Follicle-stimulating Hormone Research Articles

Activins and Inhibins in Cardiovascular Pathophysiology

Activins and inhibins, members of the transforming growth factor β (TGFβ) superfamily, were initially recognized for their opposing effects on the secretion of follicle-stimulating hormone. Subsequent research has demonstrated their broader biological roles across various tissue types. Primarily, activins and inhibins function through the classical TGFβ SMAD signaling pathway, but studies suggest that they also act through other pathways, with their specific signaling being complex and context-dependent. Recent research has identified significant roles for activins and inhibins in the cardiovascular system. Their actions in other systems and their signaling pathways show strong correlations with the development and progression of cardiovascular diseases, indicating potential broader roles in the cardiovascular system. This review summarizes the progress in research on the biological functions and mechanisms of activins and inhibins and their signaling pathways in cardiovascular diseases, offering new insights for the prevention and treatment of cardiovascular diseases.

Assessment of Sex Hormones (FSH, LH, Prolactin, Estrogen, Progesterone and Testosterone) of Pulmonary Tuberculosis Patients

Background: Tuberculosis (TB) is a one of the major global health problems ranking as the eighth leading cause of death in low- and middle-income countries. This study was carried out to evaluate the Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), Prolactin, Estrogen, Progesterone and Testosterone of pulmonary tuberculosis patients in Edo State. Objectives: The objectives of the study are to assess the FSH, LH, Prolactin, Estrogen, Progesterone and Testosterone levels of Pulmonary Tuberculosis (PTB) patients compared with control, hormonal levels of PTB patients of new case, 2 months and 6 months therapy compared with control, hormonal levels of PTB patients in relation to gender and hormonal levels of PTB patients in relation to age. Material and methods: A total of 120 samples were used in this study comprising PTB new cases (30), PTB 2 months therapy (30), PTB 6 months therapy (30) and Control (30) respectively. FSH, LH, Prolactin, Estrogen, Progesterone and Testosterone were measured by Enzyme-Linked Immunoassay Test (ELISA). The results were presented using tables as mean ± standard deviation. Statistical analysis was done using one-way Analysis of Variance (ANOVA) and the student’s t-test. Significant difference was accepted at p<0.05. Results: The results obtained showed that the FSH (mIU/ml) of new case subjects, 2 months on therapy, 6 months on therapy and control were 13.42±3.58, 11.38±3.04, 6.52±2.57 and 8.71±3.15; LH (mIU/ml) was 10.43±2.95, 8.32±2.44, 5.21±2.23 and 6.05±2.44; prolactin (µg/L) was 10.17±4.04, 9.47±2.56, 10.11±6.74 and 12.96±7.09; estrogen (pg/ml) was 35.97±9.27, 41.50±12.65, 57.60±17.46 and 64.97±29.24, progesterone (ng/ml) was 0.18±0.05, 0.25±0.06, 0.40±0.10 and 0.37±0.08; and testosterone (ng/ml) was 2.49±0.95, 2.48±1.46, 4.00±2.92 and 4.32±3.84 respectively. Conclusion: In conclusion, there was significant difference (p<0.05) in the FSH, LH, Prolactin, Estrogen, Progesterone and Testosterone of the subjects in the different groups compared with control. FSH, LH, Prolactin, Estrogen and Progesterone were significantly higher (p<0.05) in female subjects compared with male subjects, while Testosterone was non-significantly (p>0.05) higher in male subjects compared with female subjects.

Assessment of Dietary Patterns in Thyroid Patients in Zawia City, Libya

Hormonal abnormalities, especially those related to follicle-stimulating hormone (FSH). This study seeks to examine the relationships of BMI, dietary patterns, seafood intake, FSH levels, and genetic variables in patients with thyroid conditions. This cross-sectional study encompassed 94 patients with thyroid conditions. BMI was categorized into four classifications (<17, 17–19, 20–25, >25), and dietary patterns were divided into conventional, balanced, specific diets, and others. Seafood consumption was classified as daily, weekly, seldom, infrequently, or never. FSH levels were categorized into five ranges. Statistical analysis was conducted to evaluate the correlations among these characteristics. A significant correlation was seen between BMI and FSH levels (p = 0.000041), with people exhibiting a BMI <17 demonstrating elevated FSH levels (>15 in 10 participants). Individuals with a BMI exceeding 25 demonstrated reduced FSH levels (ranging from 1 to less than 5 in 18 subjects). Seafood consumption significantly influenced FSH levels (p = 0.002334), with weekly consumers exhibiting a wide range of FSH values, whereas infrequent or non-consumers demonstrated elevated FSH levels (>15 in 5 subjects). Concerning dietary patterns, 60.63% adhered to a conventional diet, whereas 67% of patients have a familial history of thyroid disorders. Furthermore, 48.2% of subjects had second-degree obesity. This study highlights the intricate relationship among BMI, dietary habits, seafood intake, and hormonal regulation in patients with thyroid conditions. These factors, in conjunction with genetic predispositions, must be taken into account in the management of thyroid problems to enhance patient outcomes.

Impact of adalimumab on erectile dysfunction, sperm parameters and hormonal profile in male psoriasis patients: a six-month observational study.

Psoriasis, a chronic inflammatory skin disease, is associated with systemic complications that extend beyond cutaneous lesions, including cardiovascular risks and sexual dysfunction. Erectile dysfunction (ED) is notably more prevalent in male psoriasis patients, likely driven by both systemic inflammation and psychological stress. Adalimumab (ADA), a tumor necrosis factor-alpha (TNF-α) inhibitor, has been shown to effectively reduce psoriasis severity, but its effects on sexual and reproductive health remain underexplored. This study investigates the impact of ADA on erectile function, sperm parameters, and hormonal profiles in male psoriasis patients. This six-month prospective observational study included 33 biologic-naïve male patients aged 18-50 years with moderate-to-severe plaque psoriasis (Psoriasis Area and Severity Index [PASI] > 10). Patients received ADA according to standard clinical protocols. Erectile function was assessed using the International Index of Erectile Function (IIEF-5). Sperm parameters, including ejaculate volume, sperm concentration, total sperm count, motility, vitality, and morphology, were analyzed following World Health Organization (WHO) 2010 criteria. Hormonal profiles (testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, and prolactin) were measured via standardized assays. Statistical analyses were performed using paired t-tests or Wilcoxon signed-rank tests, with p-values < 0.05 considered significant. ADA significantly improved erectile function, as the mean IIEF-5 score increased from 21.3 ± 2.2 to 22.2 ± 1.9 (p = 0.03). The percentage of patients with ED decreased from 51.5% at baseline to 36.4% post-treatment (p < 0.001). Progressive sperm motility and vitality showed statistically significant improvement post-treatment (p = 0.02 and p = 0.04, respectively), while other sperm parameters remained unchanged. Total testosterone levels significantly increased from 3.4 ± 0.4 ng/ml to 3.5 ± 0.4 ng/ml (p = 0.02), while LH, FSH, estradiol, and prolactin levels showed no significant changes. The anti-inflammatory properties of adalimumab, through the inhibition of TNF-α, not only reduce psoriasis severity but also appear to exert positive effects on male sexual and reproductive health. Our study demonstrated significant improvements in erectile function, sperm motility, vitality, and testosterone levels in male psoriasis patients after adalimumab therapy. These findings suggest that beyond its role in controlling psoriatic skin lesions, adalimumab may help mitigate the systemic inflammatory burden that contributes to sexual dysfunction and impaired spermatogenesis. Future long-term studies are essential to further explore the sustained impact of TNF-α inhibition on male fertility and reproductive outcomes.

Gene-dose-dependent reduction of Fshr expression improves spatial memory deficits in Alzheimer's mice.

High post-menopausal levels of the pituitary gonadotropin follicle-stimulating hormone (FSH) are strongly associated with the onset of Alzheimer's disease (AD). We have shown recently that FSH directly activates the hippocampal FSH receptors (FSHRs) to drive AD-like pathology and memory loss in mice. To unequivocally establish a role for FSH in memory loss, we depleted the Fshr on a 3xTg background and utilized Morris Water Maze to study deficits in spatial memory. 3xTg;Fshr+/+ mice displayed impaired spatial memory at 5 months of age. The loss of memory acquisition and retrieval were both rescued in 3xTg;Fshr-/- mice and, to a lesser extent, in 3xTg;Fshr+/- mice-documenting clear gene-dose-dependent prevention of spatial memory loss. Furthermore, at 5 and 8 months, sham-operated 3xTg;Fshr-/- mice showed better memory performance during the learning and/or retrieval phases, further suggesting that Fshr deletion prevents age-related progression of memory deficits. This prevention was not seen when mice were ovariectomized, except in the 8-month-old 3xTg;Fshr-/- mice. There was also a gene-dose-dependent reduction mainly in the amyloid β40 isoform in whole brain extracts. Finally, serum FSH levels <8 ng/mL in 16-month-old APP/PS1 mice were associated with better retrieval of spatial memory. Collectively, the data provide compelling genetic evidence for a protective effect of inhibiting FSH signaling on the progression of spatial memory deficits in mice and lay a firm foundation for the use of an FSH-blocking agent for the early prevention of memory loss in post-menopausal women.

Microdissection testicular sperm extraction outcomes in azoospermic patients post-orchidopexy surgery: A systematic review and meta-analysis.

Cryptorchidism is a common cause of male infertility, often necessitating microdissection testicular sperm extraction (m-TESE) for sperm retrieval post-surgery. However, uncertainties persist regarding m-TESE outcomes and influencing factors following cryptorchidism surgery. A systematic review and meta-analysis were conducted to evaluate sperm retrieval rates (SRR) among patients undergoing m-TESE after cryptorchidism surgery. Factors including age at orchidopexy, age at m-TESE, type of cryptorchidism, serum hormone levels, testicular volume, and interval from surgery to m-TESE were analyzed for their impact on SRR.Nine studies encompassing 935 patients were included. The overall SRR was 57% (95% confidence interval [CI] 51% to 63%). Compared to patients with negative sperm retrieval (SR-), patients with positive sperm retrieval (SR+) underwent m-TESE at an older age (1.81 years; 95% CI 1.17 to 2.45) and orchidopexy at a younger age (-3.35 years; 95% CI -6.34 to -0.36). Different types of cryptorchidism (including high scrotal, inguinal canal, intra-abdominal) significantly influenced SRR (P<0.05). Serum testosterone, follicle-stimulating hormone, luteinizing hormone levels and testicular volume showed no significant correlation with SRR (P>0.05). Furthermore, SR- patients typically experienced shorter intervals from orchidopexy to m-TESE compared to SR+ patients (34.09 months; 95% CI 0.40 to 67.77). Earlier orchidopexy and much later m-TESE procedures, as well as undescended testis closer to the scrotum, increase the likelihood of successful sperm retrieval. Orchidopexy for cryptorchidism should be done as early as possible, whether it is performed before 18 months of age or detected at a much older age. In patients with undetected cryptorchidism and azoospermia after puberty, m-TESE should not be performed immediately after orchidopexy, the optimal interval from orchidopexy to m-TESE still requires further study.

Study on gut microbiota and metabolomics in postmenopausal women.

Menopausal syndrome, occurring during the menopausal stage in women, manifests as symptoms stemming from decreased estrogen levels, such as hot flashes, insomnia, mental disorders (anxiety, depression), and osteoporosis. The bulk of studies have indicated alterations in the gut microbiota of those experiencing menopause syndrome compared to healthy women. However, This article focuses on the alterations in gut microbiota in perimenopausal women. Our study utilized 16s rRNA sequencing to determine the differences in the gut microbiota and metabolites among 44 menopausal syndrome women. The distribution of gut microbiota in postmenopausal women varies based on the level of follicle stimulating hormone, with changes in gut microbiota abundance taking precedence over symptom onset. Fecal metabolites reveal changes in several metabolites, including Amino acid metabolism (Tyrosine, Tryptophan), Lipid metabolism (Alpha linolenic acid metabolism), and other metabolites. Disturbances in lipid metabolism, triggered by hormonal level fluctuations, can contribute to the development of osteoporosis.

Polysaccharides from Cordyceps cicadae Ameliorate Reproductive Impairments in Male Mouse through the Hypothalamic-Pituitary-Testicular Axis.

Cordyceps cicadae polysaccharides have received attention due to their potential in treating hyperglycemia and enhancing renal function. The beneficial effect of the purified C. cicadae polysaccharides fraction (CCP-1) on the reproductive impairments and spermatogenesis dysfunction of immunocompromised mice is unavailable and is studied herein. The study establishes a GC-1 spg cell apoptosis model induced by TNF-α+SM-164 (TS) and male mouse reproductive injury model induced by cyclophosphamide (CTX), and then intervened by CCP-1. CCP-1 improves the viability of GC-1 spg cell and inhibits cells apoptosis induced by TS in vitro. CCP-1 enhances sperm quality and spermatogenesis function, as well as ameliorating the histological lesions in the hypothalamus, testicular, and kidney. CCP-1 elevates gonadotropin-releasing hormone (GnRH) level that secreted by the hypothalamus, and increases the levels of follicle stimulating hormone (FSH) and luteizing hormone (LH) in the anterior pituitary stimulated by GnRH, and promotes the secretion of testosterone (T) by testis. Moreover, CCP-1 could protect the reproductive system by activating reproductive regulatory pathway such as SCF/C-kit pathway and inhibiting apoptotic signaling pathway such as Bax/Caspase-3 pathway. These results manifest that CCP-1 could serve as a natural promising reproductive system protective supplement for ameliorating CTX biotoxicity.

Lactobacillus helveticus HY7801 Improves Premenstrual Syndrome Symptoms by Regulating Sex Hormones and Inflammatory Cytokines in a Mouse Model of Metoclopramide-Induced Hyperprolactinemia

Background/Objectives: Premenstrual syndrome (PMS), a clinical condition that manifests in the form of various physical and psychological symptoms, occurs periodically during the luteal phase of the menstrual cycle and reduces quality of life. Methods: Here, we conducted in vitro and in vivo experiments to investigate the effects of Lactobacillus helveticus HY7801 (HY7801) on PMS symptoms. Results: Data from the in vitro experiments showed that HY7801 inhibits prolactin secretion by estradiol-induced GH3 cells, as well as the secretion of pro-inflammatory cytokines by LPS-induced Raw 264.7 cells. Additionally, the oral administration of HY7801 (109 colony-forming units/kg/day) to mice with metoclopramide-induced hyperprolactinemia reduced uterine tissue mass and endometrial thickness, both of which were increased excessively in the presence of prolactin. HY7801 also regulated the serum levels of follicle-stimulating hormone and prostaglandin E1/E2, as well as recovering the progesterone/estradiol ratio. HY7801 also downregulated the serum levels of prolactin and pro-inflammatory cytokines such as interleukin (Il)-6, tumor necrosis factor-alpha (Tnf), and IL-1β. Finally, HY7801 reduced the expression of genes encoding inflammatory cytokines (i.e., Tnf and Il-6), cyclooxygenase-2 (Cox-2), and inducible nitric oxide synthase (iNOS) in mice with hyperprolactinemia. Conclusion: In summary, HY7801 may be a functional bacterium that alleviates PMS symptoms by modulating hormones and inflammatory markers.

CART (Cocaine- and Amphetamine-Regulated Transcript): A New Identified Intrafollicular Mediator in Ovulation Induction Protocols

Background/Objectives: This study investigates the relationship between cocaine- and amphetamine-regulated transcript (CART) expression, leptin, and hormone profiles—specifically progesterone, testosterone, androstenedione, estradiol, follicle-stimulating hormone (FSH), and human chorionic gonadotropin (hCG)—across four distinct ovulation induction protocols (HMG, HMG/hCG, rFSH, and rFSH/hCG). It also investigates the relationship between follicle-stimulating hormone receptor (FSHR) Ser680Asn polymorphisms, CART expression, and in vitro fertilization (IVF) results, with the goal of better understanding how CART and FSHR polymorphisms affect ovarian response and oocyte quality. Methods: Data were obtained from 94 women who underwent controlled ovarian stimulation (COS) as part of their IVF therapy. Hormone levels, CART expression, and FSHR polymorphisms were measured across all four ovulation induction procedures. Statistical studies were undertaken to investigate the relationships between CART expression, hormone levels, and IVF results. Results: The study found no significant difference in body mass index (BMI) amongst the four stimulation procedures (p-values varied from 0.244 to 0.909). CART expression did not show a significant correlation with hormone levels throughout the whole cohort (progesterone, testosterone, androstenedione, FSH, hCG, and estradiol; p &gt; 0.05). However, CART levels were adversely linked with the number of follicles &gt; 12 mm (r = −0.251, p = 0.018), total oocyte count (r = −0.247, p = 0.019), and oocyte maturity (r = −0.212, p = 0.048). Furthermore, there was a strong negative connection between CART expression and thyroid hormone T3 (r = −0.319, p = 0.048). Among FSHR polymorphisms, the SER/SER genotype was related to greater CART levels (mean 4.198 ± 2.257) than the SER/ASN and ASN/ASN genotypes (p = 0.031). Conclusions: These data indicate that CART expression and FSHR polymorphisms may influence ovarian response and oocyte quality in IVF patients, possibly acting as biomarkers for evaluating ovarian outcomes in various ovulation induction procedures.

Germ Cell Dysfunction is Universal in Male Patients with β-Thalassemia Following Hematopoietic Stem Cell Transplantation During Childhood and Adolescence.

To assess gonadal function in adolescent male patients with β-thalassemia who underwent successful hematopoietic stem cell transplantation (HSCT) during childhood or adolescence. Fifty-two male patients with β-thalassemia, aged ≥10 years, who had undergone HSCT ≥2 years were included. Clinical data, such as age, genital Tanner (GT) stage at HSCT and enrollment, serum ferritin levels, and cumulative doses of alkylating agents, were collected. Gonadal function was evaluated through measurements of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, inhibin B levels, and semen analysis. Age at enrollment and HSCT were 17 (10-31) and 9 (1-19) years, respectively. The duration from HSCT to enrollment was 7.5 (2-20) years. Of 52 patients, 46 (88%) exhibited Sertoli cell dysfunction. Thirty-one patients had relatively small testes for their GT stage, 34 of 44 with GT V had elevated FSH of ≥5 IU/L, and 20 of 49 with GT stages II-V had low serum inhibin B levels. None of the patients with GT stage V showed Leydig cell dysfunction or gonadotropin deficiency. Serum FSH ≥8 IU/L showed the best diagnostic accuracy for detecting oligo- and azoospermia. All 39 patients who underwent semen analysis had >1 abnormal parameters. Having relatively small testes for GT stage and serum FSH ≥8 IU/L were associated with oligo- and azoospermia (p <0.01). Male patients with β-thalassemia after HSCT experienced universal spermatogenesis impairment and frequent Sertoli cell dysfunction but their Leydig cell function appears to be preserved. The high likelihood of future subfertility should be informed before HSCT.

Total antioxidant capacity status in non-obese adolescent females with PCOS: a cross-section study

Abstract Background The endocrine disease polycystic ovarian syndrome (PCOS) has a number of complications. Teenagers all over the globe are becoming increasingly concerned about the syndrome. It has been suggested that oxidative stress plays a significant role in the pathogenesis of PCOS. Aim The purpose of the present work was to estimate total antioxidant capacity (TAC) in non-obese adolescents and decide if the TAC could be a potential marker for the prediction and diagnosis of PCOS. Methods Serum samples were collected to assess the levels of follicle stimulant hormone (FSH), luteinizing hormone (LH), serum lipids, and serum total antioxidant capacity (TAC) in 50 non-obese patients with PCOS and 50 controls; correlation analysis was made between serum lipid, hormonal parameters, and TAC. Results Adolescents with PCOS had significantly lower levels of TAC compared with controls and showed significant higher values of LH, FSH, and LH/FSH ratio. There were significant negative correlations between TAC levels with LH, FSH, and LH/FSH. Linear regression analysis revealed statistically significant correlations between TAC and LH and FSH levels in non-obese adolescents with PCOS. Conclusion Serum TAC level was diminished in non-obese PCOS patients and was related to increase of LH/FSH ratio. So, quantification of TAC activity in serum could be of value in assessment of cases at higher risk for development of PCOS, suggesting its possible role in regulating sex hormones and could have potential roles in the etiopathogenesis of PCOS in non-obese adolescent females.

Electroacupuncture at acupoints of liver meridian for diminished ovarian reserve of liver depression: a randomized controlled trial

To observe the therapeutic effect of electroacupuncture at acupoints of liver meridian in patients with diminished ovarian reserve (DOR) of liver depression. A total of 62 patients with DOR of liver depression were randomly divided into an electroacupuncture group (31 cases, 1 case discontinued) and a western medication group (31 cases, 1 case was eliminated). Electroacupuncture was applied at bilateral Taichong (LR 3), Ligou (LR 5), Ququan (LR 8), Jimai (LR 12) in the electroacupuncture group, with continuous wave, in frequency of 2 Hz and current of 0.5-1.0 mA, 30 min each time, once every other day, 3 times a week. Femoston was taken orally in the western medication group, oral estradiol tablets were taken for the first 14 days, followed by oral estradiol/progesterone complex tablets for the rest 14 days, 1 tablet a day. Both groups were treated for 3 consecutive menstrual cycles. Before and after treatment, the scores of TCM syndrome, self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were observed, serum levels of follicle stimulating hormone (FSH) and anti-Müllerian hormone (AMH) were detected, and antral follicle count (AFC), peak systolic velocity (PSV) and resistance index (RI) of ovarian artery were measured by color Doppler ultrasound in the two groups, and the clinical efficacy was evaluated after treatment. After treatment, the scores of primary symptom and secondary symptom, as well as the total scores of TCM syndrome were decreased compared with those before treatment (P<0.01), the scores of SAS and SDS, as well as the serum FSH levels and RI of ovarian artery were decreased compared with those before treatment (P<0.01), while the serum AMH levels, AFC and PSV of ovarian artery were increased compared with those before treatment (P<0.05, P<0.01) in the two groups. After treatment, in the electroacupuncture group, the primary symptom score of TCM syndrome was higher than that in the western medication group (P<0.01), the secondary symptom score of TCM syndrome and the scores of SAS and SDS were lower than those in the western medication group (P<0.05, P<0.01). The total effective rate was 70.0% (21/30) in the electroacupuncture group and 73.3% (22/30) in the western medication group respectively, there was no significant difference in the total effective rate between the two groups (P>0.05). Electroacupuncture at acupoints of liver meridian can effectively improve the clinical symptoms, anxiety and depression, regulate the serum sex hormone levels, increase AFC and improve ovarian blood supply in DOR patients of liver depression.

Radiation-induced Ovarian Ablation and Survival in Breast Cancer: A Single-Institutional Evaluation

ABSTRACT Background: Radiation-induced ovarian ablation (ROA) was one of the main modalities in the early years in inducing suppression of hormone levels of estradiol (E2) and follicle-stimulating hormones (FSHs) in estrogen receptor/progesterone receptor-positive breast cancer patients. However, as newer techniques such as medical ovarian suppression (MOS) and laparoscopic oophorectomies (LOs) emerged, ROA began to take a back seat. Nonetheless, ROA remains a valuable option for certain patients with specific indications. It is worth noting that ROA is still as effective as MOS and LO in achieving desired hormonal suppression levels. Materials and Methods: After receiving approval from the institutional ethics committee, we enrolled 41 female breast cancer patients who were scheduled for ROA at our institute between 2016 and 2018. Two patients declined to participate and were, therefore, excluded from the final analysis. Patients were evaluated for pre- and postradiation hormone levels, specifically E2 and FSH, cessation of menstrual periods, radiation-induced toxicity, disease-free survival (DFS), overall survival (OS), and the clinical profile as well. Results: Among 39 patients, 89.74% (n = 35) achieved postmenopausal hormone levels after ROA. Only 17.94% (n = 7) patients were menstruating before radiation exposure to the pelvis (postchemotherapy) and among these, 3 patients (42.85%) attained amenorrhea after ROA. The mean age of patients was 42 years, and the most common stage at presentation was Stage III (n = 15) 38.5%. Her2 positivity was seen in (n = 11) 28.2%. Breast conservation surgery was done in 64.1% (n = 25) and mastectomy was done in 23.1% (n = 9). About 71.7% (n = 28) have received tamoxifen, 43.5% (n = 17) were on letrozole, and 17.9% (n = 7) have received trastuzumab. None had shown any Grade 3 or 4 acute skin toxicity during treatment and late radiation-induced complications during their follow-up. The mean 5-year DFS was 62.2% and the mean 5-year OS was 59%. Conclusion: ROA is not widely used anymore due to its irreversible nature, and there are now reversible and noninvasive methods for ovarian suppression. Observing the effectiveness of ROA, it may still be an option for a selective group of breast cancer patients especially those who have contraindications for MOS or are willing for a short course of treatment.

TMOD-06. ESTABLISHMENT OF PITUITARY NEUROENDOCRINE TUMOR (PITNET) ORGANOID MODELS

Abstract Pituitary neuroendocrine tumors (PitNETs) are tumors that originate from the anterior pituitary gland. While they are mostly benign, they can cause various clinical symptoms due to hormonal secretion abnormalities. PitNET can be broadly categorized into three lineages, each of which has its differentiation controlled by specific transcription factors. Treatment options for PitNET include surgical resection and pharmacotherapy, but available drugs are limited, and their efficacy markers remain unclear. To develop novel drugs for PitNET and identify their efficacy markers, it is necessary to develop new research models. In recent years, organoid models have garnered attention as novel research models for various cancer types. In this study, we established novel organoid models derived from PitNET patients and analyzed their histological and endocrinological characteristics. Surgical specimens from 4 cases of somatotroph adenoma, 1 case of double adenoma, 1 case of gonadotroph adenoma, and 1 case of corticotroph adenoma were minced in dissection medium and embedded in Matrigel basement membrane matrix respectively. The organoids were cultured under 5% CO2 at 37°C using media supplemented with various growth factors. After 28 days of culture, formalin-fixed paraffin-embedded sections were prepared to examine histological homology with patient tumors. Hematoxylin and eosin staining results showed that all organoids maintained cell morphology and tissue structure similar to the original tumors. Immunohistochemical staining for markers specific to each PitNET revealed similar staining patterns between the organoids and the original tumors. Furthermore, analysis of hormone levels in the culture medium showed that hormone production capabilities, such as growth hormone and follicle stimulating hormone, were maintained even after long-term culture. In this study, we successfully established PitNET organoid models that retain histological and endocrinological characteristics. These models are expected to serve as useful research tools for elucidating the molecular mechanisms of PitNET and developing novel therapies targeting critical molecular abnormalities.

Association of growth differentiation factor 9 expression with nuclear receptor and basic helix-loop-helix transcription factors in buffalo oocytes during in vitro maturation.

Growth differentiation factor 9 (GDF9) is an oocyte-specific paracrine factor involved in bidirectional communication, which plays an important role in oocyte developmental competence. In spite of its vital role in reproduction, there is insufficient information about exact transcriptional control mechanism of GDF9. Hence, present study was undertaken with the aim to study the expression of basic helix-loop-helix (bHLH) transcription factors (TFs) such as the factor in the germline alpha (FIGLA), twist-related protein 1 (TWIST1) and upstream stimulating factor 1 and 2 (USF1 and USF2), and nuclear receptor (NR) superfamily TFs like germ cell nuclear factor (GCNF) and oestrogen receptor 2 (ESR2) under three different in vitro maturation (IVM) groups [follicle-stimulating hormone (FSH), insulin-like growth factor-1 (IGF1) and oestradiol)] along with all supplementation group as positive control, to understand their role in regulation of GDF9 expression. Buffalo cumulus-oocyte complexes were aspirated from abattoir-derived ovaries and matured in different IVM groups. Following maturation, TFs expression was studied at 8 h of maturation in all four different IVM groups and correlated with GDF9 expression. USF1 displayed positive whereas GCNF, TWIST1 and ESR2 revealed negative correlation with GDF9 expression. TWIST1 & ESR2 revealing negative correlation with GDF9 expression were found to be positively correlated amongst themselves also. GCNF & USF1 revealing highly significant correlation with GDF9 expression in an opposite manner were found to be negatively correlated. The present study concludes that the expression of GDF9 in buffalo oocytes remains under control through the involvement of NR and bHLH TFs.

Nutritional Status of Patients with Polycystic Ovary Syndrome (PCOS) in Irbid Governorate, Jordan: A Case-Control Study

Polycystic Ovary Syndrome (PCOS) is a crucial infertility problem among women in the world; especially Arab women. The main objective of this case-control study was to perform anthropometric, biochemical, clinical and nutritional assessment among PCOS patients. The study population composed of 60 Jordanian women aged 19–39 years, and classified into two groups: 30 were cases (PCOS patients) and 30 were control group (Healthy women). Results of the study indicated that the Body Mass Index (BMI) were significantly higher among PCOS patients than healthy women. Furthermore, significant differences were shown in the mean values of Luteinizing Hormone (LH) and (LH): Follicle-Stimulating Hormone (FSH) (LH:FSH) ratio which were higher among PCOS patients with a p=0.01 and p=0.03, respectively. Also, significant differences between PCOS patients and healthy women were shown for three clinical manifestations of PCOS including infertility, sleep apnea, and eating disorders. Moreover, the findings of the validated food frequency questionnaire (FFQ) revealed no significant differences between two study groups in the consumption of macronutrients and total energy intake. It is obviously concluded from the study that PCOS is remarkably responsible for substantial variations in anthropometric and biochemical measurements, hormonal levels, and clinical features among PCOS patients.

Fertility protective effects of Brillantaisia patula leaf extract against cyclophosphamide-induced ovarian damage in Wistar rats

BackgroundThe primary indication of infertility is the incapacity to conceive, and in females, the majority of instances of female infertility stem from ovulation disorders. This study evaluated the female fertility-enhancing effects and safety of aqueous leaf extract of Brillantaisia patula (ALEBP) in a cyclophosphamide (CYP) model of sterility in Wistar rats.MethodSixty-six female rats randomly allotted to six groups (n = 11) were administered with the appropriate regimen for 21 days and then mated with male rats. Group 1 (control) received distilled water. Groups 2–6 were treated with a single dose (200 mgkg− 1 body weight) of cyclophosphamide intraperitoneally and, in addition, received the same volume (0.5 mL) of distilled water, 18, 36, 72 mgkg− 1 body weight of ALEBP and 200 mg per body weight of vitamin C orally. Mating lasted 11 days; on day 20, the female Wistar rats were sacrificed. Data were analysed using One-way Analysis of Variance (ANOVA) followed by Dunett’s posthoc analysis, and GraphPad (at p < 0.05).ResultsResults herein showed that ALEBP significantly (p < 0.05) increased the diminution in activities/levels of glutathione peroxidase (GPx), reduced glutathione (GSH), total antioxidant capacity (TAC), cholesterol, alkaline phosphatase (ALP), acid phosphatase (ACP), estrogen (ES), and luteinising hormone (LH) induced by cyclophosphamide. ALEBP further reversed the increased level of malondialdehyde (MDA), tumour necrosis factor-α (TNFα), interleukin 8 (IL-8), and follicle-stimulating hormone (FSH) caused by cyclophosphamide (p < 0.05). In addition, ALEBP, while it significantly increased the cyclophosphamide-induced reduction in the number of implantations in each animal, the total number of viable fetuses, the total number of corpora lutea, and the fertility index, also significantly reduced the number of fetal resorptions in each animal and pre-implantation loss that was increased by cyclophosphamide. Moreover, the cyclophosphamide-induced degenerative and necrotic changes in the ovarian cells and uterus were reversed by ALEBP.ConclusionsConsidered as a whole, the aqueous leaf extract of Brillantaisia patula reversed oxidative stress and inflammatory side effects of cyclophosphamide, preserving ovarian function and fertility in the rats. This may suggest its exploration as a safe agent against toxic side effects of chemotherapy and fertility-related disorders of the uterus and ovary.

Huyang Yangkun formula regulates the mitochondria pathway of ovarian granulosa cell apoptosis through FTO/m6A-P53 pathway

BackgroundPremature ovarian insufficiency (POI) presents a significant challenge to female reproductive health. The Huyang Yangkun Formula (HYF), a traditional Chinese medicinal formulation, has been utilized in clinical settings for the treatment of POI for over a decade. Nevertheless, the therapeutic application of HYF is considerably constrained by the lack of clarity regarding its underlying mechanism of action.MethodsThe experimental procedures entailed administering VCD to female Sprague-Dawley rats at a dosage of 160 mg/kg/day over a period of 15 days, succeeded by a 100-day treatment with HYF. Blood serum samples were collected and analyzed using ELISA to quantify the concentrations of Anti-Müllerian Hormone (AMH), Follicle-Stimulating Hormone (FSH), and Estradiol (E2). The levels of N6-methyladenosine (m6A) were assessed through Dot blot analysis and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Western blotting was employed to validate the differential expression of m6A-related catalytic enzymes and apoptosis-related regulators, including BCL-2, BCL-XL, and MCL-1, which may be implicated in the effects of HYF. Certain shRNA-COV434 cell line was constructed for the exploration of molecular mechanism, and then the potential targets were finally verified by MeRIP-qPCR.ResultsHYF has been identified as having a significant influence on the development of residual ovarian follicles in rats with POI, especially during the initial stages. It was observed that HYF facilitates the progression of escaping antral follicles to full maturation. Additionally, HYF exhibited the capacity to enhance the proliferation of COV434, a human ovarian granulosa cell line, while concurrently inhibiting apoptosis within these cells. Notably, HYF treatment resulted in the downregulation of apoptotic proteins, including BCL-XL, cleaved-caspase 9, cleaved-caspase 3, and Bcl-2. Concurrently, m6A modification is implicated in the regulation of HYF. Both in vitro and in vivo studies indicate that FTO may play a role in the anti-apoptotic mechanisms mediated by m6A in ovarian granulosa cells influenced by HYF. Moreover, employing qPCR and MeRIP-qPCR techniques, P53 has been identified as the target gene for m6A modification mediated by FTO.ConclusionThese findings suggest that HYF holds promise as a potential treatment for POI and provide a more comprehensive understanding of the mechanism by which HYF operates, specifically its ability to prevent the BCL-2 mitochondrial apoptosis pathway mediated by P53 in ovarian granulosa cells of POI rats by regulating FTO/m6A-Tp53.

The effect of different doses of estradiol benzoate on follicle development and twin birth in beef cattle with induced superovulation

Abstract. The aim of this study was to evaluate the effect of different doses of estradiol benzoate (EB) on inhibiting the development of non-dominant follicles and inducing twin calves in beef heifers. Beef heifers were synchronized using estradiol plus progesterone (P4), and superovulation was induced using a small-dose follicle-stimulating hormone (FSH) protocol. From day 6.5 to day 7.5, every heifer was treated with 0, 0.1, 0.2, or 0.5 mg EB three times at 12 h intervals to eliminate excess dominant follicles. The diameters of the two largest follicles (F1 and F2) continually increased from day 3.5 to day 10. However, the growth rate was constrained by exogenous EB, and the degree of suppression was greatest in the 0.5 mg EB treatment compared with other treatments. As a result, the number of large follicles (≥10 mm) decreased as the EB dose increased. Compared with the control treatment, the incidence of animals experiencing triple ovulation was significantly lower in the 0.5 mg EB treatment; however, the single-ovulation rate showed the inverse. This study demonstrated that 0.2 mg EB could modulate the development of two to three co-dominant follicles after a small-dose FSH treatment. The number of twin births was higher in the 0.2 mg EB treatment.