptin (KP), neurokinin B (NKB), and dynorphin (Dy), were also identified. This review also touches on the endocrine background of human infertility and assisted fertilization.
Topics: Humans; Ovulation; Female; Neurosecretory Systems; Animals; Pituitary Gland; Kisspeptins; Neurokinin B; Luteinizing Hormone; Gonadotropin-Releasing Hormone; Dynorphins; Hypothalamus
PubMed: 38928237
DOI: 10.3390/ijms25126531 -
Cancers Jun 2024The prediction of the regrowth potential of pituitary adenomas after surgery is challenging. The genome-wide DNA methylation profiling of pituitary adenomas may separate...
BACKGROUND
The prediction of the regrowth potential of pituitary adenomas after surgery is challenging. The genome-wide DNA methylation profiling of pituitary adenomas may separate adenomas into distinct methylation classes corresponding to histology-based subtypes. Specific genes and differentially methylated probes involving regrowth have been proposed, but no study has linked this epigenetic variance with regrowth potential and the clinical heterogeneity of nonfunctioning pituitary adenomas. This study aimed to investigate whether DNA methylation profiling can be useful as a clinical prognostic marker.
METHODS
A DNA methylation analysis by Illumina's MethylationEPIC array was performed on 54 pituitary macroadenomas from patients who underwent transsphenoidal surgery during 2007-2017. Twelve patients were excluded due to an incomplete postoperative follow-up, degenerated biobank-stored tissue, or low DNA methylation quality. For the quantitative measurement of the tumor regrowth rate, we conducted a 3D volumetric analysis of tumor remnant volume via annual magnetic resonance imaging. A linear mixed effects model was used to examine whether different DNA methylation clusters had different regrowth patterns.
RESULTS
The DNA methylation profiling of 42 tissue samples showed robust DNA methylation clusters, comparable with previous findings. The subgroup of 33 nonfunctioning pituitary adenomas of an SF1-lineage showed five subclusters with an approximately unbiased score of 86%. There were no overall statistically significant differences when comparing hazard ratios for regrowth of 100%, 50%, or 0%. Despite this, plots of correlated survival estimates suggested higher regrowth rates for some clusters. The mixed effects model of accumulated regrowth similarly showed tendencies toward an association between specific DNA methylation clusters and regrowth potential.
CONCLUSION
The DNA methylation profiling of nonfunctioning pituitary adenomas may potentially identify adenomas with increased growth and recurrence potential. Larger validation studies are needed to confirm the findings from this explorative pilot study.
PubMed: 38927917
DOI: 10.3390/cancers16122210 -
Genes Jun 2024Previous studies have demonstrated the essential role of the Kisspeptin/Neurokinin B/Dynorphin A (KNDy) pathway in female reproductive biology by regulating the activity...
Previous studies have demonstrated the essential role of the Kisspeptin/Neurokinin B/Dynorphin A (KNDy) pathway in female reproductive biology by regulating the activity of the hypothalamic-pituitary-gonadal axis. Identified loss-of-function mutations in these genes are linked to various reproductive disorders. This study investigated genetic disorders linked to mutations in the genes related to premature ovarian insufficiency (POI). A cohort of 14 Mexican POI patients underwent genetic screening using PCR-SSCP and Sanger sequencing, assessing the genetic variations' impact on protein function thereafter using multiple in silico tools. The PCR excluded extensive deletions, insertions, and duplications, while SSCP detected five genetic variants. Variations occurred in the (c.58G>A and c.242C>G), (c.1091A>T), (c.600C>T), and (c.36G>T) genes, whereas no genetic anomalies were found in genes. Each single-nucleotide variant underwent genotyping using PCR-SSCP in 100 POI-free subjects. Their allelic frequencies paralleled the patient group. These observations indicate that allelic variations in the genes may not contribute to POI etiology. Hence, screening for mutations in genes should not be a part of the diagnostic protocol for POI.
Topics: Humans; Female; Primary Ovarian Insufficiency; Mexico; Adult; Neurokinin B; Kisspeptins; Cohort Studies; Polymorphism, Single Nucleotide; Receptors, Kisspeptin-1; Enkephalins; Protein Precursors
PubMed: 38927724
DOI: 10.3390/genes15060788 -
Genes Jun 2024is a LIM-homeodomain transcription factor that affects body size in mammals by regulating the secretion of pituitary hormones. Akita, Shiba Inu, and Mame Shiba Inu dogs...
is a LIM-homeodomain transcription factor that affects body size in mammals by regulating the secretion of pituitary hormones. Akita, Shiba Inu, and Mame Shiba Inu dogs are Japanese native dog breeds that have different body sizes. To determine whether plays a role in the differing body sizes of these three dog breeds, we sequenced the gene in the three breeds, which led to the identification of an SNP in codon 280 (S280N) associated with body size. The allele frequency at this SNP differed significantly between the large Akita and the two kinds of smaller Shiba dogs. To validate the function of this SNP on body size, we introduced this change into the gene of mice. Homozygous mutant mice (S279N) were found to have significantly increased body lengths and weights compared to heterozygous mutant (S279N) and wild-type (S279N) mice several weeks after weaning. These results demonstrate that a nonsynonymous substitution in plays an important role in regulating body size in mammals.
Topics: Animals; LIM-Homeodomain Proteins; Transcription Factors; Mice; Body Size; Dogs; Polymorphism, Single Nucleotide; Gene Frequency; Male; Female
PubMed: 38927675
DOI: 10.3390/genes15060739 -
Biomedicines Jun 2024Research has identified fetal risk factors for adult diseases, forming the basis for the Developmental Origins of Health and Disease (DOHaD) hypothesis. DOHaD suggests... (Review)
Review
A Review of Fetal Development in Pregnancies with Maternal Type 2 Diabetes Mellitus (T2DM)-Associated Hypothalamic-Pituitary-Adrenal (HPA) Axis Dysregulation: Possible Links to Pregestational Prediabetes.
Research has identified fetal risk factors for adult diseases, forming the basis for the Developmental Origins of Health and Disease (DOHaD) hypothesis. DOHaD suggests that maternal insults during pregnancy cause structural and functional changes in fetal organs, increasing the risk of chronic diseases like type 2 diabetes mellitus (T2DM) in adulthood. It is proposed that altered maternal physiology, such as increased glucocorticoid (GC) levels associated with a dysregulated hypothalamic-pituitary-adrenal (HPA) axis in maternal stress and T2DM during pregnancy, exposes the fetus to excess GC. Prenatal glucocorticoid exposure reduces fetal growth and programs the fetal HPA axis, permanently altering its activity into adulthood. This programmed HPA axis is linked to increased risks of hypertension, cardiovascular diseases, and mental disorders in adulthood. With the global rise in T2DM, particularly among young adults of reproductive age, it is crucial to prevent its onset. T2DM is often preceded by a prediabetic state, a condition that does not show any symptoms, causing many to unknowingly progress to T2DM. Studying prediabetes is essential, as it is a reversible stage that may help prevent T2DM-related pregnancy complications. The existing literature focuses on HPA axis dysregulation in T2DM pregnancies and its link to fetal programming. However, the effects of prediabetes on HPA axis function, specifically glucocorticoid in pregnancy and fetal outcomes, are not well understood. This review consolidates research on T2DM during pregnancy, its impact on fetal programming via the HPA axis, and possible links with pregestational prediabetes.
PubMed: 38927579
DOI: 10.3390/biomedicines12061372