Serum Follicle-stimulating Hormone Levels Research Articles

Change of the retinoic acid pathway in hypothalamus and pituitary damage induced by combined exposure to low-level Pb~(2+) and 1-nitropyrene in mice

To observe the expression of the retinoic acid(RA) pathway in hypothalamus and pituitary damage induced by combined exposure of low-level lead and 1-nitropyrene in mice, and to explore the relationship between the changes of RA pathway and hypothalamus and pituitary damage. A total of 84 4-week-old ICR mice were randomly divided into the control group, Pb~(2+) tainted group(0.008 mg/L), 1-NP tainted group(0.1 mg/kg), low(0.008 mg/L Pb~(2+)+0.004 mg/kg 1-NP), medium(0.008 mg/L Pb~(2+)+0.02 mg/kg 1-NP), and high-dose co-toxicity group(0.008 mg/L Pb~(2+)+0.1 mg/kg 1-NP) according to body weight, with 14 mice in each group. Among them, Pb~(2+) was provided by lead acetate, added to deionized water and ingested by mice drinking freely, 1-NP was given by intraperitoneal injection, 1-NP was administered by intraperitoneal injection. Record daily water intake and food intake. After 21 consecutive days of exposure, body mass was measured, histological changes in the hypothalamus and pituitary were observed under an optical microscope, and lead content in brain tissue was measured by atomic absorption spectrometry. The real-time fluorescence quantitative PCR was used to detect the abundance of retinoic acid pathway members and c-Jun N-terminal kinases genes(Jnks), and the western blot method was used to detect expression levels of acetaldehyde dehydrogenase 2(ALDH2), cytochrome P450 family member 26A1(CYP26a1) proteins. There was no difference in the mean weekly water intake and food intake of the mice in each group. The body weight of the high-dose co-toxicity group mice((27.4±1.9)g) was lower than that of the control group((29.8±2.3)g)(P<0.05). The level of serum follicle-stimulating hormone(FSH) in the middle and high dose co-toxicity groups((265.01±2.99), (260.42±3.61)pg/mL, respectively) was lower than that in the control group((279.00±1.30)pg/mL, P<0.05). The content of Pb~(2+) in the brain of each group containing Pb~(2+) was higher than that of the control group. In the hypothalamic and pituitary tissues, the abundance of Adh1, Adh2, Rar and Rxr, and ALDH2 levels in the medium and high dose co-toxicity groups were higher than those in the control group(P<0.05). Cyp26a1 gene abundance and protein levels were lower in the medium and high dose co-toxicity groups than in the control group(P<0.05). The abundance of Jnks in the high-dose co-toxicity group was higher than that in the control group(P<0.05). Continuous exposure to 0.008 mg/L Pb~(2+)+0.1 mg/kg 1-NP for 21 days can cause damage to the hypothalamus and pituitary of mice, and activate the RA signaling pathway.

Mechanism of protective effect of resveratrol on poor ovarian response in mice

This study aims to investigate the therapeutic effects and potential mechanisms of resveratrol(Res) on poor ovarian response(POR) in mice. The common target genes shared by Res and POR were predicted by network pharmacology, used for Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment, and then validated by animal experiments. The mice with regular estrous cycle after screening were randomized into normal, POR, and low-and high-dose(20 and 40 mg·kg~(-1), respectively) Res groups. The normal group was administrated with an equal volume of 0.9% sodium chloride solution by gavage, and the mice in other groups with tripterygium glycosides suspension(50 mg·kg~(-1)) by gavage for 2 weeks. After the modeling, the mice in low-and high-dose Res groups were treated with Res by gavage for 2 weeks, and the mice in normal and POR groups with an equal volume of 0.9% sodium chloride solution by gavage. Ovulation induction and sample collection were carried out on the day following the end of treatment. Vaginal smears were collected for observation of the changes in the estrous cycle, the counting of retrieved oocytes, and the measurement of ovarian wet weight and ovarian index. The enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of anti-mullerian hormone(AMH), follicle-stimulating hormone(FSH), estradiol(E_2), and luteinizing hormone(LH) in the serum. The ovarian tissue morphology and granulosa cell apoptosis were observed by hematoxylin-eosin(HE) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL), respectively. Western blot was employed to determine the protein levels of phosphatidylinositol 3-kinase(PI3K), protein kinase B(AKT), forkhead box O(FOXO) 3a, hypoxia-inducible factor(HIF)-1α, B-cell lymphoma-2(Bcl-2), and Bcl-2-associated X protein(Bax). A total of 222 common targets shared by Res and POR were collected. GO annotation indicated that these targets were mainly involved in oxidative stress response. KEGG enrichment analysis revealed that Res can intervene in POR via PI3K/AKT, HIF-1, and FOXO signaling pathways. Animal experiments showed that the model group had higher rate of estrous cycle disorders, lower number and poorer morphology of normally developed follicles at all levels, more atretic follicles, higher apoptosis of ovarian granulosa cells, lower number of retrieved oocytes, lower ovarian wet weight and ovarian index, higher serum levels of FSH and LH, lower levels of AMH and E_2, higher expression levels of HIF-1α, FOXO3a and Bax, and lower expression levels of PI3K, AKT, and Bcl-2 in the ovarian tissue than the normal group. Compared with the POR group, low-and high-dose Res decreased the rate of estrous cycle disorders, improved the follicle number and morphology, reduced atretic follicles, promoted the apoptosis of ovarian granulosa cells, increased retrieved oocytes, ovarian wet weight and ovarian index, and lowered serum FSH and LH levels. Moreover, Res down-regulated the expression levels of HIF-1α, FOXO3a and Bax, and up-regulated the expression levels of PI3K, AKT and Bcl-2 in the ovarian tissue. In summary, Res can inhibit apoptosis and mitigate poor ovarian response in mice by regulating the PI3K/AKT/FOXO3a and HIF-1α pathways.

Gonadotropins in the Management of Couple Infertility: Toward the Rational Use of an Empirical Therapy.

Although epidemiology shows that both men and woman can experience infertility, the female partner usually experiences most of the diagnostic and therapeutic burden. Thus, management of couple infertility is a unique example of gender inequality. The use of exogenous gonadotropins in assisted reproductive technology (ART) to induce multifollicular growth is well consolidated in women, but the same is not done with the same level of confidence and purpose in infertile men. Indeed, the treatment of idiopathic male infertility is based on an empirical approach that involves administration of the follicle-stimulating hormone (FSH) in dosages within the replacement therapy range. This treatment has so far been attempted when the endogenous FSH serum levels are within the reference ranges. According to the most recent evidence, a "substitutive" FSH administration may not be effective enough, while a stimulatory approach could boost spermatogenesis over its basal levels without adverse extragonadal effects. This article aims to describe the rationale behind the empirical application of gonadotropins in couple infertility, highlighting the need for a change in the therapeutic approach, especially for the male partner.

Impact of coenzyme Q10 as an adjuvant therapy to letrozole on spermiogram results and sex hormone levels in Iraqi men with infertility; randomized open label comparative study

Background: Worldwide, infertility affects about 15% of reproductive-age couples. In many cases, infertility can't be treated, however new treatment options with promising value have been involved in recent clinical trials. The aim of this clinical trial was to evaluate the impacts of adding coenzyme Q10 (CoQ10) to letrozole on the results of spermiogram and sex hormone tests in men diagnosed with idiopathic oligoasthenoteratozoospermia (iOAT) syndrome, which is a type of male defective spermatogenesis of unknown etiology. Methods: This randomized, open-label, parallel two-arm interventional study included 67 adult male patients aged 18-60 years with a confirmed diagnosis of iOAT syndrome recruited from The High Institute for Infertility Diagnosis & Assisted Reproduction Technologies/Nahrain University. Patients were randomly separated into two groups, Group A included 29 patients treated with letrozole 2.5 mg tablet orally twice a week, Group B included 38 patients treated with a combination of letrozole 2.5 mg tablet orally twice a week plus CoQ10 400 mg per day. Both groups completed treatment for three months. Semen samples, serum follicle-stimulating hormone (FSH), estradiol (E2), and testosterone (T) were analyzed at day one, and at the end of month one, two and three. Results: Both groups showed that sperm concentration, normal morphology, total sperm count and motility, serum testosterone and FSH levels, and T/E2 ratio were significantly increased, while estradiol levels significantly decreased after three months of treatment. Seminal fluid volume changed significantly in group A only. In comparing between the two groups, all measured parameters, apart from sperm motility and FSH level, demonstrated a significant difference after three months of treatment, while sperm volume reached significant value after only two months of therapy. Conclusions: CoQ10 as adjuvant treatment to letrozole effectively improved most of the tested sperm parameters in Iraqi men with iOAT. Registration: ClinicalTrials.gov (NCT05847257, May 6, 2023).

Single versus intermittent cycle exposure effect of 6-mercaptopurine in juvenile Sprague-Dawley rat: a germ cell-specific mechanistic study.

Infertility is a frequent long-term adverse effect of cancer therapy for children. Compromised testicular functions in adolescence are frequent observations after chemotherapy and there are currently no well-established alternatives to avoid this damage. Antimetabolites such as 6-mercaptopurine (6-MP) are used to treat a variety of cancer; however, its treatment-associated adverse effects on the male reproductive functions are overlooked. Here, the molecular processes underlying 6-MP-induced male germ cell damage in juvenile Sprague-Dawley (SD) rats (3weeks) have been investigated. Rats were administered with low (5mg/kg), medium (10mg/kg), and high (20mg/kg) doses of 6-MP per orally either singly (1week × 1 cycle) or intermittently (1week treatment followed by 1week remission period × 3 cycles). The toxicity was evaluated in terms of genotoxicity and testes- and sperm-related cellular and molecular parameters. Single cycle of exposure either produced mild or no toxic manifestations at the end of the 6th week. Intermittent cycles of exposure, particularly at the 10 and 20mg/kg, decreased body and organ weights, increased micronucleated cells in the peripheral blood, induced oxidative/nitrosative stress, altered sperm chromatin quality, reduced serum testosterone and follicle stimulating hormone (FSH) levels, increased testicular structural aberrations, DNA damage, and apoptosis, and upregulated TNF-α expression and downregulated p-AMPK and β-catenin expressions. Conclusively, intermittent cycles of exposure at 10 and 20mg/kg doses to the juvenile rats significantly induced oxidative stress, genotoxicity, and cellular and molecular perturbations in the testes and sperm of adult rats.

Comparison of testosterone, FSH, LH and E2 hormone levels in infertility suspected males with COVID-19 infection.

Coronavirus disease 2019 (COVID-19) is an infectious disease that has many adverse impacts on many systems including reproduction. The direct effects of COVID-19 on urogenital system are still open to argue. This study aimed to compare testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) hormone levels in COVID-19 infected male individuals with infertility suspicion. One hundred five control (healthy) and 105 COVID-19 infected males aged between 20 to 54 years old were enrolled in the study. All patients were either diagnosed with primary or secondary infertility suspicion. The COVID-19 infection was diagnosed via reverse-transcription polymerase chain reaction test. Blood samples from patients were analyzed from the control and COVID-19 group to measure serum testosterone, FSH, LH, and E2 levels. Hormone levels were statistically compared between groups with the Independent T test. In control and COVID-19 patients, no significance was determined for FSH and LH hormone values. Testosterone hormone were significantly decreased and E2 level was statistically increased in COVID-19 patients compared to that in the control group (P < .001). COVID-19 is a viral disease that affects organ including gonads. COVID-19 infection decreased testosterone levels and increased E2 levels, which leading to disorders in male and female reproductivity.

Pinostrobin, a dietary bioflavonoid exerts antioxidant, anti-inflammatory, and anti-apoptotic protective effects against methotrexate-induced ovarian toxicity in rats

This study investigated the protective activities of pinostrobin (PIN) against methotrexate (MTX)-induced ovarian toxicity. Female rats were administered with PIN (50 mg/kg) for 4 weeks, while MTX was administered from weeks 2–4 of PIN treatment. Serum hormonal profiles, ovarian oxidative stress, inflammatory and apoptotic biomarkers as well as ovarian histomorphometry were evaluated. MTX administration elicited profound deficit in serum progesterone and estrogen (E2) levels, while luteinizing hormone (LH) and follicle stimulating hormone (FSH) were significantly increased. Additionally, MTX administration was associated with significant increases in ovarian malondialdehyde, nitric oxide, NF-кB, TNF-α, IL-6, IL-1β, iNOS and caspase-3 activity, as well as notable reduction in the activities of glutathione peroxidase, catalase and superoxide dismutase as well as the level of glutathione. Whereas, treatment with PIN significantly decreased serum levels of FSH and LH, as well as ovarian levels of NO, MDA, caspase 3, NF-κB, IL-1β, IL-6, TNF-α and iNOS. PIN also significantly upregulated GSH, GPx, CAT and SOD in the ovarian tissues as well as increased serum E2 and progesterone levels compared to the MTX group. Furthermore, PIN significantly restored altered ovarian histoarchitecture in the treated group. These findings suggests that PIN exerts protective effects against MTX-triggered ovarian damages.

The effects of short-term and long-term phthalate exposures on ovarian follicle growth dynamics and hormone levels in female mice†.

Di(2-ethylhexyl) phthalate and diisononyl phthalate are widely used as plasticizers in polyvinyl chloride products. Short-term exposures to phthalates affect hormone levels, ovarian follicle populations, and ovarian gene expression. However, limited data exist regarding the effects of long-term exposure to phthalates on reproductive functions. Thus, this study tested the hypothesis that short-term and long-term exposure to di(2-ethylhexyl) phthalate or diisononyl phthalate disrupts follicle dynamics, ovarian and pituitary gene expression, and hormone levels in female mice. Adult CD-1 female mice were exposed to vehicle, di(2-ethylhexyl) phthalate, or diisononyl phthalate (0.15ppm, 1.5ppm, or 1500ppm) via the chow for 1 or 6months. Short-term exposure to di(2-ethylhexyl) phthalate (0.15ppm) and diisononyl phthalate (1.5ppm) decreased serum follicle-stimulating hormone levels compared to control. Long-term exposure to di(2-ethylhexyl) phthalate and diisononyl phthalate (1500 ppm) increased the percentage of primordial follicles and decreased the percentages of preantral and antral follicles compared to control. Both phthalates increased follicle-stimulating hormone levels (di(2-ethylhexyl) phthalate at 1500ppm; diisononyl phthalate at 1.5ppm) and decreased luteinizing hormone levels (di(2-ethylhexyl) phthalate at 0.15 and 1.5ppm; diisononyl phthalate at 1.5ppm and 1500ppm) compared to control. Furthermore, both phthalates altered the expression of pituitary gonadotropin subunit genes (Cga, Fshb, and Lhb) and a transcription factor (Nr5a1) that regulates gonadotropin synthesis. These data indicate that long-term exposure to di(2-ethylhexyl) phthalate and diisononyl phthalate alters follicle growth dynamics in the ovary and the expression of gonadotropin subunit genes in the pituitary and consequently luteinizing hormone and follicle-stimulating hormone synthesis.

FRI283 Fragile X Gene Mutations Alter GnRH Neuron And Ovarian Innervation With Consequences On Reproductive Function

Abstract Disclosure: P.A. Villa: None. N. Lainez: None. C.R. Jonak: None. S. Berlin: None. I. Ethell: None. D. Coss: None. Mutations in the Fragile X messenger ribonucleoprotein 1 gene (FMR1) cause Fragile X syndrome, the most common cause of inherited mental disability, attributed to the loss of the Fragile X messenger ribonucleoprotein (FMRP). FMR1 mutations also comprise a majority of the genetic causes of premature ovarian failure (POF) in women, mechanisms of which are unknown. We utilized the Fmr1KO mouse model to determine the role of the FMR1 gene in the reproductive system in females. Similarly to what occurs in women harboring the mutation, our data demonstrate that Fmr1KO female mice experienced premature reproductive senescence, where reproductive function stopped at p163; in contrast, wild type controls stopped reproducing at p263. Since POF in women can occur due to either an insufficient pool of primordial follicles or early depletion of follicles, we quantified primordial follicles in 3 week old females and determined there was no difference between KO and controls. We then determined that Fmr1KO females had a higher number of corpora lutea at 8 weeks of age and gave birth to larger litters, suggesting that KO females recruit more follicles in each estrus cycle. Given that follicle stimulating hormone (FSH) and luteinizing hormone (LH) are essential in ovarian function, we analyzed gonadotropin levels in Fmr1KO females and determined they have higher serum LH and FSH. Inhibin b, progesterone, and testosterone levels were also higher, suggesting that high gonadotropins do not result from the lack of feedback. Ovariectomy determined that the hypothalamus drives high LH in KO females, while increased FSH is dependent on the ovaries. Increased vasculature in the corpora lutea and higher sympathetic innervation of developing follicles may increase steroid hormone production and drive increased serum FSH levels. To investigate the hypothalamic role in increased LH, we determined that a majority of gonadotropin-releasing hormone (GnRH) neurons express FMRP, which also have a higher number of GABAergic synapses in Fmr1KO females. Given that GABA is excitatory to GnRH neurons, alterations in afferent synaptic input can affect GnRH and LH secretion. LH pulsatile analysis determined higher LH pulse frequency in both unmodified and ovariectomized females, indicating an increase in GnRH neuron activity. In summary, our results reveal hypothalamic and ovarian contributions to the reproductive phenotype of Fragile X mutation carriers that may lead to early menopause. Presentation: Friday, June 16, 2023

Predictive role of 17α-hydroxy-progesterone serum levels of response to follicle-stimulating hormone in patients with abnormal sperm parameters

To study the possible role of serum 17α-hydroxy-progesterone (17αOH-P) levels in predicting favorable responses to follicle-stimulating hormone (FSH) administration in patients with normal serum FSH levels and idiopathic abnormal sperm parameters. Prospective cohort study. University-affiliated fertility center. Fifty patients with oligozoospermia, asthenozoospermia, and/or teratozoospermia and normal serum levels of gonadotropins and total testosterone (TT). Treatment with exogenous FSH is administered subcutaneously at a dose of 150 IU 3 times a week for 3 consecutive months. Luteinizing hormone levels, FSH levels, TT levels, 17αOH-P levels, testicular volume, conventional sperm parameters, and seminal spermatid concentration were evaluated before and after therapy. To evaluate the predictive role of pretreatment serum 17αOH-P levels on FSH responsiveness, the doubling of sperm concentration at the end of the FSH administration was considered a positive outcome. After therapy, patients showed a significant increase in sperm concentration, total sperm count (TSC), progressive motility, percentage of normal forms, FSH levels, TT levels, and testicular volume. There was a negative correlation between pretreatment 17αOH-P levels and the posttreatment increase in sperm concentration, TSC, progressive motility, and normal morphology, and a positive correlation with the posttreatment increase in spermatids. Predictive analysis showed that 17αOH-P levels (<1.18 ng/mL) foretold a doubling of sperm concentration with a sensitivity of 90.0% and a specificity of 73.3%, and of TSC with a sensitivity of 91.3% and a specificity of 81.48%. The results of this study suggest that pretreatment serum levels of 17αOH-P, a marker of steroidogenic function, appear to be able to predict the success of subcutaneous administration of exogenous FSH in terms of spermatogenesis improvement. Receiver operating characteristic curves indicated that 17αOH-P levels (<1.18 ng/mL) predict a doubling of sperm concentration and TSC after exogenous FSH administration to patients with idiopathic abnormal sperm parameters and normal gonadotropin levels.

Seminal TEX101 May Predict Seminal Sperm Recovery after Varicocelectomy in Nonobstructive Azoospermic Patients with Varicocele

Background. Infertile men with nonobstructive azoospermia (NOA) associated with varicocele may benefit from varicocele repair with recovered sperms in semen. Currently, there is no clinically applied method to predict the success of seminal sperm recovery in this subset of azoospermic men. Objective. We aimed to evaluate the predictive role of the seminal testis expressed protein (TEX101) in sperm recovery in the semen of NOA men with palpable bilateral varicocele after microsurgical varicocelectomy. Patients and Methods. This prospective cross-sectional cohort study included 40 patients with NOA and bilateral varicocele. Seminal TEX101 levels were measured followed by subinguinal microsurgical varicocele repair. Two seminal analyses were carried out at 3- and 6-month follow-up periods to evaluate seminal sperm recovery. Results. After varicocele repair, sperms were recovered in the semen of 10/40 patients (25%) along the follow-up periods (seven patients after 3 months and additional three patients after 6 months). The preoperative median seminal TEX101 level was significantly higher in NOA men with seminal sperm recovery compared with NOA patients without seminal sperm recovery (13.5 vs. 9.8 ng/ml, p = 0.014 ). Besides, the serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) median levels were significantly higher in NOA men without seminal sperm recovery compared with NOA men with seminal sperm recovery ( p = 0.001 , p = 0.01 ). There were nonsignificant differences comparing the preoperative testicular volume or serum testosterone levels between the two investigated groups ( p = 0.072 , p = 0.272 ). A cutoff value of 9.9 ng/ml was demonstrated to have preoperative TEX101 prediction of seminal sperm recovery (sensitivity of 90% and specificity of 57%). Conclusion. Preoperative seminal TEX101 could be considered as a biomarker for sperm recovery for seminal sperm recovery in NOA cases associated with varicocele after its surgical repair. Further work at this point with larger number of cases should be carried out to verify its potential importance.

Sex steroid hormones and allergic diseases in children: a pilot birth cohort study in the Japan Environment and Children’s Study cohort

BackgroundNumerous studies suggest that sex steroids might play a role in sex disparity observed in allergic diseases in adults. However, whether sex hormones influence allergic diseases in children remains unclear. The aim of the present study was to examine the association of sex steroid hormones with allergic disease in Japanese children.MethodsThe present cross-sectional study included 145 6-year-old children participating in a pilot birth cohort study in the Japan Environment and Children’s Study. Data on allergic diseases were obtained from questionnaires, and serum levels of sex steroid hormones and allergen-specific IgE were measured. Logistic regression was performed to evaluate the association of sex hormones with allergic diseases.ResultsAfter adjusted sex, amount of body fat at 6 years, parental history of allergic disease, and exposure to tobacco smoke, serum dehydroepiandrosterone sulfate level was significantly associated with reduced odds of any allergic disease (adjusted odds ratio, 0.58; 95% confidence interval, 0.36–0.93; P = 0.024) and serum follicle-stimulating hormone level was significantly associated with increased odds of any allergic disease (adjusted odds ratio, 2.04; 95% confidence interval, 1.01–4.11, P = 0.046). Dehydroepiandrosterone sulfate level showed a significant association with number of allergic diseases.ConclusionsThe current study findings suggest that sex hormones may play an important role in the development of allergic diseases in prepubertal children.

The predictive effect of serum AMH and FSH levels alone or in combination on fertility outcome

Objective: To explore the roles of anti-mullerian hormone (AMH) and follicle stimulating hormone (FSH) in predicting clinical pregnancy. Materials and Methods: Forty patients who were decided on IVF/ICSI due to different infertility etiologies were included in the study. The patients were divided into two groups according to their AMH and FSH values as having a good prognosis or a poor prognosis. The clinical pregnancy and miscarriage rates of 33 cycles with good prognosis and 17 cycles with poor prognosis were compared. Results: In the good prognosis group, the FSH value was significantly lower than the poor prognosis group (5.98±1.04 mIU/mL vs. 13.6±3.07 mIU/mL, p&lt;0.01), while the serum AMH level was significantly higher. (3.80±1.32 ng/mL vs 0.54±0.02 ng/mL, p&lt;0.01). The rate of chemical pregnancy in the group with good prognosis was twice as high and significant compared to the group with poor prognosis (12 (36.3%) vs 5 (29.4%), p&lt;0.02). In terms of clinical pregnancy rates, the group with good prognosis showed a higher frequency (33.3% vs. 23.5%, p&lt;0.001), while miscarraige rates were higher in the group with poor prognosis (9.0% vs. 25%, p&lt;0.003). Conclusions: Evaluation of AMH and FSH together is critical in determining clinical pregnancy rates.

Impact of coenzyme Q10 as an adjuvant therapy to letrozole on spermiogram results and sex hormone levels in Iraqi men with infertility; randomized open label comparative study

Background: Worldwide, infertility affects about 15% of reproductive-age couples. In many cases, infertility can't be treated, however new treatment options with promising value have been involved in recent clinical trials. The aim of this clinical trial was to evaluate the impacts of adding coenzyme Q10 (CoQ10) to letrozole on the results of spermiogram and sex hormone tests in men diagnosed with idiopathic oligoasthenoteratozoospermia (iOAT) syndrome, which is a type of male defective spermatogenesis of unknown etiology. Methods: This randomized, open-label, parallel two-arm interventional study included 67 adult male patients aged 18-60 years with a confirmed diagnosis of iOAT syndrome recruited from The High Institute for Infertility Diagnosis &amp; Assisted Reproduction Technologies/Nahrain University. Patients were randomly separated into two groups, Group A included 29 patients treated with letrozole 2.5 mg tablet orally twice a week, Group B included 38 patients treated with a combination of letrozole 2.5 mg tablet orally twice a week plus CoQ10 400 mg per day. Both groups completed treatment for three months. Semen samples, serum follicle-stimulating hormone (FSH), estradiol (E2), and testosterone (T) were analyzed at day one, and at the end of month one, two and three. Results: Both groups showed that sperm concentration, normal morphology, total sperm count and motility, serum testosterone and FSH levels, and T/E2 ratio were significantly increased, while estradiol levels significantly decreased after three months of treatment. Seminal fluid volume changed significantly in group A only. In comparing between the two groups, all measured parameters, apart from sperm motility and FSH level, demonstrated a significant difference after three months of treatment, while sperm volume reached significant value after only two months of therapy. Conclusions: CoQ10 as adjuvant treatment to letrozole effectively improved most of the tested sperm parameters in Iraqi men with iOAT. Registration: ClinicalTrials.gov (NCT05847257, May 6, 2023).

Ovarian reserve in children with juvenile idiopathic arthritis using biologic disease-modifying anti-rheumatic drugs.

The aim of the study is to assess the effect of juvenile idiopathic arthritis (JIA) and biologic disease-modifying anti-rheumatic drugs (bDMARDs) on ovarian reserve in children. A cross-sectional study was performed from March 2021 to March 2022 and included 81 patients with JIA and 49 healthy children. Serum anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol levels were analyzed using electrochemiluminescence methods. The mean of current age (13.5 ± 3.2 vs. 14.4 ± 2.4years), height standard deviation score (SDS) (- 0.35 ± 1.18 vs. - 0.44 ± 0.94), body mass index SDS (0.12 ± 1.33 vs. 0.25 ± 1.28), and the median weight SDS (- 0.13 (- 2.27-3.23) vs. - 0.52 (- 3.4-3.3)) were similar in JIA patients and controls (p > 0.05). Patients with JIA were divided into two groups according to their treatment regimens: treated with methotrexate (MTX) (biologic naive) (n = 32) and treated with MTX plus bDMARDs (n = 49). No significant differences were detected between the 3 groups regarding menarche age, menstrual cycle length, and flow duration (for all p > 0.05). The median serum concentration of AMH was 2.94 (1.12-7.88) ng/ml in the control group, 3.02 (0.36-8.54) ng/ml in the biologic naïve group, and 3.01 (0.99-8.26) ng/ml in the MTX plus bDMARD group. There were no significant differences between 3 groups according to serum AMH, FSH, LH, and estradiol levels (p > 0.05). Biologic DMARDs are reassuring in terms of ovarian reserve in girls with JIA and demonstrate that AMH is unaffected by treatment. Prospective studies with larger sample sizes are needed to confirm our findings and to evaluate the impact on the future fertility of patients. Key Points • Although biologic disease-modifying anti-rheumatic drugs (bDMARDs) are being game-changing treatment options in juvenile idiopathic arthritis, their effect on fertility and ovarian reserve is one of the most discussed issues. • In addition to treatment used, autoimmune diseases might also have a negative effect on fertility. • In this cross-sectional study, we found that anti-Mullerian hormone level of patients who were on bDMARDs, patients who were on methotrexate, and healthy controls were similar. • Our results suggest that bDMARDs are reassuring in terms of ovarian reserve in girls with JIA and demonstrate that AMH is unaffected by treatment.

Switching from high-fat diet to normal diet ameliorate BTB integrity and improve fertility potential in obese male mice

Obesity is a prominent risk factor for male infertility, and a high-fat diet is an important cause of obesity. Therefore, diet control can reduce body weight and regulate blood glucose and lipids, but it remains unclear whether it can improve male fertility and its mechanism. This study explores the effects of switching from a high-fat diet (HFD) to a normal diet (ND) on the fertility potential of obese male mice and its related mechanisms. In our study, male mice were separated into three groups: normal diet group (NN), continuous high-fat diet group (HH), and return to normal diet group (HN). The reproductive potential of mice was tested through cohabitation. Enzymatic methods and ELISA assays were used to measure metabolic indicators, follicle-stimulating hormone (FSH) levels and intratesticular testosterone levels. Transmission electron microscopy and immunofluorescence with biotin tracers assessed the integrity of the blood-testis barrier (BTB). Malondialdehyde (MDA), superoxide dismutase (SOD), and reactive oxygen species (ROS) were inspected for the assessment of oxidative stress. The expression and localization of BTB-related proteins were detected through the immunoblot and immunofluorescence. The mice in the high-fat diet group indicated increased body weight and epididymal fat weight, elevated serum TC, HDL, LDL, and glucose, decreased serum FSH, and dramatic lipid deposition in the testicular interstitium. Analysis of fertility potential revealed that the fertility rate of female mice and the number of pups per litter in the HH group were significantly reduced. After the fat intake was controlled by switching to a normal diet, body weight and epididymal fat weight were significantly reduced, serum glucose and lipid levels were lowered, serum FSH level was elevated and the deposition of interstitial lipids in the testicles was also decreased. Most significantly, the number of offspring of male mice returning to a normal diet was significantly increased. Following further mechanistic analysis, the mice in the sustained high-fat diet group had disrupted testicular BTB integrity, elevated levels of oxidative stress, and abnormal expression of BTB-related proteins, whereas the restoration of the normal diet significantly ameliorated the above indicators in the mice. Our study confirms diet control by switching from a high-fat diet to a normal diet can effectively reduce body weight, ameliorate testicular lipotoxicity and BTB integrity in male mice, and improve fertility potential, providing an effective treatment option for obese male infertility.

Elevated circulating follicle stimulating hormone level is associated with dyslipidemia in male type 2 diabetes mellitus patients: A cross-sectional study.

Type 2 diabetes mellitus (T2DM) commonly combines with dyslipidemia, and both are known as the risk factors of cardiovascular events and aggravate the arteriosclerosis progression. In this study, we investigated the relationship between follicle-stimulating hormone (FSH) and lipid profiles in male T2DM patients. We collected clinical data of male T2DM patients in the Chinese Han population hospitalised from January 2018 to June 2020. A total of 963 patients with a mean age of 58.89±12.25years old were enroled in this study. The results showed that the levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL)-C levels were decreased gradually from the highest quartile groups (Q4) to Q1 group relevant to luteinising hormone and FSH, and no significant difference was observed in high-density lipoprotein-C levels among Q4-Q1 groups. Sub-groups analysis showed that, with the increased FSH level, TC, TG, and LDL-C levels were increased in the elder group (40-59years old) than those in the younger group (20-39years old). Spearman's analysis revealed a positive correlation between FSH and the levels of TC, TG, and LDL-C (r=0.354, r=0.336, r=0.312, p<0.001, respectively). The effect of FSH is independent of the changes in total testosterone level. Multivariate analysis found that increased FSH levels (≥9.26mIU/mL) and decreased total testosterone levels (<13.30nmol/L) were positively correlated with high TC, TG, and LDL-Cemia (OR=4.014, 1.565, 1.602, 1.660, 2.127, 1.322, respectively, p<0.05). Our data suggest that high serum FSH level in male T2DM patients could be a potential independent risk factor correlated with the elevated TC, TG, and LDL-C.

Obesity May Impairs Mice Testicular Structure by STAT3/CYP19A1/Testosterone

Obesity is an increasing serious global public health issue and a risk factor for male infertility. Aromatase expression level is elevated in obese men, and this high level is as-sociated with diminished serum testosterone levels. We explored the underlying mechanism of infertility in obese men. Genome-wide association study datasets were used to predict the causal relationship between obesity and male infertility. An obese male mouse model was generated by feeding mice a high-fat diet while control model was generated by feeding mice a normal chow diet. Serum indicators including free fatty acids, insulin, Follicle-stimulating hormone, and testosterone were measured using ELISA, and impaired fertility in mice was demonstrated using immunohistochemistry. The expression levels of STAT3 and CYP19A1 were measured by RT-qPCR and western blotting, respectively. Simultaneous bioinformatics analysis of publicly available data was performed using the R programming language and JASPAR database. Obesity might lead to male infertility from a genomic perspective. Obese mice displayed reduced serum testosterone and follicle stimulating hormone levels along with structural abnormalities, ectopic lipid deposition, and chronic inflammation in the testes. Upregulation of STAT3/CYP19A1 expression in obese mice was linked to reduced serum testosterone levels and impaired fertility. Our observation may support the hypothesis that since the elevation of STAT3 expression in obesity, the promoted expressed CYP19A1 could increase a shift from testosterone to estrogens. The persistently elevated level of estrogen will further stimulate STAT3, which may constitute a positive feedback loop. These findings provide new insights into the mechanisms of obesity-mediated male fertility impairment.

Exploring Independent Effects of Follicle-Stimulating Hormone In Vivo in a Mouse Model.

During the transition from a reproductive to a nonreproductive phase (menopause), many women experience significant physiological and pathological changes, including decreased bone mass, increased blood lipids, and increased visceral adiposity. Levels of follicle-stimulating hormone (FSH) rise during the menopausal transition. Many studies have shown that FSH in various extragonadal tissues and organs is associated with the pathogenesis of multiple diseases. Thus, building an animal model that can help study the independent effects of FSH in vivo is particularly important. In this study, C57BL/6 female mice were ovariectomized and supplemented with estradiol valerate (OVX + E2) to eliminate the effect of the hypothalamic-pituitary-gonadal axis. The OVX + E2 mice received solvent (N.S.) or different doses of recombinant FSH via intraperitoneal injection to create a mouse model (OVF) characterized by relatively stable estrogen and rising FSH levels. Thus, we successfully generated an experimental mouse model to mimic the early stage of menopause transition, characterized by elevated serum FSH levels. The OVF model has the advantages of being stable, low cost, and easy to operate, which is suitable for studies to explore the extragonadal actions of FSH. Here, we describe detailed protocols for the mouse OVF model.

Follicle-stimulating hormone is negatively associated with nonalcoholic fatty liver disease in a Chinese elderly population: a retrospective observational study

BackgroundSeveral studies have explored the connection between follicle-stimulating hormone (FSH) and nonalcoholic fatty liver disease (NAFLD). However, the impact of FSH elevation on NAFLD remains a topic of debate. Hence, this investigation aimed to evaluate the potential correlation between FSH levels and NAFLD in the aging population.MethodsThis was a retrospective observational cross-sectional study between July 2017 and August 2018 in our hospital. We used data obtained from 455 patients over 60 years old. Anthropometrics and laboratory tests were performed for each patient. NAFLD was diagnosed by sonographic features and the fatty liver index (LFI).ResultsOf the 455 patients, 200 (43.96%) had NAFLD on their ultrasound and 169 (37.14%) had NAFLD according to the LFI. An intraclass correlation coefficient of the two methods was 80.4% (P < 0.001). People with NAFLD on their ultrasound showed lower FSH levels (52.68 vs. 61.39 IU/L) and more unfavorable metabolic profiles. FSH was negatively correlated with age, alanine aminotransferase, estradiol, testosterone, systolic blood pressure, waist, body mass index, fasting blood glucose, postload plasma glucose and positive associated with total cholesterol, high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol by Spearman correlation analysis (all P < 0.05). By controlling for all confounding factors, the odds ratios (OR) of FSH for NAFLD were determined in elderly individuals, both men and women, aged 60–70 years and over 70 years. These ORs were found to be 0.937, 0.982, 0.983, and 0.973, respectively, with corresponding 95% confidence intervals (CI) of 0.892–0.984 (P = 0.009), 0.971–0.993 (P = 0.002), 0.967–0.999 (P = 0.033), and 0.958–0.989 (P = 0.001). In addition, our findings demonstrated no significant correlation between FSH and advanced fibrosis when adjusting for potential covariates. The OR for advanced fibrosis was 0.979 (95% CI, 0.938–1.022, P = 0.339). Additionally, ROC curve analysis showed an optimal cut-off value of 66.91 for women and 15.25 for men for NAFLD diagnosis.ConclusionsThere was an inverse relationship observed between levels of FSH in the blood serum and NAFLD in the elderly population. These findings suggest that reduced FSH levels might serve as a potential risk factor or biomarker for NAFLD in the elderly.