Normal Females Research Articles

Value of miR200b and its combination with other biochemical markers in the diagnosis of epithelial ovarian cancer.

This study aimed to analyse the diagnostic performance of miR200b in epithelial ovarian cancer (EOC) in a group of Egyptian patients and to evaluate the combined use of miR200b with other biomarkers as a reliable diagnostic and prognostic indicator of EOC. We tested the expression of cell-free miR200b in 30 EOC patients before undergoing optimum cytoreductive surgery, 19 females with benign ovarian disease and 14 normal healthy females using quantitative real time PCR. All cases were tested for CA125, HE4 and CRP. The results were compared between the three groups. The double combination of miR200b with each biomarker was tested for a possible improvement of the diagnostic power of the test. MiR200b was significantly overexpressed in EOC patients compared to the other groups, we determined 1.88 folds as the best cutoff for miR200b expression to discriminate between EOC and non-malignant cases with a sensitivity of 63.3% and a specificity of 71%. CA125, HE4 and CRP were evaluated and showed a sensitivity of 96.7%, 45.5%, 81.8% respectively and a specificity of 75.9%, 66.7% and 90% respectively. We evaluated the combined use of miR200b with each biomarker, the best results were seen with the combined use of miR200b and CA125. We concluded that the combined use of miR200b and CA125 could serve as a reliable tool in the initial diagnosis of EOC, and a predictor of event free survival of the disease.

The function of HgLac in Heterodera glycines and its potential as a control target

The soybean cyst nematode (SCN; Heterodera glycines) is one of the most devastating pathogens for soybean production. The second stage juvenile (J2) invades the host root, develops and form white females which then become brown cysts enter the soil. The brown cyst wall plays a key role in protecting inside eggs from adverse environmental conditions. However, the function of cyst wall tanning (sclerotization and pigmentation) in nematodes is not clear. A browning-related gene discovered from the whole-genome sequencing was cloned and characterized in this study, the gene was confirmed to be the laccase gene and was named HgLac. HgLac mRNA and HgLac protein was detected in the epidermis of juveniles using in situ hybridization and immunolocalization techniques. The HgLac expression level was greater in fourth-stage juveniles (J4s) than in the other stages. Knockdown of HgLac by in vitro RNA interference (RNAi) significantly decreased the infectivity, development and reproduction of J2s but had no effect on cyst wall tanning. Further research revealed that HgLac expression in nematodes was significantly suppressed by 35.41–59.17 % through in planta RNAi, 52.96–58.19 % females could not tan successfully, and the female wall was very soft and fragile, with a low egg hatching rate (1.33 %), which was significantly lower than that of normal females (68.85 %). These results indicate that HgLac plays a key role in cyst wall tanning and suppressing the development and reproduction of the SCN, which provides new ideas for the use of this gene as a target to control SCN.

Prevalence of Human Pegivirus Infection during High Risk Pregnancy and its Vertical Transmission to the Newborn

Human Pegivirus (HPgV-1), which was known as hepatitis G virus (HGV) or GB virus C (GBV-C) is a single – stranded positive RNA virus belonging to the genus Pegivirus of Flaviviridae family. Its genomic organization is similar to that of HCV with which it has only 25% homology at the nucleotide level. The aim of this study is to evaluate the prevalence of HPgV-1 among high risk pregnant women (with HCV infection or history of previous blood transfusion) and normal pregnant women. In addition to detect the vertical transmission of the virus to their newborns. Thirty term high risk and thirty term normal pregnant females were screened for HPgV-1 RNA using the reverse transcription PCR technique. HPgV-1 was detected in six females among those who have HCV infection (33.3%) and in two females among recipients of blood transfusion (16.6%), also it was detected in one female of the control group (3.3%). The outcome of newborns showed three newborns with HPgV-1 infection out of six born to the females who have both HCV and HPgV-1 infection and one newborn of the infected mother of the control group, however, liver functions of the newborns were in the normal range for age requiring long term follow up.

Pupil to limbus diameter ratio as an emerging autonomic function test and its correlation with anthropometric parameters in different phases of menstrual cycle

The menstrual cycle is a physiological change in normal females, indicating the proper functioning of both endocrine and reproductive health. The pupil to limbus diameter (PLD) ratio is defined as the ratio of pupil diameter measured at an axial plane to the limbus diameter measured at the same or a parallel axial plane. Alterations in estrogen and progesterone levels may influence cardiac autonomic functions. This study aimed to correlate the PLD ratio with anthropometric parameters, such as body mass index (BMI) and waist circumference (WC), during different phases of the menstrual cycle among medical students.Methods: A cross-sectional study was conducted among first- and second-year female MBBS students aged 17 to 22 years. Anthropometric parameters, including height, weight, BMI, and WC, were measured for all participants. Eye photographs were taken during the follicular and luteal phases of the menstrual cycle, and the diameters were measured manually using the two-box method. The PLD ratios for both eyes showed a significant positive correlation with BMI (right eye: r = 0.682, p < 0.000; left eye: r = 0.430, p < 0.000) and waist circumference (right eye: r = 0.456, p < 0.000; left eye: r = 0.315, p < 0.001). The PLD ratio can serve as a simple, non-invasive, and cost-effective autonomic function test.

Current landscape of fertility induction in males with congenital hypogonadotropic hypogonadism.

Congenital hypogonadotropic hypogonadism (CHH) is a rare reproductive disorder caused by deficient secretion or action of gonadotropin-releasing hormone (GnRH) and is a hormonally treatable form of male infertility. Both pulsatile GnRH treatment and combined gonadotropin therapy effectively induce spermatogenesis in 75%-80% of males with CHH, albeit the ejaculate does not usually approach normal semen parameters by WHO criteria. This is in some contrast to the cumulative fertility outcomes in females with CHH on gonadotropin treatment that are indistinguishable from those of reproductively normal females. Emerging data provide insights into early life determinants of male fertility (i.e., minipuberty), and research has identified key predictors of outcomes for fertility-inducing treatment in men with CHH. Such developments provide mounting evidence for tailoring approaches to maximize fertility potential in CHH, although there is no clear consensus to date on the optimal approach to fertility-inducing treatment. This review provides an up-to-date review on the current evidence underpinning therapeutic approaches for inducing spermatogenesis in males with CHH. In the absence of evidence-based clinical guidelines, this synthesis of current evidence provides guidance for clinicians working with males with CHH seeking fertility.

Transcriptome analysis of four types of gonadal tissues in largemouth bass (Micropterus salmoides) to reveal its sex-related genes.

The sex determination system of largemouth bass (Micropterus salmoides, LMB) is XX/XY; however, the underlying molecular mechanisms involved in early sex differentiation, gonadal development, and exogenous hormone-induced sex reversal remain unknown. In this study, LMB at 15days post-hatching (dph) were fed diets containing 20mg/kg of 17α-methyltestosterone (17α-MT) or 30mg/kg of 17β-estradiol (17β-E2) for 60days, respectively. Serum steroid levels, histological observations of the gonads, and identification of sex-specific markers were employed to screen the gonads of 60-day-old normal female fish (XX-F), normal male fish (XY-M), 17β-E2 induced pseudo-female fish (XY-F), and 17α-MT-induced pseudo-male fish (XX-M) for transcriptome sequencing in order to uncover genes and pathway involved in the process of sexual reversal. The results from histology and serum sex steroid hormone analysis showed that both 17α-MT and 17β-E2 were capable of inducing sex reversal of LMB at 15dph. Transcriptome results revealed a total of 2,753 genes exhibiting differential expression, and the expression pattern of these genes in the gonads of XX-M or XY-F resembled that of normal females or males. The male sex-biased genes that are upregulated in XX-M and downregulated in XY-F are referred to as key genes for male reversal, while the female sex-biased genes that are upregulated in XY-F and downregulated in XX-M are referred to as key genes for female reversal. Finally, 12 differentially expressed genes (DEGs) related to male sex reversal were screened, including star2, cyp17a, cyp11b1, dmrt1, amh, sox9a, katnal1, spata4, spata6l, spata7, spata18 and foxl3. 2 DEGs (foxl2a and cyp19a1b) were found to be associated with female sex reversal. The changes in these genes collectively influence the direction of sex differentiation of LMB. Among them, star2, dmrt1 and cyp19a1b with significantly altered expression levels may play potentially crucial role in the process of gender reversal. The expression patterns of 21 randomly selected genes were verified using qRT-PCR which confirmed the reliability and accuracy of the RNA-seq results. These findings not only enhance our understanding of the molecular basis underlying sex reversal but also provide crucial data support for future breeding research on unisexual LMB.

Identification of Fingerprint Pattern and Lip Print Pattern in Females of Type 2 Diabetes Mellitus as a Biomarker

Diabetes mellitus (D.M.) is a chronic metabolic disorder that has increased worldwide. Fingerprints and lip prints are noninvasive procedures that are genetically used in criminal cases and to determine genetic disorders such as Diabetes mellitus type 2. Dermatoglyphics is the epidermal ridge configuration, the ridged skin on our fingertips, palms, and toes. There are three types (Whorl, et al.). Cheiloscopy, derived from the Greek word (cheilos), which means lip, is the study of crinkles and grooves that are perceptible on our lips and unique. We conducted our research with 90 females, 45 were with (DMT2), and 45 were normal females over 30 years old. The samples were collected in different Kurdistan regions (Erbil City, Qaladza Town, Koya Town, and Koya University). We collected all 10 (ten) fingerprint patterns and divided them into Whorl, loop, and arch using an ink pad. Also, lip samples were collected by using lipstick on A4 paper. According to our research, the predominant fingerprints and lip prints in females with type 2 diabetes were loops for both hands (right (31.1%) and left (28.4%)), and for lips, the print was intersected grooves (28.9%). The predominant fingerprint and lip print for normal females were also loops in both hands (right (28%) and left (25%)), and the lip print was complete vertical grooves (42.2%). The study showed no association between fingerprint pattern and diabetes mellitus type 2 and cannot be used as a biomarker for it. However, there is a clear association between lip print pattern and diabetes mellitus type 2, and it can be used as a specific biomarker.

Novel Drp1 GTPase Inhibitor, Drpitor1a: Efficacy in Pulmonary Hypertension.

Drp1 (dynamin-related protein 1), a large GTPase, mediates the increased mitochondrial fission, which contributes to hyperproliferation of pulmonary artery smooth muscle cells in pulmonary arterial hypertension (PAH). We developed a potent Drp1 GTPase inhibitor, Drpitor1a, but its specificity, pharmacokinetics, and efficacy in PAH are unknown. Drpitor1a's ability to inhibit recombinant and endogenous Drp1 GTPase was assessed. Drpitor1a's effects on fission were studied in control and PAH human pulmonary artery smooth muscle cells (hPASMC) and blood outgrowth endothelial cells (BOEC). Cell proliferation and apoptosis were studied in hPASMC. Pharmacokinetics and tissue concentrations were measured following intravenous and oral drug administration. Drpitor1a's efficacy in regressing monocrotaline-PAH was assessed in rats. In a pilot study, Drpitor1a reduced PA remodeling only in females. Subsequently, we compared Drpitor1a to vehicles in control and monocrotaline-PAH females. Drp1 GTPase activity was increased in PAH hPASMC. Drpitor1a inhibited the GTPase activity of recombinant and endogenous Drp1 and reversed the increased fission, seen in PAH hPASMC and PAH BOEC. Drpitor1a inhibited proliferation and induced apoptosis in PAH hPASMC without affecting electron transport chain activity, respiration, fission/fusion mediator expression, or mitochondrial Drp1 translocation. Drpitor1a did not inhibit proliferation or alter mitochondrial dynamics in normal hPASMC. Drpitor1a regressed monocrotaline-PAH without systemic vascular effects or toxicity. Drpitor1a is a specific Drp1 GTPase inhibitor that reduces mitochondrial fission in PAH hPASMC and PAH BOEC. Drpitor1a reduces proliferation and induces apoptosis in PAH hPASMC and regresses monocrotaline-PAH. Drp1 is a therapeutic target in PAH, and Drpitor1a is a potential therapy with an interesting therapeutic sexual dimorphism.

Hybridization between Aedes aegypti and Aedes mascarensis mosquitoes leads to disruption of male sex determination

Understanding the sex determination pathway and its disruptions in mosquitoes is critical for the effective control of disease vectors through genetic manipulations based on sex separation. When male hybrids of Aedes aegypti females and Ae. mascarensis males are backcrossed to Ae. aegypti females, a portion of the backcross progeny manifests as males with abnormal sexual differentiation. We discovered a significant correlation between pupal abnormalities and the feminization of subsequent adults exemplified by the relative abundance of ovarian and testicular tissues. All intersex individuals were genetic males as they expressed a male determining factor, Nix. Further, our analysis of the sex-specific splicing of doublesex and fruitless transcripts demonstrated the presence of both male and female splice variants indicating that sex determination is disrupted. A comparative transcriptomic analysis revealed similar expression levels of most female-associated genes in reproductive organs and carcasses between intersexual males and normal females. Moreover, intersexes had largely normal gene expression in testes but significant gene downregulation in male accessory glands when compared with normal males. We conclude that evolving hybrid incompatibilities between Ae. aegypti and Ae. mascarensis involve disruption of sex determination and are accompanied by changes in gene expression associated with sexual differentiation.

Preconceptional paternal caloric restriction of high-fat diet-induced obesity in Wistar rats dysregulates the metabolism of their offspring via AMPK/SIRT1 pathway

BackgroundObesity is a metabolic syndrome where allelic and environmental variations together determine the susceptibility of an individual to the disease. Caloric restriction (CR) is a nutritional dietary strategy recognized to be beneficial as a weight loss regime in obese individuals. Preconceptional parental CR is proven to have detrimental effects on the health and development of their offspring. As yet studies on maternal CR effect on their offspring are well established but paternal CR studies are not progressing. In current study, the impact of different paternal CR regimes in diet-induced obese male Wistar rats (WNIN), on their offspring concerning metabolic syndrome are addressed.MethodsHigh-fat diet-induced obese male Wistar rats were subjected to caloric restriction of 50% (HFCR-I) and 40% (HFCR-II) and then they were mated with normal females. The male parent’s reproductive function was assessed by sperm parameters and their DNMT’s mRNA expression levels were also examined. The offspring’s metabolic function was assessed by physiological, biochemical and molecular parameters.ResultsThe HFCR-I male parents have shown reduced body weights, compromised male fertility and reduced DNA methylation activity. Further, the HFCR-I offspring showed attenuation of the AMPK/SIRT1 pathway, which is associated with the progression of proinflammatory status and oxidative stress. In line, the HFCR-I offspring also developed altered glucose and lipid homeostasis by exhibiting impaired glucose tolerance & insulin sensitivity, dyslipidemia and steatosis. However, these effects were largely mitigated in HFCR-II offspring. Regarding the obesogenic effects, female offspring exhibited greater susceptibility than male offspring, suggesting that females are more prone to the influences of the paternal diet.ConclusionThe findings highlight that HFCR-I resulted in paternal undernutrition, impacting the health of offspring, whereas HFCR-II largely restored the effects of a high-fat diet on their offspring. As a result, moderate caloric restriction has emerged as an effective weight loss strategy with minimal implications on future generations. This underscores the shared responsibility of fathers in contributing to sperm-specific epigenetic imprints that influence the health of adult offspring.

5 mC modification of steroid hormone biosynthesis-related genes orchestrates feminization of channel catfish induced by high-temperature

To elucidate the mechanism behind channel catfish feminization induced by high temperature, gonad samples were collected from XY pseudo-females and wild-type females and subjected to high-throughput sequencing for Whole-Genome-Bisulfite-Seq (WGBS) and transcriptome sequencing (RNA-Seq). The analysis revealed 50 differentially methylated genes between wild-type females and XY pseudo-females, identified through the analysis of KEGG pathways and GO enrichment in the promoter of the genome and differentially methylated regions (DMRs). Among these genes, multiple differential methylation sites observed within the srd5a2 gene. Repeatability tests confirmed 7 differential methylation sites in the srd5a2 gene in XY pseudo-females compared to normal males, with 1 specific differential methylation site (16608174) distinguishing XY pseudo-females from normal females. Interestingly, the expression of these genes in the transcriptome showed no difference between wild-type females and XY pseudo-females. Our study concluded that methylation of the srd5a2 gene sequence leads to decreased expression, which inhibits testosterone synthesis while promoting the synthesis of 17β-estradiol from testosterone. This underscores the significance of the srd5a2 gene in the sexual differentiation of channel catfish, as indicated by the ipu00140 KEGG pathway analysis.

Molecular detection of human papillomavirus prevalence in clinically normal females and identification of high-risk HPV 16 and 18 under low resources setting: a cohort study from Sri Lanka.

The online version contains supplementary material available at 10.1007/s13337-024-00875-w.

Left ventricular wall thickening predicts left atrial low voltage areas in patients undergoing catheter ablation for atrial fibrillation

Abstract Background The success rate of circumferential pulmonary vein isolation (CPVI) remains suboptimal in patients with paroxysmal and persistent atrial fibrillation; moreover, the detection of low voltage areas (LVA) in the left atrium does predict an even higher recurrence rate of atrial tachyarrhythmias after the procedure. Left ventricular wall thickening (LVWT) is known to correlate with left atrial volume; however, no data is available whether LVWT is predictive of the presence of left atrial LVA. Purpose The aim of this study was to investigate whether LVWT is predictive of left atrial LVA and to verify that the presence of LVA confer a higher arrhythmia recurrence rate after catheter ablation for atrial fibrillation. Methods A total of 374 patients who undervent CPVI with the use of 3D electroanatomical mapping system as a primary procedure were enrolled in the study. Transthoracic echocardiography was performed in all patients prior the procedure with measurement of the thickness of the septum and the posterior wall. Patients were classified based on LVWT as normal (females:≤9mm, males:≤10mm), borderline (females:10-11mm, males: 11-12mm) and increased (females:≥12mm, males:≥13mm). A detailed left atrial voltage map was obtained in all patients prior to ablation with the identification of LVA (bipolar voltage <0.5mV with an area >5cm2). Arrhythmia recurrence was defined as documented atrial fibrillation or atrial tachycardia lasting for at least 30 seconds. Results Among 374 patients (mean age: 59.0±10.2 years, 131 females) 94, 195 and 85 were considered to be normal, borderline and increased based on LVWT, respectively. LVA were found in 29.9% (112/374) of patients. According to LVWT, LVA were detected in 16.0% (15/94), 31.3% (61/195) and 42.4% (36/85) in patients with normal, borderline and increased wall thickness, respectively, p=0.005. Patients with left atrial LVA had a higher [60.7% (68/112)] arrhythmia recurrence compared to those without low voltage areas [35.1% (92/262)] during a mean follow-up of 2.1±1.9 years, p<0.0001. Conclusions Left ventricular wall thickening predicts the presence of left atrial low voltage areas in patients undergoing catheter ablation for atrial fibrillation. Low voltage areas confer a higher arrhyhtmia recurrence rate during follow-up.

Decreased Ubiquitination and Acetylation of Histones 3 and 4 Are Associated with Obesity-Induced Disorders of Spermatogenesis in Mice.

Obesity, a chronic metabolic disorder, is related to cardiovascular diseases, diabetes, cancer, and reproductive disorders. The relationship between obesity and male infertility is now well recognized, but the mechanisms involved are unclear. We aimed to observe the effect of obesity on spermatogenesis and to investigate the role of histone ubiquitination and acetylation modifications in obesity-induced spermatogenesis disorders. Thirty male C57BL/6J mice were randomly divided into two groups. The control group was fed with a general maintenance diet (12% fat), while a high-fat diet (HFD) group was fed with 40% fat for 10 weeks; then, they were mated with normal females. The fertility of male mice was calculated, testicular and sperm morphology were observed, and the expression levels of key genes and the levels of histone acetylation and ubiquitination modification during spermatogenesis were detected. The number of sperm was decreased, as well as the sperm motility, while the number of sperm with malformations was increased. In the testes, the mRNA and protein expression levels of gonadotropin-regulated testicular RNA helicase (GRTH/DDX25), chromosome region maintenance-1 protein (CRM1), high-mobility group B2 (HMGB2), phosphoglycerate kinase 2 (PGK2), and testicular angiotensin-converting enzyme (tACE) were decreased. Furthermore, obesity led to a decrease in ubiquitinated H2A (ubH2A) and reduced levels of histone H3 acetylation K18 (H3AcK18) and histone H4 acetylation K5, K8, K12, and K16 (H4tetraAck), which disrupted protamine 1 (Prm1) deposition in testis tissue. These results suggest that low levels of histone ubiquitination and acetylation are linked with obesity-induced disorders during spermatogenesis, contributing to a better understanding of obesity-induced damage to male reproduction.

IVF exposure induced intergenerational effects on metabolic phenotype in mice

Research questionWhat is the potential transmission of metabolic phenotype from IVF offspring to the subsequent generation? DesignAn IVF mouse model was established. The F1 generation mice were produced though IVF or natural mating and the F2 generation was obtained through the mating of F1 generation males with normal females. Their metabolic phenotype, including systemic and hepatic glucolipid metabolism, was examined. ResultsIt was found that IVF F1 males exhibited metabolic changes. Compared with the control group, the IVF F1 generation showed increased body weight, elevated fasting glucose and insulin, and increased serum triglyceride concentrations. IVF F1 mice also showed an increased expression of hepatic lipogenesis and autophagy genes. Moreover, IVF F1 males transmitted some metabolic changes to their own male progeny (IVF F2) in the absence of a dietary challenge. IVF F2 mice had increased peri-epididymal and subcutaneous fat and decreased insulin sensitivity. Under the ‘second hit’ of a high-fat diet, IVF F2 mice further showed increased hepatic lipid deposition with unaltered autophagy levels. ConclusionThis research demonstrates the impact of IVF on hepatic glucose–lipid metabolism in two successive generations of offspring, highlighting the need for additional investigation. Enhanced understanding of the mechanisms underlying the transmission of multigenerational effects induced by IVF could potentially lead to the advancement of therapeutic interventions for individuals experiencing infertility.

25(OH) Vitamin D Status among Females with Preeclampsia/Eclampsia: A Long-term Plight Readdressed

Background: Preeclampsia is a life-threatening multisystem disorder of pregnancy which has been observed in 2%–10% of pregnancies. The prevalence of Vitamin D deficiency ranges from 15% to 80%. Deficiency of Vitamin D is associated with the development of preeclampsia. This study was done to find out the prevalence of Vitamin D deficiency among preeclamptic/eclamptic and normal pregnant females, to establish Vitamin D deficiency as a causal factor of preeclampsia, and to elucidate the relation between 25 (OH) Vitamin D status and the severe preeclampsia. Materials and Methods: Blood samples were collected from 50 normotensives (controls) and 50 hypertensive pregnant females with preeclampsia/eclampsia (cases), and 25 (OH) Vitamin D level was measured by chemiluminescence Immunoassay. Results: Among the preeclamptic/eclamptic group, 32 (64%) were noted with Vitamin D deficiency and 18 (36%) with Vitamin D insufficiency. In the control group, 30 (60%) pregnant women showed Vitamin D deficiency, 19 (38%) with Vitamin D insufficiency, and a sufficient level of Vitamin D was observed in one woman (2%). Conclusion: Although it is difficult to demonstrate the correlation between Vitamin D levels and preeclampsia, there is a widespread global prevalence of Vitamin D deficiency during pregnancy. Hence, Vitamin D supplementation can be included routinely in the antenatal care program in India.

Early Sex Differentiation of Climbing Perch (Anabas testudineus Bloch.): A Pathway to Feminization

The phenomenon of sexual dimorphism in climbing perch, which shows that female fish grow faster than males, underlies the development of mono-sex culture. Female mono-sex culture is more applicable for farmers by crossing neo-male fish with normal females. The timing of sexual differentiation in climbing perch is still unknown. It is very useful in sex reversal procedures to produce neo-male climbing perch. This study revealed the time and status of climbing perch sexual differentiation. Ten samples of climbing perch from the spawning of five pairs of parents were taken from the nursery pond at 10–29 days post-hatching (dph). Samples were prepared through a histology preparation procedure. Observations of the structure and characteristics of the gonads were carried out using a light microscope and analyzed histologically. The results indicated that gonad samples aged 10, 11, 12, 13, 15, and 16 dph showed primordial germ cells surrounded by somatic tissue forming genital ridges and mitotic division. Meanwhile, the gonads begin to differentiate as ovaries found at 18 dph with the presence of oogonia and ovarian cavities. Gonads aged 20–21 dph increasingly showed single oogonia cells (size 20–37.5 µm), germ cell cysts, genital ridges, oocytes undergoing the vitellogenesis process, perinucleolar oocytes, and the formation of the ovarian cavity. Sex differentiation of climbing perch was predicted from 18–21 dph. This conclusion underlies that the sex reversal procedure in climbing perch must be carried out before 18 dph.

A RARE CASE OF OVARIAN AGENESIS AND HYPOPLASTIC UTERUS IN A PREPUBERTALGIRL WITH NORMAL 46, XX KARYOTYPE

Delayed onset of puberty and primary amenorrhea pose diagnostic challenges, often associated with diverse etiologies including hypothalamic-pituitary disorders, gonadal dysgenesis, and müllerian duct malformations.Historically, such syndromes have been associated with XY chromosomal components, but rare cases in karyotypically normal females (46, XX) have been reported. Comparisons with similar cases, including atypical forms of Mayer-Rokitansky-Küster-Hauser (MRKH) syndromeare made, highlighting the rarity of this condition. Despite advancements, the genetic basis remains unspecified, underscoring the need for further research. We present a unique case of gonadal agenesis and hypoplastic uterus in a 46,XX individual, without associated organ system anomalies, contributing to primary amenorrhea. Diagnostic evaluations including hormonal assessment, and pelvic MRI confirmed the absence of ovaries and severe hypoplasia of paramesonephric duct (PMND) derivatives. Treatment with 17beta estradiol successfully induced puberty, highlighting the clinical importance of timely intervention. Early detection of such cases is crucial for providing comprehensive support and improving patient outcomes.

Loss of KLF15 impairs endometrial receptivity by inhibiting EMT in endometriosis.

The impaired endometrial receptivity is a major factor contributing to infertility in patients with endometriosis (EM), but the underlying mechanism remains unclear. Our study aimed to investigate the role of Kruppel-like factor 15 (KLF15) in endometrial receptivity and its regulation in EM. We observed a significant decrease in KLF15 expression in the mid-secretory epithelial endometrial cells of EM patients compared to normal females without EM. To confirm the role of KLF15 in endometrial receptivity, we found a significantly reduced KLF15 expression and a significant decrease in embryo implantation number in the rat model via uterine horn infection with siRNA. This highlights the importance of KLF15 as a regulator receptivity. Furthermore, through ChIP-qPCR, we discovered that the progesterone receptor (PR) directly binds to KLF15 promoter regions, indicating that progesterone resistance may mediate the decrease in KLF15 expression in EM patients. Additionally, we found that the mid-secretory endometrium of EM patients exhibited impaired epithelial-mesenchymal transition (EMT). Knockdown of KLF15 upregulated E-cadherin and downregulated vimentin expression, leading to inhibited invasiveness and migration of Ishikawa cells. Overexpression KLF15 promotes EMT, invasiveness, and migration ability, and increases the attachment rate of JAR cells to Ishikawa cells. Through RNA-seq analysis, we identified TWIST2 as a downstream gene of KLF15. We confirmed that KLF15 directly binds to the promoter region of TWIST2 via ChIP-qPCR, promoting epithelial cell EMT during the establishment of endometrial receptivity. Our study reveals the involvement of KLF15 in the regulation of endometrial receptivity and its downstream effects on EMT. These findings provide valuable insights into potential therapeutic approaches for treating non-receptive endometrium in patients with EM.

Supported to perform: sports bras and breast volume do not impair cycling performance in females.

Despite the importance of sports bras for comfort during exercise in people with breasts, concerns persist regarding their potential effects on athletic performance. Discrepancies in previous studies necessitate a closer examination of the interaction between sports bras, breast volume, exertional symptoms, and exercise performance. Twenty-three recreationally-active, normal bodyweight females completed three 10-km time-trials on a cycle ergometer on three separate occasions in a randomized order, while wearing a professionally fitted high-support sports bra, a professionally fitted low-support sports bralette, or a personal, self-selected sports bra. Performance was quantified as the time to complete the 10-km distance. Cardiorespiratory and symptom responses were measured throughout. Participants were grouped by their estimated breast volumes (small: mean ± SD 284 ± 38 ml, median bra size: 32C; large: 560 ± 97 ml, 34DD; p = 0.002, g = 3.84). The average time-trial duration was 23.1 ± 3.1 min and comparable across breast volume groups and sports bra conditions (between-group: p = 0.794, η p 2 < 0.01; between-bras: p = 0.273, η p 2 < 0.01). Notably, larger-breasted participants experienced stronger symptoms of chest tightness (p = 0.042, η p 2 = 0.18), which were associated with their ratings of perceived exertion and breathlessness (intensity and unpleasantness). Irrespective of breast volume, the high-support sports bra also evoked stronger symptoms of chest tightness (p = 0.039, η p 2 = 0.15). Stronger symptoms of chest tightness associated with larger breast volumes or high-support sports bras do not impede performance during self-paced non-weight-bearing exercise in recreationally-active females.