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Cancers Jun 2024We aimed to report sexual and reproductive outcomes following post-chemotherapy robot-assisted retroperitoneal unilateral lymph node dissection (PC-rRPLND) for...
We aimed to report sexual and reproductive outcomes following post-chemotherapy robot-assisted retroperitoneal unilateral lymph node dissection (PC-rRPLND) for non-seminomatous germ cell tumors (NSGCTs) at a high-volume cancer center. We collected records regarding sexual and reproductive outcomes of patients undergoing unilateral PC-rRPLND for stage II NSGCTs from January 2018 to November 2021. Preoperative and postoperative (at 12 months) ejaculatory function as well as erectile function, based on the International Index of Erectile Function-5 (IIEF-5) and Erection Hardness Score (EHS), were assessed. Only patients with a pre-operative IIEF-5 of ≥22 and EHS of ≥3 were included in this analysis. Overall, 22 patients undergoing unilateral PC-rRPLND met the inclusion criteria. Of these, seven (31.8%) patients presented an andrological disorder of any type after PC-rRPLND. Specifically, retrograde ejaculation was present in three (13.6%) patients and hypospermia was present in one (4.5%) patient. Moreover, three (13.6%) patients yielded erectile dysfunction (IIEF-5 < 22 and/or EHS < 3). Lastly, two (9.1%) succeeded in naturally conceiving a child after PC-rRPLND. Retrograde ejaculation is confirmed to be one of the most common complications of PC-rRPLND. Moreover, a non-negligible number of patients experience erectile dysfunction.
PubMed: 38927936
DOI: 10.3390/cancers16122231 -
Biology Jun 2024(1) Background: The recent emphasis on sexual and gender diversity's impact on human health underscores the need for tailored diagnostic and therapeutic approaches in... (Review)
Review
(1) Background: The recent emphasis on sexual and gender diversity's impact on human health underscores the need for tailored diagnostic and therapeutic approaches in neurology. The aim of this article is to conduct a narrative review of the available scientific literature on sex differences in cerebrospinal fluid analysis. (2) Methods: The literature search encompassed PubMed databases, focusing on cerebrospinal fluid analysis and sex differences, considering parameters like cerebrospinal fluid protein content, cell count, albumin quotient (QAlb) and intrathecal IgG synthesis. (3) Results: Nine articles from the past two decades were identified, revealing limited research in this area. Males consistently exhibited higher cerebrospinal fluid protein content and albumin quotient values across various pathologies and age groups. Consequently, males more frequently manifested blood-cerebrospinal fluid barrier dysfunction than females. No significant sex differences were observed in cerebrospinal fluid leukocyte count or intrathecal IgG synthesis. (4) Conclusions: This review highlights the dearth of research on sex differences in cerebrospinal fluid analysis, despite consistent findings of higher protein content and albumin quotient values in males. Revisiting current diagnostic thresholds based on sex is crucial for accurate prognosis and personalised treatment strategies in neurological disorders. Moving towards sex-specific approaches in clinical practice is imperative for advancing personalised medicine.
PubMed: 38927300
DOI: 10.3390/biology13060420 -
Molecular Metabolism Jun 2024Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality, and its incidence is increasing due to endemic obesity. HCC is sexually dimorphic in both...
OBJECTIVE
Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality, and its incidence is increasing due to endemic obesity. HCC is sexually dimorphic in both humans and rodents with higher incidence in males, although the mechanisms contributing to these correlations remain unclear. Here, we examined the role of sphingosine kinase 2 (SphK2), the enzyme that regulates the balance of bioactive sphingolipid metabolites, sphingosine-1-phosphate (S1P) and ceramide, in gender specific MASH-driven HCC.
METHODS
Male and female mice were fed a high fat diet with sugar water, a clinically relevant model that recapitulates MASH-driven HCC in humans followed by physiological, biochemical cellular and molecular analyses. In addition, correlations with increased risk of HCC recurrence were determined in patients.
RESULTS
Here, we report that deletion of SphK2 protects both male and female mice from Western diet-induced weight gain and metabolic dysfunction without affecting hepatic lipid accumulation or fibrosis. However, SphK2 deficiency decreases chronic diet-induced hepatocyte proliferation in males but increases it in females. Remarkably, SphK2 deficiency reverses the sexual dimorphism of HCC, as SphK2 male mice are protected whereas the females develop liver cancer. Only in male mice, chronic western diet induced accumulation of the autophagy receptor p62 and its downstream mediators, the antioxidant response target NQO1, and the oncogene c-Myc. SphK2 deletion repressed these known drivers of HCC development. Moreover, high p62 expression correlates with poor survival in male HCC patients but not in females. In hepatocytes, lipotoxicity-induced p62 accumulation is regulated by sex hormones and prevented by SphK2 deletion. Importantly, high SphK2 expression in male but not female HCC patients is associated with a more aggressive HCC differentiation status and increased risk of cancer recurrence.
CONCLUSIONS
This work identifies SphK2 as a potential regulator of HCC sexual dimorphism and suggests SphK2 inhibitors now in clinical trials could have opposing, gender-specific effects in patients.
PubMed: 38925249
DOI: 10.1016/j.molmet.2024.101971 -
Cells Jun 2024gene loss-of-function mutation leads to Primary Ciliary Dyskinesia (PCD), a disease caused by motile cilia dysfunction. Previously, we demonstrated that knockout of the...
gene loss-of-function mutation leads to Primary Ciliary Dyskinesia (PCD), a disease caused by motile cilia dysfunction. Previously, we demonstrated that knockout of the gene in mice replicates several features of PCD, such as hydrocephalus, defects in left-right body symmetry, and male infertility, with a complete absence of sperm in the reproductive tract. The majority of knockout animals die before sexual maturation due to severe hydrocephalus and failure to thrive, which precludes fertility studies. Here, we performed the expression analysis of the gene during gonad development and in adult testes. We showed that starts its expression during the first wave of spermatogenesis, specifically at the meiotic stage, and that its expression is restricted to the germ cells in the adult testes, suggesting that plays a role in spermatozoa formation. Subsequently, we conditionally deleted the gene in adult males and demonstrated that even partial ablation of the gene leads to asthenoteratozoospermia with multiple morphological abnormalities of sperm flagella (MMAF) in mice. The analysis of the seminiferous tubules in -deficient mice revealed defects in spermatogenesis with accumulation of seminiferous tubules at the spermiogenesis and spermiation phases. Furthermore, analysis of fertility in heterozygous knockout mice revealed a reduction in sperm count and motility as well as abnormal sperm morphology. Additionally, males exhibited a shorter fertile lifespan. Overall, these results suggest the important role of and gene dosage in male fertility. These findings may have an impact on the genetic and fertility counseling practice of PCD patients carrying loss-of-function mutations.
Topics: Animals; Male; Spermatogenesis; Fertility; Mice; Spermatozoa; Mice, Knockout; Testis; Infertility, Male; Mice, Inbred C57BL
PubMed: 38920681
DOI: 10.3390/cells13121053 -
Diseases (Basel, Switzerland) May 2024This comparative cross-sectional study conducted at the "Pius Brinzeu" healthcare center in Timisoara explored the differential impacts of pregnancy planning status on...
This comparative cross-sectional study conducted at the "Pius Brinzeu" healthcare center in Timisoara explored the differential impacts of pregnancy planning status on sexual function, body image, and relationship satisfaction among pregnant women. Employing the Female Sexual Function Index (FSFI), Body Esteem Scale for Adolescents and Adults (BESAQ), and the Beck Depression Inventory (BDI-II), the study analyzed responses from 107 participants divided into groups of planned ( = 59, mean age 28.5 ± 5.2) and unplanned ( = 48, mean age 27.3 ± 4.8) pregnancies. In the first trimester, unplanned pregnancies reported higher median scores in desire (4.7 vs. 3.6, = 0.005), arousal (4.5 vs. 3.8, = 0.001), and lubrication (4.6 vs. 3.7, = 0.015) compared to planned pregnancies. Satisfaction scores also favored unplanned pregnancies in the first trimester (4.8 vs. 3.9, = 0.009). Similar trends were observed in subsequent trimesters, with unplanned pregnancies consistently reporting higher FSFI scores, indicating a robust sexual function. Risk factors significantly associated with sexual dysfunction were a higher BMI in the first trimester (beta coefficient: -0.124, = 0.019), unmarried civil status (beta coefficient: -0.323, = 0.045), history of previous abortion (beta coefficient: -0.451, = 0.012), irregular menstrual cycles (beta coefficient: -0.384, = 0.026), and rural living area (beta coefficient: -0.278, = 0.034). Notably, unplanned pregnancy itself was not a significant risk factor for sexual dysfunction (beta coefficient: -0.054, = 0.095). Regarding relationship dynamics, planned pregnancies exhibited significantly higher satisfaction with partner support (4.1 ± 0.9 vs. 3.7 ± 1.1, = 0.041) and communication within the couple (4.0 ± 1.0 vs. 3.5 ± 1.2, = 0.020), whereas unplanned pregnancies reported higher satisfaction with emotional closeness (4.3 ± 0.7 vs. 3.8 ± 1.0, = 0.004). Concerns about managing professional activities and household chores were significantly more prevalent in the unplanned pregnancy group (62.50% vs. 33.90%, = 0.014). Unplanned pregnancies demonstrated better initial sexual function but faced greater challenges in relationship satisfaction and managing pregnancy demands. Identifying and addressing the risk factors associated with sexual dysfunction can provide targeted interventions to improve the well-being of pregnant women, regardless of pregnancy planning status.
PubMed: 38920541
DOI: 10.3390/diseases12060109 -
Frontiers in Public Health 2024As cancer survival rates increase, it has become crucial to pay attention to the long-term quality of life of survivors, including sexual functioning. The quality of...
INTRODUCTION
As cancer survival rates increase, it has become crucial to pay attention to the long-term quality of life of survivors, including sexual functioning. The quality of sexual life and fear of cancer progression are often unmet needs, significantly impacting cancer patients' overall quality of life. In this study, we investigate these factors in Romanian female cancer patients and highlight their relationship with mental health and demographic variables.
METHODS
This study included 242 Romanian female cancer patients who completed questionnaires assessing sexual functioning (EORTC QLQ-SHQ22), fear of cancer progression (FoP-Q), depression (PHQ-9), and anxiety (GAD-7). We examined these relationships using descriptive, exploratory, and regression analyses.
RESULTS
Around 50% of patients reported impairments in sexual satisfaction and pain during sex. Lower sexual satisfaction increased sexual dysfunction, and heightened fear of cancer progression (FCP) were associated with depression, anxiety, younger age, lower education, rural residence, and unmarried status.
DISCUSSION
This study reveals a complex interplay between sexual health, fear of cancer progression, and psychological well-being among female cancer survivors in Romania. Addressing sexual concerns, providing psychoeducation, promoting coping with the fear of progression, and utilizing interdisciplinary interventions are essential to improving these patients' overall quality of life. These findings underscore the need for integrated care approaches that consider both physical and psychological dimensions of cancer survivorship.
Topics: Humans; Female; Romania; Quality of Life; Middle Aged; Surveys and Questionnaires; Adult; Fear; Neoplasms; Anxiety; Aged; Disease Progression; Depression; Cancer Survivors; Sexual Behavior
PubMed: 38919914
DOI: 10.3389/fpubh.2024.1417681 -
Frontiers in Plant Science 2024(Sieb. et Zucc.) Maxim. (ESM) which accumulates several principal flavonoid compounds including epimedin A, B, C and icariin, is extensively utilized in traditional...
(Sieb. et Zucc.) Maxim. (ESM) which accumulates several principal flavonoid compounds including epimedin A, B, C and icariin, is extensively utilized in traditional herbs for sexual dysfunction, osteoporosis etc. In China, ESM has a wealth of wild plant resources and characterized by significant variability in medicinal compounds accumulation. Understanding the diversity of ESMs can lead to better utilization of these plant resources. In this study, we integrated the metabolomic and transcriptomic analysis of three ESMs that originated in Anhui, Hubei and Jiangxi in China. Results showed that the flavonoid biosynthesis as well as the related gene expression in these ESMs revealed substantial differences. For example, the epimedin A, B, C and icariin as well as some related gene expression in ESMs from Anhui are significantly lower than those of in others. These results suggested that the ESMs from wild population without quality checkout may not be suitable for directly use as the materials for preparation of Chinese medicine and ESMs with different accumulation of metabolites could be used for distinct applications.
PubMed: 38919822
DOI: 10.3389/fpls.2024.1424956 -
Frontiers in Endocrinology 2024Gender incongruence (GI) is characterized by a marked incongruence between an individual's experienced/expressed gender and the assigned sex at birth. It includes strong...
INTRODUCTION
Gender incongruence (GI) is characterized by a marked incongruence between an individual's experienced/expressed gender and the assigned sex at birth. It includes strong displeasure about his or her sexual anatomy and secondary sex characteristics. In some people, this condition produces a strong distress with anxiety and depression named gender dysphoria (GD). This condition appears to be associated with genetic, epigenetics, hormonal as well as social factors. Given that L-glutamate is the major excitatory neurotransmitter in the central nervous system, also associated with male sexual behavior as well as depression, we aimed to determine whether metabotropic glutamate receptors are involved in GD.
METHODS
We analyzed 74 single nucleotide polymorphisms located at the metabotropic glutamate receptors (mGluR1, mGluR3, mGluR4, mGluR5, mGluR7 and mGluR8) in 94 transgender 94 cisgender people. The allele and genotype frequencies were analyzed by c2 test contrasting male and female cisgender and transgender populations. The strength of the associations was measured by binary logistic regression, estimating the odds ratio (OR) for each genotype. Measurement of linkage disequilibrium, and subsequent measurement of haplotype frequencies were also performed considering three levels of significance: P ≤ 0.05, P ≤ 0.005 and P ≤ 0.0005. Furthermore, false positives were controlled with the Bonferroni correction (P ≤ 0.05/74 = 0.00067).
RESULTS
After analysis of allele and genotypic frequencies, we found twenty-five polymorphisms with significant differences at level P ≤ 0.05, five at P ≤ 0.005 and two at P ≤ 0.0005. Furthermore, the only two polymorphisms (rs9838094 and rs1818033) that passed the Bonferroni correction were both related to the metabotropic glutamate receptor 7 (mGluR7) and showed significant differences for multiple patterns of inheritance. Moreover, the haplotype T/G [OR=0.34 (0.19-0.62); P<0.0004] had a lower representation in the transgender population than in the cisgender population, with no evidence of sex cross-interaction.
CONCLUSION
We provide genetic evidence that the mGluR7, and therefore glutamatergic neurotransmission, may be involved in GI and GD.
Topics: Humans; Male; Receptors, Metabotropic Glutamate; Female; Polymorphism, Single Nucleotide; Adult; Transgender Persons; Gender Dysphoria; Genotype; Young Adult; Middle Aged; Linkage Disequilibrium
PubMed: 38919484
DOI: 10.3389/fendo.2024.1382861 -
Reproductive Biology and Endocrinology... Jun 2024Erectile dysfunction (ED) is a common male sexual dysfunction, with an increasing incidence, and the current treatment is often ineffective.
BACKGROUND
Erectile dysfunction (ED) is a common male sexual dysfunction, with an increasing incidence, and the current treatment is often ineffective.
METHODS
Vascular endothelial growth factor (VEGFA) was used to treat bone marrow-derived mesenchymal stem cells (BM-MSCs), and their cell migration rates were determined by Transwell assays. The expression of the von Willebrand Factor (vWF)VE-cadherin, and endothelial nitric oxide synthase(eNOS) endothelial markers was determined by qRT‒PCR and Western blot analyses. The MALAT1-induced differentiation of BM-MCs to ECs via the CDC42/PAK1/paxillin pathway was explored by transfecting VEGFA-induced BM-MSC with si-MALAT1 and overexpressing CDC42 and PAK1. The binding capacity between CDC42, PAK1, and paxillin in VEGFA-treated and non-VEGFA-treated BM-MSCs was examined by protein immunoprecipitation. MiR-206 was overexpressed in VEGFA-induced BM-MSC, and the binding sites of MALAT1, miR-206, and CDC42 were identified using a luciferase assay. Sixty male Sprague‒Dawley rats were divided into six groups (n = 10/group). DMED modelling was demonstrated by APO experiments and was assessed by measuring blood glucose levels. Erectile function was assessed by measuring the intracavernosa pressure (ICP) and mean arterial pressure (MAP). Penile erectile tissue was analysed by qRT‒PCR, Western blot analysis, and immunohistochemical staining.
RESULTS
MALAT1 under VEGFA treatment conditions regulates the differentiation of BM-MSCs into ECs by modulating the CDC42/PAK1/paxillin axis. In vitro experiments demonstrated that interference with CDC42 and MALAT1 expression inhibited the differentiation of BM-MSCs to ECs. CDC42 binds to PAK1, and PAK1 binds to paxillin. In addition, CDC42 in the VEGFA group had a greater ability to bind to PAK1, whereas PAK1 in the VEGFA group had a greater ability to bind to paxillin. Overexpression of miR-206 in VEGFA-induced BM-MSCs demonstrated that MALAT1 competes with the CDC42 3'-UTR for binding to miR-206, which in turn is involved in the differentiation of BM-MSCs to ECs. Compared to the DMED model group, the ICP/MAP ratio was significantly greater in the three BM-MSCs treatment groups.
CONCLUSIONS
MALAT1 facilitates BM-MSC differentiation into ECs by regulating the miR-206/CDC42/PAK1/paxillin axis to improve ED. The present findings revealed the vital role of MALAT1 in the repair of BM-MSCs for erectile function and provided new mechanistic insights into the BM-MSC-mediated repair of DMED.
Topics: Male; Animals; RNA, Long Noncoding; MicroRNAs; Cell Differentiation; cdc42 GTP-Binding Protein; Rats, Sprague-Dawley; Signal Transduction; Rats; p21-Activated Kinases; Mesenchymal Stem Cells; Erectile Dysfunction; Paxillin; Endothelial Cells; Cells, Cultured; Vascular Endothelial Growth Factor A
PubMed: 38918809
DOI: 10.1186/s12958-024-01240-8 -
Gynecological Endocrinology : the... Dec 2024Female sexual interest and arousal disorder (FSIAD) is the most prevalent female sexual dysfunction in the postmenopause. (Review)
Review
INTRODUCTION
Female sexual interest and arousal disorder (FSIAD) is the most prevalent female sexual dysfunction in the postmenopause.
OBJECTIVE
The aim of this review is to provide a summary of the currently available evidence on the use of testosterone in the treatment of FSIAD in postmenopausal women.
METHODS
A narrative review on the topic was performed. Only randomized controlled trials (RCTs) and systematic reviews and meta-analysis were considered. 123 articles were screened, 105 of them assessed for eligibility, and finally 9 were included in qualitative synthesis following the PRISMA declaration.
RESULTS
Current evidence recommends, with moderate therapeutic benefit, the use of systemic transdermal testosterone within the premenopausal physiological range in postmenopausal women with Hypoactive Sexual Desire Disorder (HSDD), the previous entity for low desire dysfunction, not primarily related to modifiable factors or comorbidities such as relationship or mental health problems. The available evidence is based on studies with heterogeneity on their design (different testosterone doses, routes of administration, testosterone use in combination and alone, sexual instruments of measurement). There is no data indicating severe short-term adverse effects, although long-term safety data is lacking.
CONCLUSIONS
Despite having testosterone as a valuable tool, therapeutic strategies are lacking in the pharmacological field of HSDD/FSIAD. Neuroimaging studies could provide valuable information regarding the sexual desire substrate and suggest the potential application of already approved drugs for women with a good safety profile. The use of validated instruments for HSDD in postmenopausal women, considering the level of distress, is necessary to be able to draw robust conclusions on the evaluated treatments.
Topics: Humans; Female; Testosterone; Sexual Dysfunctions, Psychological; Postmenopause; Libido
PubMed: 38913119
DOI: 10.1080/09513590.2024.2364220