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1.
Gynecol Endocrinol ; 40(1): 2358219, 2024 Dec.
Article En | MEDLINE | ID: mdl-38835150

OBJECTIVES: Polycystic ovary syndrome (PCOS) and subclinical hypothyroidism (SCH) are prevalent gynecological conditions. However, the interrelationship between the two remains elusive. This study aims to elucidate the association between these conditions and determine the potential impact of SCH on the physiological and metabolic characteristics of patients with PCOS. METHODS: This cross-sectional study enrolled 133 patients with PCOS from our Hospital. Participants were categorized into two groups: those with PCOS + SCH (n = 58) and those with PCOS (n = 75). Serum hormonal levels, metabolic markers, ovarian volume, and follicle count were compared between the groups. RESULTS: There was a significant difference in BMI between the two groups, with a higher prevalence of obesity in the PCOS + SCH group (p = .014). Compared to the PCOS group, patients with PCOS + SCH had significantly higher levels of TSH (p < .001), triglycerides (p = .025), and HOMA-IR (p < .001), while LH levels were significantly lower (p = .048). However, multivariate linear regression analysis revealed that TSH, triglycerides, LH, and HOMA-IR were not determinants for the occurrence of SCH in patients with PCOS. Additionally, there was a notable reduction in follicle count in the left ovary for the PCOS + SCH group compared to the PCOS group (p = .003), and the overall follicle diameter of the PCOS + SCH group was also smaller (p = .010). CONCLUSION: SCH may exert effects on the physiological and metabolic profiles of patients with PCOS. Further investigation into the relationship between these disorders is warranted to delineate their clinical implications.


Hypothyroidism , Ovary , Polycystic Ovary Syndrome , Humans , Polycystic Ovary Syndrome/blood , Polycystic Ovary Syndrome/metabolism , Polycystic Ovary Syndrome/complications , Female , Hypothyroidism/blood , Hypothyroidism/complications , Cross-Sectional Studies , Adult , Ovary/pathology , Ovary/metabolism , Ovary/diagnostic imaging , Young Adult , Thyrotropin/blood , Insulin Resistance/physiology , Luteinizing Hormone/blood , Body Mass Index , Triglycerides/blood , Ovarian Follicle/diagnostic imaging , Ovarian Follicle/metabolism
2.
Domest Anim Endocrinol ; 88: 106852, 2024 Jul.
Article En | MEDLINE | ID: mdl-38701638

Mares resume ovarian activity rapidly after foaling. Besides follicle-stimulating hormone (FSH) and luteinizing hormone (LH), the pituitary synthesizes prolactin and growth hormone which stimulate insulin-like growth factor (IGF) synthesis in the liver. We tested the hypothesis that follicular growth is initiated already antepartum, mares with early and delayed ovulation differ in IGF-1 release and that there is an additional IGF-1 synthesis in the placenta. Plasma concentrations of LH, FSH, IGF-1, IGF-2, activin and prolactin. IGF-1, IGF-2, prolactin and their receptors in placental tissues were analyzed at the mRNA and protein level. Follicular growth was determined from 15 days before to 15 days after foaling in 14 pregnancies. Mares ovulating within 15 days postpartum formed group OV (n=5) and mares not ovulating within 15 days group NOV (n=9). Before foaling, follicles with a diameter >1 cm were present in all mares and their number increased over time (p<0.05). Follicle growth after foaling was more pronounced in OV mares (day p<0.001, group p<0.05, day x group p<0.05) in parallel to an increase in LH concentration (p<0.001, day x group p<0.001) while FSH increased (p<0.001) similarly in both groups. Plasma concentrations of IGF-1 and prolactin peaked one day after foaling (p<0.001). The IGF-1 mRNA abundance was higher in the allantochorion but lower in the amnion of OV versus NOV mares (group p=0.01, localization x group p<0.01). The IGF-1 receptor mRNA was most abundant in the allantochorion (p<0.001) and IGF-1 protein was expressed in placental tissue without differences between groups. In conclusion, follicular growth in mares is initiated before foaling and placental IGF-1 may enhance resumption of ovulatory cycles.


Insulin-Like Growth Factor I , Ovary , Postpartum Period , Prolactin , Animals , Horses/physiology , Female , Postpartum Period/physiology , Prolactin/blood , Prolactin/metabolism , Pregnancy , Insulin-Like Growth Factor I/metabolism , Insulin-Like Growth Factor I/genetics , Ovary/physiology , Ovary/metabolism , RNA, Messenger/metabolism , RNA, Messenger/genetics , Placenta/metabolism , Luteinizing Hormone/blood , Luteinizing Hormone/metabolism , Ovarian Follicle/physiology , Ovarian Follicle/metabolism , Follicle Stimulating Hormone/blood , Follicle Stimulating Hormone/metabolism , Ovulation/physiology , Insulin-Like Growth Factor II/genetics , Insulin-Like Growth Factor II/metabolism , Activins/metabolism , Receptors, Prolactin/genetics , Receptors, Prolactin/metabolism
3.
Talanta ; 275: 126150, 2024 Aug 01.
Article En | MEDLINE | ID: mdl-38692046

The quantitative detection of luteinising hormone (LH) is critical for the study of the physiological mechanism of reproductive function and the assessment of infertility and the clinical treatment of reproductive disorders. However, conventional approaches for LH detection are mostly based on an antibody recognition module with the limitations of sensitivity, simplicity and cost. The development of robust LH sensing methods is therefore highly demanded for facilitating the diagnosis of LH-related diseases. We establish a convenient, amplified and sensitive fluorescent aptamer LH assay based on new target-triggered and cascaded autocatalytic hairpin assembly (C-aCHA) circuit amplification means via initiator sequence replication. Target LH molecules bind the aptamers in the aptamer/initiator duplexes to release the initiator sequences, which trigger CHA formation of DNA three-way junctions (TWJs) and the unfolding of fluorescently quenched signal hairpins to show amplified fluorescence. The TWJs further activate another CHA cycle for the yield of more initiator sequences to form the C-aCHA circuit amplification cycles, which lead to the unfolding of many signal hairpins to exhibit substantially magnified fluorescence recovery for detecting LH down to 8.56 pM in the range from 10 pM to 50 nM. In addition, the monitoring of trace LH in diluted serums by this sensing approach has been also verified. Our LH assay clearly outperforms current existing antibody-based methods and the C-aCHA signal amplification strategy can be easily extended as a robust means for sensitively monitoring various biomolecular markers with simple replacement of the corresponding aptamers for diverse applications.


Aptamers, Nucleotide , Biosensing Techniques , Fluorescent Dyes , Luteinizing Hormone , Aptamers, Nucleotide/chemistry , Luteinizing Hormone/blood , Luteinizing Hormone/analysis , Luteinizing Hormone/chemistry , Humans , Biosensing Techniques/methods , Fluorescent Dyes/chemistry , Nucleic Acid Amplification Techniques/methods , Inverted Repeat Sequences , Catalysis , Limit of Detection , Fluorescence
4.
Zhonghua Fu Chan Ke Za Zhi ; 59(5): 391-400, 2024 May 25.
Article Zh | MEDLINE | ID: mdl-38797569

Objective: To investigate the effect of rare ginsenosides (RGS) on reproductive injury induced by cyclophosphamide (CP) in female rats. Methods: Twenty-four female rats were divided into four groups [normal control (NC), RGS, CP, and CP+RGS group] with 6 rats in each group. CP group (the model group) and CP+RGS group (the treatment group) were intraperitoneally injected with CP 30 mg/kg for 5 days for modeling, and CP+RGS group was given RGS intragastric intervention. General growth status of rats in each group was observed, the organ index was calculated, and the pathological changes of ovary, uterus, liver and kidney were observed by hematoxylin-eosin staining. Serum levels of estradiol, follicle stimulating hormone (FSH), luteinizing hormone (LH), pro-inflammatory factors interleukin (IL) 6, IL-1ß, tumor necrosis factor-α were detected. The urine samples were collected after RGS treatment for metabonomics analysis. Metabolomic profiling based on ultra performance liquid chromatography (UPLC) coupled with mass spectrometry (MS) was used to analyze and determine the urine metabolites of rats in each group. Results: Compared with NC group, the ovary index of CP group [(0.054±0.015) %] was significantly decreased (P<0.05), the uterus index [(0.293±0.036) %] and estradiol level [(62.9±6.4) pmol/L] were significantly decreased (all P<0.01), serum levels of FSH, LH, IL-6 and IL-1ß [(20.4±1.0) U/L, (29.0±3.0) U/L, (185.4±28.6) ng/L, (72.9±2.0) ng/L, respectively] were significantly increased (all P<0.01). Compared with CP group, the ovary index in CP+RGS group [(0.075±0.010) %] was significantly increased (P<0.05), serum estradiol level [(122.1±16.2) pmol/L] was significantly increased (P<0.01), serum FSH, IL-1ß and IL-6 levels [(16.7±1.0) U/L, (111.8±17.4) ng/L, (60.1±2.2) ng/L, respectively] were significantly decreased (all P<0.01). Metabonomics analysis results showed that, a total of 352 metabolites were detected in urine, of which 12 were found to be potential markers associated with reproductive injury according to the screening standard. After treatment with RGS, differential metabolites were improved in the direction of NC group. Pathway enrichment suggests that the therapeutic effect of RGS was related to multiple metabolic pathways, including purine metabolism and taurine and hypotaurine metabolism. Conclusion: RGS might reduce inflammation and thus ameliorate the damage caused by CP to the reproductive system of female rats by affecting purine metabolism and other pathways.


Cyclophosphamide , Estradiol , Follicle Stimulating Hormone , Ginsenosides , Metabolomics , Ovary , Rats, Sprague-Dawley , Uterus , Animals , Female , Rats , Cyclophosphamide/adverse effects , Cyclophosphamide/toxicity , Ginsenosides/pharmacology , Follicle Stimulating Hormone/blood , Estradiol/blood , Ovary/drug effects , Ovary/pathology , Ovary/metabolism , Uterus/drug effects , Uterus/pathology , Uterus/metabolism , Luteinizing Hormone/blood , Chromatography, High Pressure Liquid , Interleukin-6/metabolism , Interleukin-6/blood , Disease Models, Animal , Interleukin-1beta/metabolism , Interleukin-1beta/blood , Tumor Necrosis Factor-alpha/metabolism , Tumor Necrosis Factor-alpha/blood , Liver/metabolism , Liver/drug effects , Liver/pathology , Mass Spectrometry , Kidney/drug effects , Kidney/pathology , Kidney/metabolism
5.
Zhongguo Zhong Yao Za Zhi ; 49(8): 1996-2005, 2024 Apr.
Article Zh | MEDLINE | ID: mdl-38812216

Transcriptomics was used to investigate the mechanism of action of Bushen Culuan Formula in the treatment of infertility caused by hyperprolactinemia(HPRL), and animal experiments were carried out to verify the results. After establishing an animal model of HPRL-induced infertility, the mice were divided into normal group, model group, Bushen Culuan Formula groups with high-, medium-, and low-doses, and bromocriptine group, and they were observed in terms of the estrous cycle, gonadal index, serum sex hormones, morphology of ovary and mammary gland, follicle count, and fertility. The results showed that the Bushen Culuan Formula could effectively restore the estrous cycle, down-regulate the levels of prolactin(PRL), follicle-stimulating hormone(FSH), and luteinizing hormone(LH), up-regulate the level of estradiol(E_2), increase the number of primordial follicles and sinus follicles, and improve the ovulation rate and fertility of mice. Through RNA sequencing combined with biosignature analysis, Bushen Culuan Formula may regulate the metabolism of lipids, antioxidant enzymes, and other substances in the cells of the ovary and pituitary gland through the signaling pathways of cAMP-PKA, Kiss-1/GPR54, and Hippo and exert therapeutic effects. The results of animal experiments showed that Bushen Culuan Formula could up-regulate serum dopamine(DA) level and pituitary DRD2 expression, down-regulate hypothalamus and ovary cAMP levels, as well as protein expressions of the pituitary gland and ovary PKA, CREB, and p-CREB, and treat HPRL-induced infertility by regulating the cAMP-PKA signaling pathway.


Drugs, Chinese Herbal , Gonadal Steroid Hormones , Hyperprolactinemia , Ovulation , Animals , Female , Mice , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/pharmacology , Hyperprolactinemia/drug therapy , Ovulation/drug effects , Humans , Follicle Stimulating Hormone/blood , Luteinizing Hormone/blood , Ovary/drug effects , Ovary/metabolism , Estrous Cycle/drug effects , Receptors, Dopamine D2/metabolism , Receptors, Dopamine D2/genetics
6.
Zhongguo Zhong Yao Za Zhi ; 49(8): 2006-2015, 2024 Apr.
Article Zh | MEDLINE | ID: mdl-38812217

This study aims to observe the efficacy and safety of Bushen Culuan Formula in the treatment of infertility caused by polycystic ovary syndrome(PCOS) and to explore the mechanism using metabolomics. Ninety-four patients with infertility caused by PCOS with the syndrome of kidney deficiency and blood stasis were selected and assigned into treatment and control groups(n=47). The basal body temperature(BBT) was measured, and B-ultrasonography was employed to monitor follicles, ovarian volume, endometrium, ovulation, and pregnancy. The serum levels of sex hormones including follicle-stimulating hormone(FSH), luteinizing hormone(LH), prolactin(PRL), estradiol(E_2), progestin(P), testosterone(T), free testosterone(FT), androstenedione(A2), inhibin B(INHB), and anti-Müllerian hormone(AMH) were measured. The coagulation function, traditional Chinese medicine(TCM) symptom scores, blood and urine routine, liver and kidney functions and other safety indicators were determined. Metabolomics was employed to comparatively analyze the serum metabolites of 26 patients(13 patients in each group) in the clinical study. The results showed that the total response rate and pregnancy rate of the treatment group were higher than those of the control group(P<0.001), suggesting that Bushen Culuan Formula regulated the sex hormones and ovarian function. Specifically, it reduced the levels of LH, T, FT, A2, and INHB(P<0.05 or P<0.01) and the LH/FSH ratio(P<0.05), elevated the level of P(P<0.05), promoted ovulation, increased endothelial thickness, and lowered TCM symptom scores without causing adverse reactions. A total of 24 differential metabolites were screened by metabolomics, and there were correlations between sex hormones and differential metabolites in the PCOS-induced infertility patients with kidney deficiency and blood stasis. In conclusion, Bushen Culuan Formula may regulate hormone levels through lipid and amino acid metabolism.


Drugs, Chinese Herbal , Infertility, Female , Polycystic Ovary Syndrome , Humans , Female , Polycystic Ovary Syndrome/drug therapy , Polycystic Ovary Syndrome/physiopathology , Polycystic Ovary Syndrome/complications , Drugs, Chinese Herbal/administration & dosage , Adult , Infertility, Female/drug therapy , Infertility, Female/etiology , Infertility, Female/physiopathology , Young Adult , Pregnancy , Luteinizing Hormone/blood
7.
Anal Chim Acta ; 1309: 342646, 2024 Jun 22.
Article En | MEDLINE | ID: mdl-38772670

BACKGROUND: Colorimetric lateral flow immunoassay (LFIA) is a widely used point-of-care testing (POCT) technology, while it has entered a bottleneck period because of low detection sensitivity, expensive preparation materials, and incapable quantitative detection. Therefore, it is necessary to develop a novel POCT method that is ultrasensitive, simple, portable, and capable of accurately detecting biomarkers in biofluids daily, particularly for pregnancy preparation and early screening of diseases. RESULT: In this work, a novel dry chemistry-based self-enhanced electrochemiluminescence (DC-SE-ECL) LFIA sensor is introduced for accurate POCT of luteinizing hormone (LH). The proposed DC-SE-ECL immunosensor significantly improves the detection sensitivity through the Poly-l-Lysine (PLL)-based SE-ECL probe and cathode modification of closed bipolar electrode (C-BPE). Additionally, a new type of C-BPE configuration is designed for easily performing the LFIA. And, two standalone absorbent pads are symmetrically arranged below the reporting channel of the electrode pad to decease useless residues on the detection pad, which further improves the detection performance. Under optimized conditions, the proposed LFIA sensor has a low limit of detection (9.274 µIU mL-1) and a wide linear dynamic range (0.01-100 mIU mL-1), together with good selectivity, repeatability and storage stability. SIGNIFICANCE: These results indicate that the proposed DC-SE-ECL method has the potential as a new tool for detecting biomarkers in clinical samples.


Electrochemical Techniques , Luminescent Measurements , Luteinizing Hormone , Luteinizing Hormone/analysis , Luteinizing Hormone/blood , Humans , Immunoassay/methods , Electrochemical Techniques/instrumentation , Limit of Detection , Electrodes , Biosensing Techniques
8.
Front Endocrinol (Lausanne) ; 15: 1390674, 2024.
Article En | MEDLINE | ID: mdl-38737553

Introduction: Gonadotropin-releasing hormone (GnRH) analogs are the standard treatment for central precocious puberty (CPP). Although there are numerous varieties of GnRH agonists, the effectiveness of 1-monthly compared with 3-monthly Leuprolide acetate is still restricted. The objective of this study was to evaluate the outcomes of CPP treatment with Leuprolide acetate at a 1-monthly dosage of 3.75 mg, in comparison to a dosage of 11.25 mg administered every 3 months. Method: This retrospective cohort study involved 143 girls diagnosed with CPP with 72 of them receiving the monthly treatment regimen and 71 receiving the 3-monthly treatment regimen. Anthropometric measurements were compared at the start and end of the therapy. The rates and level of LH suppression were assessed six months after therapy. Results: The regimen administered every 3 months showed more significant suppression of LH. The 3-monthly group showed lower actual height and degree of bone age advancement at the end of therapy. However, the predicted adult height (PAH) remained comparable in both groups. Conclusion: The 3-monthly treatment showed greater hormonal and growth suppression effects, but there was no significant difference in PAH between the two groups.


Leuprolide , Puberty, Precocious , Humans , Leuprolide/administration & dosage , Leuprolide/therapeutic use , Puberty, Precocious/drug therapy , Female , Retrospective Studies , Child , Treatment Outcome , Luteinizing Hormone/blood , Body Height/drug effects , Drug Administration Schedule , Gonadotropin-Releasing Hormone/agonists , Child, Preschool
9.
Mol Biol Rep ; 51(1): 656, 2024 May 13.
Article En | MEDLINE | ID: mdl-38740671

BACKGROUND: Prokineticin 2 (PROK2), an important neuropeptide that plays a key role in the neuronal migration of gonadotropin-releasing hormone (GnRH) in the hypothalamus, is known to have regulatory effects on the gonads. In the present study, the impact of intracerebroventricular (icv) PROK2 infusion on hypothalamic-pituitary-gonadal axis (HPG) hormones, testicular tissues, and sperm concentration was investigated. METHODS AND RESULTS: Rats were randomly divided into four groups: control, sham, PROK2 1.5 and PROK2 4.5. Rats in the PROK2 1.5 and PROK2 4.5 groups were administered 1.5 nmol and 4.5 nmol PROK2 intracerebroventricularly for 7 days via an osmotic mini pump (1 µl/h), respectively. Rat blood serum follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone hormone levels were determined with the ELISA method in the blood samples after 7 days of infusion. GnRH mRNA expression was determined with the RT-PCR in hypothalamus tissues. analyze Sperm concentration was determined, and testicular tissue was examined histologically with the hematoxylin-eosin staining method. It was observed that GnRH mRNA expression increased in both PROK2 infusion groups. Serum FSH, LH and testosterone hormone levels also increased in these groups. Although sperm concentration increased in PROK2 infusion groups when compared to the control and sham, the differences were not statistically significant. Testicular tissue seminiferous epithelial thickness was higher in the PROK2 groups when compared to the control and sham groups. CONCLUSION: The present study findings demonstrated that icv PROK2 infusion induced the HPG axis. It could be suggested that PROK2 could be a potential agent in the treatment of male infertility induced by endocrinological defects.


Follicle Stimulating Hormone , Gastrointestinal Hormones , Gonadotropin-Releasing Hormone , Luteinizing Hormone , Neuropeptides , Testis , Testosterone , Male , Animals , Rats , Gastrointestinal Hormones/metabolism , Gonadotropin-Releasing Hormone/metabolism , Testosterone/blood , Testosterone/metabolism , Follicle Stimulating Hormone/blood , Follicle Stimulating Hormone/metabolism , Testis/metabolism , Testis/drug effects , Luteinizing Hormone/blood , Luteinizing Hormone/metabolism , Neuropeptides/metabolism , Neuropeptides/pharmacology , Hypothalamo-Hypophyseal System/metabolism , Hypothalamo-Hypophyseal System/drug effects , Infusions, Intraventricular , Hypothalamus/metabolism , Hypothalamus/drug effects , Sperm Count , Rats, Sprague-Dawley , Hypothalamic-Pituitary-Gonadal Axis
10.
Rev Int Androl ; 22(1): 17-22, 2024 Mar.
Article En | MEDLINE | ID: mdl-38735873

Obtaining sperm from the testis surgically and using these sperm with the intracytoplasmic sperm injection technique, has opened the way for the possibility of biological fathering in men with non-obstructive azoospermia (NOA). We aimed to evaluate our sperm retrieval rate (SRR) by microdissection testicular sperm extraction (micro-TESE) in NOA patients with solitary testis. In this retrospective case-control study, fortyfive patients with NOA who had a congenital or acquired solitary testis were included, between September 2003 and January 2022. These patients were randomly matched with patients with NOA who had bilateral testes, using a 1:3 matching ratio. We found that SRR by micro-TESE in patients with solitary testis was similar to NOA patients with bilateral testis (51.1% vs. 50.4%). Age, infertility period, ejaculate volume, serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone, history of varicocelectomy, history of orchiopexy, testicular stimulation therapy before micro-TESE, testicular volume, genetic status, TESE side, micro-TESE success, complications and histopathological evaluation results of both groups were evaluated, there was a statistically significant difference in only serum FSH and LH levels. There was no difference between the groups in terms of complications and hormonal effects in the early postoperative period. Micro-TESE in NOA patients with solitary testis has similar sperm retrieval and complication rates as NOA patients with bilateral testis.


Azoospermia , Microdissection , Sperm Retrieval , Testis , Humans , Male , Retrospective Studies , Microdissection/methods , Case-Control Studies , Adult , Testis/surgery , Sperm Injections, Intracytoplasmic/methods , Luteinizing Hormone/blood , Follicle Stimulating Hormone/blood
11.
BMC Psychiatry ; 24(1): 385, 2024 May 21.
Article En | MEDLINE | ID: mdl-38773397

BACKGROUND: Patients with bipolar disorder (BD) show abnormalities in glucolipid metabolism and reproductive hormone levels, which are of concern in women with BD. This study was dedicated to investigating the glucolipid and reproductive hormone levels of female patients, and to preliminarily investigating their relationships with cognition. METHODS: A total of 58 unmedicated female BD patients, 61 stable-medicated female BD patients, and 63 healthy controls (HC) were recruited in this study. Serum glycolipid indexes and reproductive hormones were measured. Cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Stroop Color-Word Test (Stroop test). RESULTS: Patients with BD showed significant cognitive impairment (p < 0.05), which was not affected by medication. Triglycerides (TG), luteinizing hormone (LH), and high-density lipoprotein cholesterol (HDL-c) were altered in stable-medicated BD patients. In addition, regression analysis showed that progesterone (PRGE) and prolactin (PRL) were negatively associated with cognitive performance in stable-medicated BD patients. CONCLUSIONS: Female BD patients may have cognitive deficits and abnormal levels of glycolipids and reproductive hormones. And abnormal levels of glycolipids and reproductive hormones may be associated with cognitive dysfunction in female BD patients.


Bipolar Disorder , Cognitive Dysfunction , Glycolipids , Humans , Female , Bipolar Disorder/blood , Bipolar Disorder/complications , Adult , Glycolipids/blood , Cognitive Dysfunction/blood , Cognitive Dysfunction/physiopathology , Luteinizing Hormone/blood , Prolactin/blood , Progesterone/blood , Triglycerides/blood , Cholesterol, HDL/blood , Middle Aged , Neuropsychological Tests/statistics & numerical data
12.
Sci Rep ; 14(1): 10190, 2024 05 03.
Article En | MEDLINE | ID: mdl-38702366

Dysfunction of central serotonergic neurons is known to cause depressive disorders in humans, who often show reproductive and/or glucose metabolism disorders. This study examined whether dorsal raphe (DR) serotonergic neurons sense high glucose availability to upregulate reproductive function via activating hypothalamic arcuate (ARC) kisspeptin neurons (= KNDy neurons), a dominant stimulator of gonadotropin-releasing hormone (GnRH)/gonadotropin pulses, using female rats and goats. RNA-seq and histological analysis revealed that stimulatory serotonin-2C receptor (5HT2CR) was mainly expressed in the KNDy neurons in female rats. The serotonergic reuptake inhibitor administration into the mediobasal hypothalamus (MBH), including the ARC, significantly blocked glucoprivic suppression of luteinizing hormone (LH) pulses and hyperglycemia induced by intravenous 2-deoxy-D-glucose (2DG) administration in female rats. A local infusion of glucose into the DR significantly increased in vivo serotonin release in the MBH and partly restored LH pulses and hyperglycemia in the 2DG-treated female rats. Furthermore, central administration of serotonin or a 5HT2CR agonist immediately evoked GnRH pulse generator activity, and central 5HT2CR antagonism blocked the serotonin-induced facilitation of GnRH pulse generator activity in ovariectomized goats. These results suggest that DR serotonergic neurons sense high glucose availability to reduce gluconeogenesis and upregulate reproductive function by activating GnRH/LH pulse generator activity in mammals.


Glucose , Goats , Gonadotropin-Releasing Hormone , Luteinizing Hormone , Receptor, Serotonin, 5-HT2C , Serotonergic Neurons , Animals , Luteinizing Hormone/metabolism , Female , Receptor, Serotonin, 5-HT2C/metabolism , Rats , Serotonergic Neurons/metabolism , Gonadotropin-Releasing Hormone/metabolism , Glucose/metabolism , Serotonin/metabolism , Kisspeptins/metabolism , Arcuate Nucleus of Hypothalamus/metabolism , Arcuate Nucleus of Hypothalamus/drug effects , Dorsal Raphe Nucleus/metabolism , Dorsal Raphe Nucleus/drug effects , Rats, Sprague-Dawley
13.
BMC Vet Res ; 20(1): 219, 2024 May 23.
Article En | MEDLINE | ID: mdl-38778406

The study aimed to assess the effects of water salinity on the sperm parameters, levels of cortisol, LH, FSH, testosterone and antioxidants as well as the testes' histopathology in Barki rams. Fifteen healthy Barki rams (1-1.5 years) were divided into three equal depending on the type of drinking water for nine months. The rams in the tap water group (TW, water that contained 350 ppm of total dissolved salts (TDS). Males in the high saline water group (HSW) were permitted to consume high saline water with 8,934 ppm TDS, whereas those in the second group were permitted to have moderately saline water (MSW, 4,557 ppm TDS). High salt concentration in drinking water had adverse effect on sperm viability, morphology and sperm cell concertation. Nitric oxide and malondialdehyde concentrations in blood were significantly higher in the MSW and HSW groups than in TW. There was a significant decrease in glutathione concentration as well as superoxide dismutase activity in TDS and HSW. Cortisol was most highly concentrated in the HSW, next in the MSW, and least in TW. The testosterone, LH, and FSH concentrations in the HSW and MSW groups were significantly lower than in TW. As the salt concentration in drinking water increases, damage to testicular tissue. The MSW group demonstrating vacuolation of lining epithelial cells with pyknotic nuclei in the epididymis and necrosis and desquamation of spermatogenic cells in seminiferous tubules while HSW group displaying desquamated necrotic cells and giant cell formation in the epididymis, as well as damage to some of the seminiferous tubules and showed congestion, vacuolation of spermatogenic epithelium of seminiferous tubules, and desquamated necrotic spermatogenic epithelium. In conclusion, the salinity of the water has detrimental impacts on the sperm morphology, viability and concentration, hormones and antioxidant levels in Barki rams.


Antioxidants , Spermatozoa , Testis , Testosterone , Male , Animals , Testis/drug effects , Testis/pathology , Antioxidants/metabolism , Spermatozoa/drug effects , Sheep , Testosterone/blood , Follicle Stimulating Hormone/blood , Hydrocortisone/blood , Saline Waters , Luteinizing Hormone/blood
14.
Sci Rep ; 14(1): 8229, 2024 04 08.
Article En | MEDLINE | ID: mdl-38589425

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting 5-20% of reproductive-age women. However, the treatment of PCOS is mainly based on symptoms and not on its pathophysiology. Neuroendocrine disturbance, as shown by an elevated LH/FSH ratio in PCOS patients, was thought to be the central mechanism of the syndrome, especially in lean PCOS. LH and FSH secretion are influenced by GnRH pulsatility of GnRH neurons in the hypothalamus. Kisspeptin is the main regulator of GnRH secretion, whereas neurokinin B (NKB) and dynorphin regulate kisspeptin secretion in KNDy neurons. This study aims to deepen the understanding of the neuroendocrine disorder in lean PCOS patients and its potential pathophysiology-based therapy. A cross-sectional study was performed at Dr. Cipto Mangunkusumo Kencana Hospital and the IMERI UI HRIFP cluster with 110 lean PCOS patients as subjects. LH, FSH, LH/FSH ratio, kisspeptin, NKB, dynorphin, leptin, adiponectin, AMH, fasting blood glucose, fasting insulin, HOMA-IR, testosterone, and SHBG were measured. Bivariate and path analyses were performed to determine the relationship between variables. There was a negative association between dynorphin and kisspeptin, while NKB levels were not associated with kisspeptin. There was no direct association between kisspeptin and the LH/FSH ratio; interestingly, dynorphin was positively associated with the LH/FSH ratio in both bivariate and pathway analyses. AMH was positively correlated with the LH/FSH ratio in both analyses. Path analysis showed an association between dynorphin and kisspeptin levels in lean PCOS, while NKB was not correlated with kisspeptin. Furthermore, there was a correlation between AMH and the LH/FSH ratio, but kisspeptin levels did not show a direct significant relationship with the LH/FSH ratio. HOMA-IR was negatively associated with adiponectin levels and positively associated with leptin and FAI levels. In conclusion, AMH positively correlates with FAI levels and is directly associated with the LH/FSH ratio, showing its important role in neuroendocrinology in lean PCOS. From the path analysis, AMH was also an intermediary variable between HOMA-IR and FAI with the LH/FSH ratio. Interestingly, this study found a direct positive correlation between dynorphin and the LH/FSH ratio, while no association between kisspeptin and the LH/FSH ratio was found. Further research is needed to investigate AMH and dynorphin as potential therapeutic targets in the management of lean PCOS patients.


Luteinizing Hormone , Polycystic Ovary Syndrome , Female , Humans , Dynorphins/metabolism , Leptin , Kisspeptins/metabolism , Cross-Sectional Studies , Adiponectin , Neurokinin B/metabolism , Gonadotropin-Releasing Hormone/metabolism , Follicle Stimulating Hormone
15.
Mol Reprod Dev ; 91(4): e23741, 2024 Apr.
Article En | MEDLINE | ID: mdl-38616716

Inflammatory damage in ovarian granulosa cells (GCs) is a key mechanism in polycystic ovary syndrome (PCOS), cytoplasmic polyadenylation element binding protein-1 (CPEB1) is important in inflammatory regulation, however, its role in PCOS is unclear. We aim to research the mechanism of CPEB1 in ovarian GCs in PCOS using dehydroepiandrosterone (DHEA)-induced PCOS rat models and testosterone-incubated GC models. The pathophysiology in PCOS rats was analyzed. Quantitative-realtime-PCR, TUNEL, immunohistochemistry, and Western blot were applied for quantification. Additionally, cell counting kit-8, flow cytometry, immunofluorescence, Western blot, and Monodansylcadaverine staining were performed. We found that PCOS rat models exhibited a disrupted estrus cycle, elevated serum levels of testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH), increased LH/FSH ratio, and heightened ovarian index. Furthermore, reduced corpus luteum and increased follicular cysts were observed in ovarian tissue. In ovarian tissue, autophagy and apoptosis were activated and CPEB1 was overexpressed. In vitro, CPEB1 overexpression inhibited cell viability and sirtuin-1 (SIRT1), activated tumor necrosis factor-α, and interleukin-6 levels, as well as apoptosis and autophagy; however, CPEB1 knockdown had the opposite effect. In conclusion, overexpression of CPEB1 activated autophagy and apoptosis of ovarian GCs in PCOS.


Polycystic Ovary Syndrome , Animals , Female , Rats , Apoptosis , Autophagy , Follicle Stimulating Hormone, Human , Granulosa Cells , Luteinizing Hormone , mRNA Cleavage and Polyadenylation Factors/genetics , Polycystic Ovary Syndrome/chemically induced , Testosterone , Transcription Factors
16.
Front Cell Infect Microbiol ; 14: 1364097, 2024.
Article En | MEDLINE | ID: mdl-38606298

Background: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disease in women, intricately linked to hormonal imbalances. The microbiota composition plays a pivotal role in influencing hormonal levels within the body. In this study, we utilized a murine model to investigate how intestinal and vaginal microbiota interact with hormones in the development of PCOS. Methods: Twenty female mice were randomly assigned to the normal group (N) and the model group (P), where the latter received daily subcutaneous injections of 0.1 mL DHEA (6 mg/100 g). Throughout the experiment, we evaluated the PCOS mouse model by estrus cycle, serum total testosterone (T), prolactin (PRL) and luteinizing hormone (LH) levels, and ovarian pathological morphology. The microbial composition in both intestinal content and vaginal microbiota were studied by 16S rRNA gene high-throughput sequencing. Results: Compared with the N group, the P group showed significant increases in body weight, T, and PRL, with significant decrease in LH. Ovaries exhibited polycystic changes, and the estrous cycle was disrupted. The intestinal microbiota result shows that Chao1, ACE, Shannon and Simpson indexes were decreased, Desulfobacterota and Acidobacteriota were increased, and Muribaculaceae, Limosilactobacillus and Lactobacillus were decreased in the P group. T was significantly positively correlated with Enterorhabdus, and LH was significantly positively correlated with Lactobacillus. The analysis of vaginal microbiota revealed no significant changes in Chao1, ACE, Shannon, and Simpson indices. However, there were increased in Firmicutes, Bacteroidota, Actinobacteriota, Streptococcus, and Muribaculaceae. Particularly, Rodentibacter displayed a robust negative correlation with other components of the vaginal microbiota. Conclusion: Therefore, the response of the intestinal microbiota to PCOS is more significant than that of the vaginal microbiota. The intestinal microbiota is likely involved in the development of PCOS through its participation in hormonal regulation.


Gastrointestinal Microbiome , Microbiota , Polycystic Ovary Syndrome , Humans , Female , Mice , Animals , Luteinizing Hormone , RNA, Ribosomal, 16S/genetics , Testosterone
17.
J Ovarian Res ; 17(1): 78, 2024 Apr 10.
Article En | MEDLINE | ID: mdl-38600539

BACKGROUND: This study investigated the association between Anti-Müllerian Hormone (AMH) and relevant metabolic parameters and assessed its predictive value in the clinical diagnosis of polycystic ovarian syndrome (PCOS). METHODS: A total of 421 women aged 20-37 years were allocated to the PCOS (n = 168) and control (n = 253) groups, and their metabolic and hormonal parameters were compared. Spearman correlation analysis was conducted to investigate associations, binary logistic regression was used to determine PCOS risk factors, and receiver operating characteristic (ROC) curves were generated to evaluate the predictive value of AMH in diagnosing PCOS. RESULTS: The PCOS group demonstrated significantly higher blood lipid, luteinizing hormone (LH), and AMH levels than the control group. Glucose and lipid metabolism and hormonal disorders in the PCOS group were more significant than in the control group among individuals with and without obesity. LH, TSTO, and AMH were identified as independent risk factors for PCOS. AMH along with LH, and antral follicle count demonstrated a high predictive value for diagnosing PCOS. CONCLUSION: AMH exhibited robust diagnostic use for identifying PCOS and could be considered a marker for screening PCOS to improve PCOS diagnostic accuracy. Attention should be paid to the effect of glucose and lipid metabolism on the hormonal and related parameters of PCOS populations.


Anti-Mullerian Hormone , Polycystic Ovary Syndrome , Female , Humans , Anti-Mullerian Hormone/blood , Glucose/metabolism , Luteinizing Hormone/blood , Polycystic Ovary Syndrome/blood , Polycystic Ovary Syndrome/metabolism , Polycystic Ovary Syndrome/pathology , Sensitivity and Specificity , Adult
18.
Rev Assoc Med Bras (1992) ; 70(3): e20230918, 2024.
Article En | MEDLINE | ID: mdl-38655994

OBJECTIVE: The objective of this study was to learn more about the prevalence and pathophysiology of depression and anxiety that may be caused by polycystic ovary syndrome and to make plans for taking necessary precautions for this vulnerable group. METHODS: This case-control study was conducted between January 2022 and October 2022. A total of 120 women with polycystic ovary syndrome and 143 controls were included in the study. All healthy volunteers and women with polycystic ovary syndrome were evaluated using self-administered questionnaires and physical examination. Anthropometric data such as weight and height and laboratory value were documented. RESULTS: There was no significant difference between the groups in terms of demographic characteristics. When the Hospital Anxiety and Depression Scale scores of both groups were compared, both depression and anxiety scores were found to be significantly higher in women with polycystic ovary syndrome compared with the control group (OR: 3.319, 95%CI, 1.563-7.047, p<0.001 and OR: 3.238, 95%CI, 1.659-6.315, p<0.001). In the Hospital Anxiety and Depression Scale questionnaire, the rate of irregular menstruation and Ferriman-Gallwey score were statistically significant in women with polycystic ovary syndrome with high depression and anxiety scores. While serum LH levels and LH/FSH ratios were significantly different in women with polycystic ovary syndrome with high depression scores, serum LH, LH:FSH ratios, and serum total testosterone levels were found significant in women with polycystic ovary syndrome with high anxiety scores. CONCLUSION: It is clear that depression and anxiety are more common in patients with polycystic ovary syndrome than in healthy women. Our findings support previous recommendations regarding routine screening for depression and anxiety in this population.


Anxiety , Depression , Polycystic Ovary Syndrome , Humans , Polycystic Ovary Syndrome/psychology , Polycystic Ovary Syndrome/complications , Polycystic Ovary Syndrome/blood , Female , Cross-Sectional Studies , Case-Control Studies , Adult , Risk Factors , Depression/epidemiology , Depression/etiology , Anxiety/etiology , Anxiety/epidemiology , Young Adult , Surveys and Questionnaires , Prevalence , Adolescent , Psychiatric Status Rating Scales , Luteinizing Hormone/blood
19.
Sci Rep ; 14(1): 8989, 2024 04 18.
Article En | MEDLINE | ID: mdl-38637687

In mammals reproduction is regulated by many factors, among others by the peptides belonging to the RFamide peptide family. However, the knowledge concerning on the impact of recently identified member of this family (QRFP43) on the modulation of the gonadotrophic axis activity is still not fully understood and current research results are ambiguous. In the present study we tested the in vivo effect of QRFP43 on the secretory activity of the gonadotrophic axis at the hypothalamic-pituitary level in Polish Merino sheep. The animals (n = 48) were randomly divided into three experimental groups: controls receiving an icv infusion of Ringer-Locke solution, group receiving icv infusion of QRFP43 at 10 µg per day and 50 µg per day. All sheep received four 50 min icv infusions at 30 min intervals, on each of three consecutive days. Hypothalamic and pituitaries were collected and secured for further immunohistochemical and molecular biological analysis. In addition, during the experiment a blood samples have been collected for subsequent RIA determinations. QRFP43 was found to downregulate Kiss mRNA expression in the MBH and reduce the level of IR material in ME. This resulted in a reduction of GnRH IR material in the ME. QRFP43 increased plasma FSH levels while decreasing LH levels. Our findings indicate that QRFP43 inhibits the activity of the gonadotropic axis in the ovine at the level of the hypothalamus and may represent another neuromodulator of reproductive processes in animals.


Gonadotrophs , Luteinizing Hormone , Female , Sheep , Animals , Gonadotropin-Releasing Hormone/metabolism , Hypothalamus/metabolism , Pituitary Gland/metabolism , Gonadotrophs/metabolism , Follicle Stimulating Hormone , Mammals/metabolism
20.
Endocrinol Metab Clin North Am ; 53(2): 217-227, 2024 Jun.
Article En | MEDLINE | ID: mdl-38677865

A thorough history and physical examination including Tanner staging and growth assessments can guide differential diagnosis and aid in the evaluation of precocious puberty. Basal luteinizing hormone levels measured using a highly sensitive assay can be helpful in diagnosing central precocious puberty (CPP). Brain MRI is indicated with males diagnosed with CPP and females under the age of 6 with CPP. As more information becomes available regarding the genetic etiologies of CPP, genetic testing may preclude the need for imaging studies and other hormonal testing, especially in familial cases.


Puberty, Precocious , Humans , Puberty, Precocious/diagnosis , Puberty, Precocious/blood , Male , Child , Female , Luteinizing Hormone/blood , Magnetic Resonance Imaging , Child, Preschool
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