Serum Gonadotropin Research Articles

Low-Dose Estrogens as Neuroendocrine Modulators in Functional Hypothalamic Amenorrhea (FHA): The Putative Triggering of the Positive Feedback Mechanism(s).

Functional hypothalamic amenorrhea (FHA) is a non-organic reversible chronic endocrine disorder characterized by an impaired pulsatile secretion of the gonadotropin-releasing hormone (GnRH) from the hypothalamus. This impaired secretion, triggered by psychosocial and metabolic stressors, leads to an abnormal pituitary production of gonadotropins. As LH and FSH release is defective, the ovarian function is steadily reduced, inducing a systemic hypoestrogenic condition characterized by amenorrhea, vaginal atrophy, mood changes and increased risk of osteoporosis and cardiovascular disease. Diagnosis of FHA is made excluding other possible causes for secondary amenorrhea, and it is based upon the findings of low serum gonadotropins and estradiol (E2) with evidence of precipitating factors (excessive exercise, low weight, stress). Treatments of women with FHA include weight gain through an appropriate diet and physical activity reduction, psychological support, and integrative approach up to estrogen replacement therapy. If no spontaneous ovarian function is restored, assisted reproductive technologies may be used when pregnancy is desired. Because subjects with FHA are hypoestrogenic, the use of low-dose estrogens has been proposed as a putative treatment to positively modulate the spontaneous restart of gonadotropin secretion, counteracting the blockade of the reproductive axis triggered by stress acting through the neuroendocrine pathways at the basis of positive feedback of estrogens. The mechanism through which low-dose estrogens acts is still unknown, but kisspeptin-secreting neurons may be involved.

Casein and pea enriched high-protein diet attenuates arsenic provoked apoptosis in testicles of adult rats.

Arsenic toxicity is a major health issue that also threats male reproductive system leading to impairment of fertility. The antioxidant capacity of casein and pea enriched formulated high-protein diet (FHPD) is found to be effective in different toxicity management. The present study was endeavored to investigate the mitigatory aspect of FHPD on arsenic stimulated testicular apoptosis. Adult male rats were maintained on either normal diet as control (Gr I, n=8) and arsenic (As2O3) treated at a dose of 3mg/kg/rat/day (Gr II, n=8) or on isocaloric FHPD as supplemented (Gr III, n=8) with same dose of arsenic for 30 consecutive days. Testicular histomorphometry, spermatokinetics, testicular functional marker enzymes, serum gonadotrophins, oxidative stress markers, testicular deoxyribonucleic acid (DNA) damage, and apoptosis markers were evaluated to assess the reprotoxicity of arsenic and subsequent protection by FHPD. FHPD protected the histopathological alterations and also restored normal spermatogenesis. Altered enzymatic activities of testicular functional markers like lactate dehydrogenase, γ-glutamyl transferase, acid phosphatase, and alkaline phosphatase were also regularized. FHPD also reinstated the normal level of follicle stimulating hormone (FSH), luteinising hormone (LH), and also normalized the enzymatic activities of testicular glutathione peroxidase and glutathione reductase. Testicular DNA damage was also prevented by FHPD supplementation. Testicular apoptosis marked by the altered messenger ribonucleic acid and protein expression of apoptotic markers like Bax, Bcl-2, caspase 9, and caspase 3 were also attenuated upon FHPD supplementation along with diminution of arsenic accumulation in testicular tissues. FHPD not only mitigated the adverse effects of arsenic induced gonadotoxicity but also helped in sustaining the normal reproductive functions.

Nesfatin-1 regulates steroidogenesis in mouse Leydig cells

Nesfatin-1 is a polypeptide hormone known to regulate appetite and energy metabolism and is derived from the precursor protein nucleobindin 2 (NUCB2). Recent studies have shown that nesfatin-1 is expressed in many peripheral tissues in mice, including the reproductive organs. However, its function and regulation in the testis remain unknown. In this study, we investigated the expression of Nucb2 mRNA and nesfatin-1 protein in mouse Leydig cells and the Leydig cell line, TM3 cells. We also examined whether Nucb2 mRNA expression is regulated by gonadotropins and whether exogenous nesfatin-1 affects steroidogenesis in primary Leydig cells isolated from the testis and TM3 cells. We found that Nucb2 mRNA and nesfatin-1 protein were present in primary Leydig cells and TM3 cells, and nesfatin-1 binding sites were also found in both cell types. Nucb2 mRNA expression in testis, primary Leydig cells, and TM3 cells was increased after treatment with pregnant mare’s serum gonadotropin and human chorionic gonadotropin. After nesfatin-1 treatment, the expression of steroidogenesis-related enzyme genes Cyp17a1 and Hsd3b was upregulated in primary Leydig cells and TM3 cells. Our results suggest that NUCB2/nesfatin-1 expression in mouse Leydig cells may be regulated through the hypothalamic-pituitary-gonadal axis and that nesfatin-1 produced by Leydig cells may locally regulate steroidogenesis in an autocrine manner. This study provides insight into the regulation of NUCB2/nesfatin-1 expression in Leydig cells and the effect of nesfatin-1 on steroidogenesis, which may have implications for male reproductive health.

Production of Mare Chorionic Girdle Organoids That Secrete Equine Chorionic Gonadotropin.

The equine chorionic girdle is comprised of specialized invasive trophoblast cells that begin formation approximately 25 days after ovulation (day 0) and invade the endometrium to become endometrial cups. These specialized trophoblast cells transition from uninucleate to differentiated binucleate trophoblast cells that secrete the glycoprotein hormone equine chorionic gonadotropin (eCG; formerly known as pregnant mare serum gonadotropin or PMSG). This eCG has LH-like activity in the horse but variable LH- and FSH-like activity in other species and has been utilized for these properties both in vivo and in vitro. To produce eCG commercially, large volumes of whole blood must be collected from pregnant mares, which negatively impacts equine welfare due to repeated blood collections and the birth of an unwanted foal. Attempts to produce eCG in vitro using long-term culture of chorionic girdle explants have not been successful beyond 180 days, with peak eCG production at 30 days of culture. Organoids are three-dimensional cell clusters that self-organize and can remain genetically and phenotypically stable throughout long-term culture (i.e., months). Human trophoblast organoids have been reported to successfully produce human chorionic gonadotropin (hCG) and proliferate long-term (>1 year). The objective of this study was to evaluate whether organoids derived from equine chorionic girdle maintain physiological functionality. Here we show generation of chorionic girdle organoids for the first time and demonstrate in vitro production of eCG for up to 6 weeks in culture. Therefore, equine chorionic girdle organoids provide a physiologically representative 3D in vitro model for chorionic girdle development of early equine pregnancy.

NUCB2/nesfatin-1 suppresses the acrosome reaction in sperm within the mouse epididymis

ABSTRACT Nesfatin-1, a polypeptide hormone derived from the nucleobindin 2 (NUCB2) precursor protein, is known to regulate appetite and energy metabolism. Recent studies have also shown that NUCB2/nesfatin-1 is expressed in the reproductive organs of mice. However, the expression and potential role of NUCB2/nesfatin-1 in the mouse epididymis remain unclear. Therefore, we investigated the expression of NUCB2/nesfatin-1 in the mouse epididymis and its potential function. NUCB2/nesfatin-1 was detected in the epididymis by qRT-PCR and western blotting, and high expression levels were observed in epididymal epithelial cells by immunohistochemical staining. Pregnant mare’s serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) injections significantly increased NUCB2/nesfatin-1 expression in the epididymis. After castration, NUCB2/nesfatin-1 expression in the epididymis decreased, but was significantly increased by testosterone injection. Nesfatin-1-binding sites were found in the middle piece of testicular sperm, but were scarcely detected in the sperm head. By contrast, nesfatin-1 binding sites were identified on the sperm head within the epididymis. Furthermore, nesfatin-1 treatment inhibited the acrosome reaction in epididymal sperm. These results suggest that the nesfatin-1 protein produced in the epididymis binds to nesfatin-1 binding sites on the sperm head and plays a role in suppressing the acrosome reaction before ejaculation.

Immunohistochemistry of Leukemia Inhibitory Factor and Integrin αVβ3 in Mouse Endometrium Following Kisspeptin-54 Ovulation Trigger.

Kisspeptin (KP) is a group of hypothalamic neuropeptides encoded by KISS-1 gene. KP-54, a 54-amino-acid peptide, helps regulate the hypothalamic-pituitary-ovarian axis and plays a potential role in implantation. C57BL/6J female mice were superovulated via intraperitoneal injection of 5 International Units (IU) pregnant mare serum gonadotrophin (day 1). Forty-eight hours later, mice (5/group) were injected with phosphate-buffered saline (PBS) (group A), 5IU human chorionic gonadotrophin (hCG) (group B), or 3nmol KP-54 (group C). On day 7, mice were euthanized and uteri excised to create paraformaldehyde-fixed paraffin-embedded sections that were immunostained for the implantation markers: leukemia inhibitory factor (LIF) and integrin αVβ3 (ITG αVβ3). Slides were scored for intensity of staining in endometrial glandular epithelium (GE) and stromal cells (SCs) via histoscore (H-score). Data were analyzed using the Kruskal-Wallis test followed by the Mann-Whitney U test for pairwise comparisons. LIF expression was significantly higher in GE and SCs of mice triggered with KP-54 compared to placebo (P = .009 for both), but only higher than hCG trigger group in SCs (P = .009). Meanwhile, ITG αVβ3 expression was significantly higher in SCs of mice triggered with KP-54 compared to placebo (P = .028). In conclusion, using KP-54 as an ovulation trigger resulted in higher expression of the implantation markers LIF and ITG αVβ3 in mice endometrium compared to hCG or placebo. This suggests a potential role for KP-54 trigger in improving embryo implantation in clinical IVF. However, further studies are needed to correlate these results with clinical implantation rates and pregnancy outcomes.

A Testicular Leydig Cell Tumor; An Uncommon Cause of Precocious Puberty: A Case Report With Secondary Central Precocious Puberty

Sexual precocity in boys is defined as any sign of secondary sexual characteristics present before the age of 9. Leydig cell tumors of the testes are a rare cause of peripheral precocious puberty in boys. Here, we report 8 years and 4-month-old boys with signs of peripheral precocious puberty because of a testicular Leydig cell tumor that developed true precocious puberty after surgical removal. Examination of genitalia showed Tanner 4 hair growth. The penis length was 14.5 cm with a 2.5 cm width. The right testis was enlarged but the left testis was measured at 2cm in length and 1 cm in width. Laboratory results showed low serum gonadotropin levels and increased androgen levels. Testicular sonography reported one solid mass measured 31×28×15 millimeters. With a presumptive diagnosis of Leydig cell tumor, the patient underwent radical orchiectomy. Pathologic evaluation confirmed it. Two months after surgery, the diagnosis of central precocious puberty was confirmed according to physical examination and rising of serum gonadotropins. We started treatment with a Gonadotropin-releasing hormone (GnRH) agonist. Leydig cell tumor in children is an uncommon cause of precocious puberty. In every boy with the sign of peripheral precocious puberty and asymmetrical testicular enlargement, the testicular tumor should be considered. It may induce central precocious puberty after surgical resection and this diagnosis should be considered in the patient’s follow-up in the next visits.

Quercetin protects against levetiracetam induced gonadotoxicity in rats

The purpose of this study was to determine whether quercetin may counteract the negative effects of levetiracetam on rat reproductive capabilities by examining its influence on a few reproductive parameters following levetiracetam administration. Twenty (20) experimental rats were employed, with five (n = 5) animals per treatment group. Rats in group 1 received saline (10 mL/kg, p.o.) which served as control. Quercetin (20 mg/kg, p.o./day) was given to groups 2 and 4 for 28 days starting from 29 to 56 days, respectively. However, animals in groups 3–4 received LEV (300 mg/kg) once daily for 56 days with a 30-minute break in between treatments. All rats had their serum sex hormone levels, sperm characteristics, testicular antioxidant capability, and levels of oxido-inflammatory/apoptotic mediators evaluated. Additionally, the expression of proteins associated to BTB, autophagy, stress response was examined in rat testes. LEV increased sperm morphological defects and decreased sperm motility, sperm viability, sperm count body weight and testes weight, MDA and 8OHdG levels in the testis of LEV-treated rats were elevated, while antioxidant enzyme expression was concurrently decreased. Additionally, it reduced the levels of serum gonadotropins, testosterone, mitochondrial membrane potential, and cytochrome C liberation into the cytosol from the mitochondria. Caspase-3 and Caspase-9 activity increased. While Bcl-2, Cx-43, Nrf2, HO-1, mTOR, and Atg-7 levels were lowered, NOX-1, TNF-α, NF-kß, IL-1ß, and tDFI levels increased. Histopathological scoring provided further support for the decreased spermatogenesis. In contrast to all of these gonadotoxic effects of LEV, improvements in LEV-induced gonadal damage were seen through upregulation of Nrf2/ HO-1, Cx-43/NOX-1, mTOR/Atg-7 expression and attenuation of hypogonadism, poor sperm quality, mitochondria-mediated apoptosis, and oxidative inflammation due to quercetin post-treatment. The modulation of Nrf2/HO-1, /mTOR/Atg-7 and Cx-43/NOX-1 levels and the inhibition of mitochondria-mediated apoptosis and oxido-inflammation in LEV-induced gonadotoxicity in rats suggest that quercetin may hold promise as a possible therapeutic treatment.

Bioactivity and Pharmacodynamics of X002, A Follicle-Stimulating Hormone-IgG4 Fc Fusion Protein.

Current follicle-stimulating hormone (FSH) drugs meet safety criteria but have suboptimal efficacy, poor patient compliance, and high cost. Alternative FSH-like drugs would help to meet the high market demand. Here, we evaluated X002, an FSH-Fc fusion protein, for bioactivity and half-life in vitro and in vivo. In all cases, the effects of X002 were compared with those of a commercially available short-acting FSH recombinant hormone. First, female Kunming mice (age, 21 to 24 d) were stimulated with pregnant mare serum gonadotropin (PMSG) for 46 h, after which naked oocytes were harvested, treated with X002 or the comparison agent at 37 °C for 4 h, and then evaluated for germinal vesicle breakdown. Second, cumulus-oocyte complexes (COC) were collected from PMSG-stimulated mice and cocultured with X002 or the comparison agent for 14 h; the COC diameters were then measured, and the expression of genes involved in COC expansion were evaluated using quantitative RT-PCR analysis. Third, to assess the pharmacokinetics of X002, female Sprague-Dawley rats (age, 6 to 8 wk) were injected subcutaneously with X002 or the comparison agent; serum samples then were collected at various times and assessed via ELISA. Fourth, to evaluate X002 pharmacodynamics, 26-d-old female Sprague-Dawley rats were treated with X002 or the comparison agent; 84 h later, the rats were stimulated with human chorionic gonadotropin (hCG). At 12 h after hCG injection, euthanasia was performed. Ovaries were removed and weighed, and serum levels of estradiol and progesterone were measured. Finally, to assess superovulation, the oocytes in the fallopian tubes were counted at 108 h after in vivo treatment of rats with X002 or the comparison agent. The data show that X002, a long-acting agent, promoted germinal vesicle breakdown and COC expansion in vitro and in vivo ovarian weight gain and superovulation to a degree similar to the short-acting comparison agent.

Ceruloplasmin and complement C3 are markers of diminished ovarian reserve in premenopausal women

Aim. To establish cut-off values for the concentrations of complement C3 and ceruloplasmin, diagnostic markers of reduced antral follicle count (AFC) and anti-Müllerian hormone (AMH) which both indicate diminished ovarian reserve, in women of reproductive age.Materials and Methods. Here we enrolled 864 women (18-40 years of age, average age 31.70 ± 5.14 years) who underwent an annual medical examination in 2017–2019 in the Irkutsk Region and the Republic of Buryatia. Reduced AFC was defined as ≤ 5 antral follicles in each ovary at pelvic ultrasound examination whilst reduced AMH was defined as < 1.2 ng/mL. In total, 112 women had reduced ovarian reserve and 752 were included into the control group. In addition to AMH, we also measured serum prolactin, gonadotropins, inhibin B, estradiol, complement C3, and ceruloplasmin using enzyme-linked immunosorbent assay. The cut-off values were determined by plotting a receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC).Results. The cut-off level of complement C3 was 894 (867; 1355.5) mg/mL [AUC: 0.769 (0.635; 0.904)] in women with reduced AFC (≤ 5) and 981.5 (916.5; 1467.5) mg/mL [AUC: 0.62 (0.493; 0.746)] in women with reduced AMH (< 1.2 ng/mL). The cut-off level of ceruloplasmin was 1.745 (1.625; 1.975) mg/mL [AUC: 0.859 (0.759; 0.96)] in women with reduced AFC (≤ 5) and 1.975 (1.665; 2.15) mg/mL, [AUC: 0.662 (0.542; 0.782)] in women with reduced AMH (< 1.2 ng/mL).Conclusion. We have established the cut-off values for the serum complement C3 and ceruloplasmin in women with reduced AFC and AMH, indicators defining diminished ovarian reserve in women of reproductive age.

Nigella sativa-Floral Honey and Multi-Floral Honey versus Nigella sativa Oil against Testicular Degeneration Rat Model: The Possible Protective Mechanisms

The male reproductive function, particularly the testes, and the related hormones are sensitive to various xenobiotics. This work aimed for the first time to assess Nigella sativa floral honey (NS floral honey) and multi-floral honey (M-floral honey) versus Nigella sativa oil (NS oil) against rat testicular degeneration induced with azathioprine (AZA). A total of 40 male Wister rats were assigned into 5 groups: (1) control, (2) 15 mg/kg of AZA, (3) AZA + 1.4 mL/kg of M-floral honey, (4) AZA + 1.4 mL/kg of NS floral honey, and (5) AZA + 500 mg/kg of NA oil. Total testosterone (TT), free testosterone (FT), free androgen index (FAI), gonadotrophins, sex-hormone-binding globulin (SHBG), apoptosis markers, and redox status were assessed to clarify the possible protective mechanisms. Pituitary-testicular axis disruption, apoptosis markers, poor redox status, and sperm quality (count, viability, and motility) were set with AZA. Serum TT, SHBG, and absolute and relative testis weight were significantly restored in the NS oil and NS floral honey groups. Meanwhile, the NS oil group exhibited a significant elevation in FT and FAI. Serum gonadotrophins increased significantly in the NS floral honey (p < 0.01) and M-floral honey and NS oil (p < 0.05) groups. Testicular caspase-3, caspase-9, and nitric oxide showed significant improvement in the NS floral honey and NS oil groups. NS oil supplementation significantly normalized redox status (p < 0.05), whereas NS floral honey improved malondialdehyde and superoxide dismutase activity. Sperm quality exhibited a significant improvement in the NS oil group (p < 0.05). M-floral honey did not show reliable results. Although NS floral honey could protect against testicular damage, it did not upgrade to the level of improvement achieved with NS oil. We claim that further clinical studies are essential for focusing on the quality and quantity of bioactive constituents.

Protective Role of Kelulut Honey against Toxicity Effects of Polystyrene Microplastics on Morphology, Hormones, and Sex Steroid Receptor Expression in the Uterus of Rats.

Microplastics (MPs) are an emerging global pollutant. Previous studies have revealed that chronic exposure to MPs can affect animal and human reproductive health, particularly by impairing the reproductive system's normal functions, which may increase the risk of infertility in both males and females. Kelulut honey (KH), an excellent source of antioxidants, has been used to counteract the disruptive effects of Polystyrene microplastics (PS-MPs) in the rat uterus. Thus, this study aimed to investigate the potential protective effects of Kelulut honey against PS-MPs-induced uterine toxicity in pubertal rats. Prepubertal female Sprague Dawley rats were divided into four groups (n = 8): (i) normal control group (NC: treated with deionized water), MPs-exposed group (M: exposed to PS-MPs at 2.5 mg/kg), (iii) Kelulut honey group (DM: pretreated with 1200 mg/kg of KH 30 minutes before they were administered with PS-MPs at 2.5 mg/kg), and (iv) Kelulut honey control group (DC: only treated with KH at 2.5 mg/kg). The rats were treated orally once daily for six consecutive weeks. Uterine abnormalities in PS-MPs-exposed rats were significantly improved after concurrent treatment with Kelulut honey. Morphology improvement was observed and luminal epithelial cells seemed thicker with more goblet cells, glandular cells had a more regular and circular shape, stromal cell increased in size, interstitial gaps between stromal cells expanded, and the myometrium layer was thicker. Kelulut honey treatment also effectively normalized the suppressive effect of PS-MPs on the expression and distribution of sex steroid receptors (ERα and ERβ), as well as the level of serum gonadotropin (LH and FSH) and sex steroid (estradiol and progesterone) hormones. Kelulut honey can protect the female reproductive system against the disruptive effects of PS-MPs. The phytochemical properties of Kelulut honey might be responsible for these beneficial benefits. However, future studies are warranted to identify the mechanisms involved.

Live birth in woman with premature ovarian insufficiency and 46, XY karyotype after chemotherapy and bone marrow transplant: a case report

BackgroundPremature ovarian insufficiency (POI) is a clinical syndrome defined by loss of ovarian function before the age of 40 years, characterized by elevated serum gonadotropin levels and decreased estrogen levels with menstrual disturbance. POI can be natural or iatrogenic such as after chemotherapy, radiotherapy and surgery.Case presentationIn this study, we describe a successful live birth in a 31-year-old woman with POI and 46, XY Karyotype after being treated with chemotherapy and bone marrow transplant (BMT) for acute non-lymphocytic leukemia when she was 17 years old. With amenorrhea or oligomenorrhea for 11 years, her serum level of FSH was up to 35.0 IU/L and 53.0 IU/L taken 4 weeks apart, which can be diagnosed as POI. After controlled ovarian stimulation treatment for three cycles with different protocols and frozen-thawed embryo transfer (FET), she finally got a successful pregnancy and had a live birth later.ConclusionsThis case report serves as a reminder that karyotype of peripheral blood may mislead the diagnosis as disorders of sex development (DSD). It also demonstrates that it is possible for a woman with chemotherapy and bone marrow transplant induced POI can have successful pregnancy and live birth with appropriate therapy. Furthermore, as age may plays a predominant role in fertility rather than residual ovarian reserve, active treatment may be concerned for women with POI at younger age.

Transplantation of Aceh cattle ovary into the uterus of pseudopregnant local rabbits: Effect of post-transplant stress on uterine histopathology and ovarian follicle dynamics.

The increase in the levels of the cortisol hormone caused by the stress conditions generated by an ovary transplantation procedure can damage the uterus of the transplant recipient as well as the transplanted ovaries. This study aimed to analyze the histopathological changes that occur in the uterine horn of pseudopregnant local rabbits (recipients), as well as the ovarian follicular integrity of the donor Aceh cattle after transplantation. After 30 days of adaptation, all rabbits were divided into three treatment groups: R1 (the group of rabbits that underwent ovarian transplantation for 3 days, n = 5), R2 (the group of rabbits that underwent ovarian transplantation for 5 days, n = 5), and R3 (the group of rabbits that underwent ovarian transplantation for 7 days, n = 5). Pseudopregnancy induction was performed using the pregnant mare's serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) methods. The rabbits were injected with 100 IU of PMSG intramuscularly, followed by an injection of 75 IU of hCG intravenously 3 days later. Ovarian transplantation was performed on day 8 (day 0 was the day of hCG injection). The concentration of cortisol hormone metabolites was measured from fecal samples using an enzyme-linked immunosorbent assay technique. The uterus and ovaries were collected for histopathological and follicular dynamics examination after the transplantation process was completed. The mean cortisol levels (ng/g) recorded before versus after the transplant in the R1, R2, and R3 groups were 146.23 ± 17.60 versus 338.84 ± 302.79, 128.97 ± 81.56 versus 174.79 ± 101.70, and 124.88 ± 43.61 versus 321.91 ± 221.63 (p < 0.05), respectively. The examination of the histopathological appearance of the uterus revealed edema in the uterine lumen, hyperemia and hemorrhage in the endometrium, necrosis of the epithelium, and infiltration of inflammatory cells. Hemorrhage and hyperemia were severe and filled the endometrium in the R1 compared with the R2 and R3 animals. Ovarian follicle development occurred in all treatment groups, although some histopathological features were observed. The number of tertiary follicles in R1, R2, and R3 animals was 24.67 ± 7.37, 20.67 ± 7.57, and 9.67 ± 3.79 (p < 0.05), respectively. Based on the results of this study, it can be concluded that the transplantation of ovaries from Aceh cattle into pseudopregnant local rabbits triggered an increase in the levels of the cortisol hormone and uterine histological changes; however, follicles were still detected at various stages of development in the transplanted Aceh cattle ovaries. The results of this study are valuable for clinicians and researchers because they provide information regarding an alternative in vivo ovarian preservation technique using pseudopregnant rabbits.

Effects of the body mass index of males on hormone levels, sperm and embryo parameters, and clinical outcomes in non-obstructive azoospermia: a systematic review and meta-analysis.

Research has shown that the body mass index (BMI) is not correlated with sperm retrieval outcomes, while serum testosterone and gonadotropins are related to the BMI in non-obstructive azoospermia (NOA). Previously, no comprehensive assessment had been conducted on the effect of the BMI of males in NOA. This study sought to comprehensively evaluate the effects of the BMI of males on hormone levels, sperm and embryo parameters, and clinical outcomes in NOA. The PubMed, Embase, Cochrane Library, and Web of Science databases were searched to retrieved relevant articles published up to May 27, 2022. Articles which examined patients with NOA (population), included patients with a BMI ≥25 kg/m2 (intervention) versus patients with a BMI <25 kg/m2 (comparator), assessed reproductive hormones, sperm and embryo parameters, and clinical outcomes (outcome), and were cohort studies (study design) were included. The quality of the included studies was assessed by the Newcastle-Ottawa Scale (NOS). A sensitivity analysis was conducted for all the outcomes. A total of 12 studies comprising 2,994 NOA patients were included. Patients with a BMI ≥25 kg/m2 had lower follicle-stimulating hormone (FSH) [pooled weighted mean difference (WMD): -0.67, 95% confidence interval (CI): -0.94 to -0.41, P<0.001] and total testosterone (TT) (pooled WMD: -1.35, 95% CI: -2.10 to -0.60, P<0.001) levels than those with a normal weight (BMI <25 kg/m2). The testicular volume of the BMI ≥25 kg/m2 group was larger than that of the normal weight group (pooled WMD: 0.26, 95% CI: 0.09 to 0.44, P=0.003). The average BMI of the group with successful sperm extraction was lower than that of the group with failed sperm extraction (pooled WMD: -0.97, 95% CI: -1.89 to -0.04, P=0.041). The live-birth rate of the BMI ≥25 kg/m2 group was lower than that of the normal weight group [pooled relative risk (RR) =0.88, 95% CI: 0.78 to 0.99, P=0.031]. The BMI of the males was an important factor affecting the FSH and TT levels, testicular volume, sperm retrieval success, and live-birth rate in NOA. Weight management may benefit NOA patients.

Effect of protection of enoxaparin against experimental ischemia/reperfusion injury in the rat ovary on in vitro fertilization outcomes.

The study aimed to investigate the protection of enoxaparin (E) against experimental ischemic (I) and ischemic-reperfusion (I/R) injury in rat ovaries on in vitro fertilization outcomes. In total, 56 adult female Sprague-Dawley albino rats were randomly assigned to 6 groups of 8 animals each: Sham, Ischemia, I/R, Sham+E, I+E, and I/R+E. Ischemia groups were subjected to bilateral adnexal torsion for 3 h. In contrast, I/R and I/R+E groups received subsequent detorsion for 3 h. Enoxaparin (0.5 mg/kg s.c.) was administered 30 min prior to ischemia (I+platelet-rich plasma) or reperfusion (I/R+I+platelet-rich plasma). Ovaries were stimulated through intraperitoneal injection of 150-300 internal units IU/kg pregnant mare serum gonadotropin. Anti-Müllerian hormone levels were measured before and after surgery in all groups. When the number of metaphase II oocytes was evaluated, statistically significant differences were observed between the I and I+E (p=0.001) and I/R and I/R+E (p=0.000) groups. When both I and I+E groups and I/R and I/R+E groups were compared, it was found that E application increased the number of fertilized oocytes. The number of embryos on the second day was higher in the I/R+E group than that in the I/R group. Statistically significant differences were found in the number of grade 1 embryos between the I/R and I/R+E groups (p=0.003). In comparing anti-Müllerian hormone values within the group, the highest decrease was observed in the I and I/R groups. Enoxaparin effectively minimizes ovarian damage and preserves ovarian reserve following ovarian torsion.

Quantitative Histomorphometry of Pre-ovulatory Follicles and Uterine Glands of Ongole-grade Heifer in Response to the Low Doses of PMSG Administration

Injection of female mammalian animals with gonadotropin prior to mating using superovulation dose increases estradiol 17beta (E2) synthesis and secretion and improves the growth and development of the uterus to support prenatal growth with the side effect of increasing litter size. This experiment was designed to study the effects of low doses of PMSG injection in heifers on the growth of granulose cells (GC) of pre-ovulatory follicles, E2 synthesis, and uterine glands growth and development. Nine Ongole-grade heifers were divided into three groups of doses of PMSG injection, i.e., 0 IU/kg BW, 0.5 IU/kg BW, and 1.0 IU/kg BW. The injection of pregnant mare serum gonadotropin (PMSG) was conducted at the early stage of the second follicle wave. Blood samples were collected at estrus (day 0) to measure plasma E2 concentrations. The ovary and uterus were collected for histological observation after slaughtering the animal. The results showed that non-superovulation doses of PMSG injections at the second follicle wave significantly increased the growth of GC that eventually produced a significantly higher plasma E2 concentration by 39.47% and 113.57%, in heifers receiving 0.5 IU/kg BW and 1.0 IU/kg BW (p<0.05), respectively. The increase in E2 synthesis and secretion significantly stimulated the growth and development of uterine glands (p<0.05), which was reflected in the improved measures of uterine glands. In conclusion, injections of heifers with low doses of PMSG at the second follicle wave could increase the growth of GC to produce a higher secretion of E2 that eventually improves the growth and development of uterine glands in the endometrium without the risk of multiple calving.

Clinical significance and pitfalls of human chorionic gonadotropin-related tumor markers for intracranial germinomas.

Measuring serum and cerebrospinal fluid human chorionic gonadotropin (hCG) is essential for the diagnosis of intracranial germ cell tumors. There are three types of hCG-related markers in clinical use: hCGβ, intact hCG, and total hCG. The best marker for the diagnosis of intracranial germ cell tumors, especially germinoma, is currently unknown. This study aimed to evaluate the usefulness of these hCG-related markers. We investigated 19 serum samples obtained from 6 patients with histologically diagnosed germinoma treated in our institute. Serum hCGβ, intact hCG, and total hCG values were measured before, during, and after treatment. Samples with hCG values above the lower limits were considered positive. The positivity rates of serum hCGβ, intact hCG, and total hCG were 6% (1/17), 47% (7/15), and 42% (8/19), respectively, with the latter two having significantly higher positivity rates than hCGβ (p = 0.041). Both intact and total hCGs showed similar values. The median values of hCGβ, intact hCG, and total hCG before treatment were 0.1ng/mL, 4.6mIU/mL, and 4.5mIU/mL, respectively. Serum intact and total hCGs have higher detection rates than hCGβ in patients with germinoma using available commercial measurement tools.

On sex hormones in infertiled men The effect of ghrelin

The present study was designed to evaluate the effect of ghrelin on sex hormones, follicle stimulating hormones, luteinizing hormones, Testosterone, and prolactin in infertiled men. Abnormal spermatogenesis is often associated with altered serum gonadotropins and testosterone. follicle stimulating hormones, luteinizing hormones, and testosterone levels They were estimated in 50 infertiled men. Results showed statistically significant increase (p&lt; 0.05) in the mean of ghrelin, follicle stimulating hormones, luteinizing hormones, Thyroid stimulating hormones, Prolactin, fasting blood sugar , Triglyceride, High density lipoprotein, Very low density lipoprotein, in all the studied infertiled males patients when compared with the fertiled control (n=20). In addition there was no significant differences in the levels of testosterone , Cholesterol ,and Low density Lipoprotein, between the infertiled and fertiled men.

The Levels of Pregnancy-Associated Plasma Protein (PAPP-A) and Chorionic Gonadotropin (β-hCG) in the Blood Serum of Women with Hypothyroidism in the 1st Trimester of Pregnancy.

Hypothyroidism occurs in pregnant women at a rate of 0.3% to 3%. The deficiency of thyroid hormones during pregnancy can lead to an increased risk of pregnancy complications and poor health of the child, particularly affecting its psychomotor development due to the intensive growth of the nervous system during gestation. The study attempted to establish the median concentrations of pregnancy-associated plasma protein PAPP-A and the free subunit of human chorionic gonadotropin β-hCG in women with hypothyroidism in the 1st trimester of pregnancy. The study attempted to establish the median concentrations of pregnancy-associated plasma protein PAPP-A and the free subunit of human chorionic gonadotropin β-hCG in women with hypothyroidism in the 1st trimester of pregnancy. The study included 210 pregnant women between 11 and 13.6 weeks of pregnancy; 105 women were diagnosed with hypothyroidism before or during pregnancy, and 105 women of a similar body weight and gestational age had normal thyroid function.The measurements of the pregnancy parameters studied were performed using the DELFIA® Xpress system. Differences in the multiples of the median of the PAPP-A and β-hCG levels between women with hypothyroidism and healthy women were observed. Introducing correction for patients with hypothyroidism during non-invasive biochemical prenatal testing may allow obtaining more reliable results that would be the basis for referral to invasive procedures.