Serum FSH Concentrations Research Articles

Childhood reproductive hormone levels after pediatric hematopoietic stem cell transplantation in relation to adult testicular function.

ObjectivesLongitudinal assessment of testicular function after pediatric hematopoietic stem cell transplantation (HSCT) is needed to guide clinical follow-up. We investigated dynamics in male reproductive hormones after pediatric HSCT, focusing on pubertal timing and associations with testosterone deficiency and azoospermia in adulthood.MethodsThis retrospective, longitudinal study included 39 survivors median 19 years after pediatric HSCT. Serum concentrations of LH, testosterone, FSH, and inhibin B from the time of HSCT, during puberty, and into adulthood were analyzed. Pubertal timing (rise in LH and testosterone) was compared to a reference cohort of 112 healthy boys. Associations between reproductive hormone levels during puberty and adult testicular function (including semen quality) were investigated.ResultsPubertal induction with testosterone was needed in 6/26 patients who were prepubertal at HSCT. In the remaining patients, pubertal timing was comparable to the reference cohort. However, 9/33 patients (without pubertal induction) developed testosterone deficiency in early adulthood, which was associated with higher LH levels from age 14 to 16 years. Azoospermia in adulthood was found in 18/26 patients without testosterone substitution. Higher FSH and lower inhibin B levels from mid-pubertal age were associated with azoospermia in adulthood, in patients being prepubertal at HSCT.ConclusionOur results indicate a substantial risk of deterioration in testicular function after pediatric HSCT, despite normal pubertal timing. Although reproductive hormone levels from mid-puberty indicated adult testicular function, prolonged follow-up into adulthood is needed in these patients, including clinical examination, reproductive hormone analysis, and semen sample for patients interested in their fertility potential.

B-mode and Doppler Ultrasonography of Accessory Genital Glands and Testes in Male Goats During the Breeding Season

The aims of the present study were to scan the echogenicity of reproductive organs of bucks during the breeding season. The influence of testosterone on haemodynamic Doppler indices of accessory genital glands of breeding bucks was also examined. Ten clinically healthy, sexually mature, Egyptian Baladi male goats were examined and the testes, tail of epididymis and accessory sex glands imaged using greyscale B-mode, colour Doppler ultrasonography. The spectral Doppler indices (pulsatility index and resistive index) were measured. Blood samples were collected and serum concentrations of testosterone, FSH and LH were determined. The results revealed that the echogenicity of testes, tail of epididymis and accessory genital glands was changed by breeding season. Pulsatility index values of supra-testicular artery, marginal artery, tail of the epididymis, ampulla, vesicular gland, pars disseminata of the prostate and bulbourethral gland were 0.85±0.04, 0.54±0.03, 0.4±0.03, 0.37±0.04, 0.51±0.03, 0.39±0.02 and 0.41±0.04, respectively. The resistive index of the above criteria were 0.51±0.04, 0.37±0.02, 0.3±0.03, 0.27±0.02, 0.31±0.03, 0.32±0.03 and 0.32±0.03, respectively. Serum testosterone concentration was 4.78±0.46 ng/mL. Furthermore, FSH and LH were 3.71±0.43 and 1.8±0.17 mIU/mL, respectively. Interestingly, testosterone clearly deceased the values of the both the pulsatility and resistive indices of the accessory genital glands of breeding bucks. Season modified the echogenicity of testes, epididymis and accessory genital glands. Testosterone regulated the reproductive indices of blood flow of the accessory genital glands of breeding bucks. Thus, this study could serve as a baseline of reference values of Egyptian Baladi male goats during the breeding season to improve reproductive efficiency.

The Correlation between Pituitary Gonadotrophins, Gonadal Sex Steroid Hormone with Ferritin Level in Pubertal Females with Thalassemia Major at Wassit Province - Iraq 2020

Thalassemia Major still a growing disease in Iraq with no clear plan for prevention.
 Failure to get a secondary sexual character, amenorrhea, and then the inability to get pregnant is one the increasingly common problems in female patients with huge burden effects. Despite recent advances in iron chelation therapy, still, excess iron deposition in pituitary gonadotropic and gonadal cells remains one of the major causes for gonadal failure.
 Objectives: To evaluate the effect of iron overloads measured by serum ferritin on pituitary gonadotrophins measured by FSH, LH, and the gonadal sex steroid measured by estrogen in pubertal females with thalassemia Major.
 Methods: 41 female patients randomly selected in a cross-sectional study with diagnosed Thalassemia Major registered in Al-Kut Hereditary Blood Disease Center in the south of Iraq.
 Demographic data were evaluated including (age, type of chelation therapy, compliance for treatment and mean hemoglobin levels, and presence of amenorrhea). Serum ferritin, hemoglobin, FSH, LH, Estrogen levels were collected from patient's files. 
 Results: the age of the studied sample were range from 14-43 years. The majority of the studied patients 33(80.5%) were suffering from primary amenorrhea and only six had a normal menstrual cycle. Twenty-six (63.4%) patients had serum ferritin levels of more than 3000 ng/dl.
 A low average serum FSH, LH, and Estrogen concentration were observed in the group with serum ferritin levels more than 3000ng/dl in a statistically significant p-value, 0.001, 0.002, and 0.003 respectively with inverse Pearson's correlation (-0.4 and p-value 0.0009 for FSH), (- 0.2 with no significant p-value 0.12, for LH) and (-0.3 with significant p. value 0.02 for estrogen level). 
 Conclusions:
 In this study majority of females with thalassemia, Major suffer from disruption of pituitary gonadotropins and possible gonadal sex steroid. High ferritin still is a statistically significant risk factor for gonadal failure.
 The needs for more strict iron control, early screening, and proper treatment of gonadotropin and gonadal sex steroid deficiency around the age of 13 years are essential to be offered. More studies and a larger sample are needed to confirm and/or add other risk factors in pubertal thalassemic females.
 
 

P–116 A 9-year monocentric retrospective analysis of glutaraldehyde-fixed and semithin section of testicular biopsies and TESE in azoospermic patients

Abstract Study question What is the outcome of testicular sperm extraction (TESE) after microinjection of frozen–thawed sperm and the correlation with histological analysis in azoospermic patients? Summary answer In our cohort of 240 azoospermic patients, sperm could be retrieved in 167 patients (69.6%). What is known already Testicular biopsy is a crucial assessment in reproductive practice with diagnostic and prognostic importance for ICSI. Divers histological procedures are used throughout the centres. There is increasing need to accurately analyse histological biopsies in order to characterise different type of spermatogenic failure and allows data storage of value in clinical practice and research. Compared with Bouin’s and formalin, glutaraldehyde fixed and semithin section of testicular biopsies have the advantage of yielding not only good cellular morphology but also it allows the possibility of performing electron microscopy. Study design, size, duration This is a monocentric retrospective study of TESE practice in azoospermic patients in Strasbourg University Hospital from February 2011 to December 2019. Participants/materials, setting, methods A total of 240 azoospermic patients underwent TESE followed by sperm cryopreservation when sperm were present and data of histological analysis and clinical outcome of ICSI were analysed. The analysis include initial hormonal status, type of azoospermia, body max index, classification of histological findings, freezing rate and outcome of ICSI-IVF procedure. Main results and the role of chance The mean age of 240 patients was 34.5 years. Out of all patients, 42% were diagnosed with obstructive azoospermia (OA) and 58% patients with non-obstructive azoospermia (NOA). There was no correlation of sperm retrieval with the body mass index. Overall, sperm could be retrieved in 69.6% patients. Spermatozoa were always successfully recovered in patients with normal testicular histological findings, 41.7% patients (n 100). Histological analysis revealed a Sertoli cell-only (SCO) syndrome in 27.5% cases (n 66), hypospermatogenesis in 14.2% (n 34), germ cell arrest in 7.9 (n 19) and mixed pattern in 8.3% (n 20). In patients with serum FSH concentrations >12 IU/l, 46% of patients (n 42) sperm were present at TESE. In patients with no sperm retrieval, 31.5% had normal FSH levels. Out of all men with elevated FSH, 63% had SCO pattern, 4% germ cell arrest, 21% hypospermatogenesis and 12% mixt patterns. In the group of patients with no sperm retrieved at TESE, histological analysis showed SCO in 69.9% cases, germ cell arrest in 15% and hypospermatogenesis in 9.6% of cases. Out of 167 patients with TESE and sperm cryopreservation, 126 patients undergone ICSI-IVF procedure and 80 babies were born. Limitations, reasons for caution This study is a retrospective analysis in a single centre. The cohort was not compared with groups of patients with different histological and fixation techniques. Wider implications of the findings: Accurate histological diagnosis is a prerequisite for research and clinical data collection and open the possibilities to include patients with NOA in subsequent detailed genetic screen. Trial registration number NA

P–587 Highly purified human menopausal gonadotrophin (HP-hMG, Menopur) as a ready-to-use solution for injection in pre-filled pen is bioequivalent to HP-hMG powder for reconstitution

Abstract Study question Are serum FSH levels after single subcutaneous dosing of HP-hMG in a liquid formulation and a powder formulation bioequivalent? Summary answer The 90% CIs for the geometric mean ratios of serum FSH AUCt and Cmax were both within 0.8000–1.2500, thus the two formulations are bioequivalent. What is known already For several decades, HP-hMG (Menopur) has been used for the treatment of infertility; its efficacy and safety compared to other gonadotropins have been consistently demonstrated in several prospective, randomised controlled trials and meta-analyses (Deeks et al 2018; Bordewijk et al 2019). Menopur powder for reconstitution is available in multidose and single dose formulations. Up to 3 single dose vials (each containing 75 IU) may be dissolved into 1 mL solvent for administration. Recently, and for the first time, Menopur has been successfully formulated in a stable, ready-to-use solution for injection, which may be administered by a pre-filled pen. Study design, size, duration This was a randomised, two-way crossover, single dose, bioequivalence trial comparing Menopur liquid injected by pre-filled pen, with Menopur powder injected by conventional syringe and needle. The primary endpoints were AUCt and Cmax of baseline-adjusted FSH. Pituitary-suppressed, healthy women were randomised to receive one treatment sequence including a single subcutaneous injection of 450 IU Menopur liquid (600 IU/0.96 mL) and of 450 IU Menopur powder by two subcutaneous injections of 225 IU in 1 mL. Participants/materials, setting, methods Blood samples were collected pre- and post-dose, until 9 days after each injection. The PK parameters of FSH and hCG were assessed by noncompartmental methods with adjustment for endogenous pre-dose levels. Highly sensitive and specific electrochemiluminescence immunoassays were used for quantification and the LLOQ of the FSH and hCG assays were 1.47 mIU/mL and 0.5 mIU/mL, respectively, and the total validated CV was within 5% for both assays. Main results and the role of chance In total, 76 women were randomised and 56 completed the trial. The main reason for discontinuation was insufficient pituitary suppression prior to the second administration of HP-hMG. The mean FSH and hCG serum concentration-time profiles were comparable between the two HP-hMG formulations. The geometric mean ratios and 90% confidence intervals of FSH for HP-hMG liquid versus HP-hMG powder were 1.12 [1.0562; 1.1889] for AUCt and 1.17 [1.0946; 1.2490] for Cmax, showing that the two formulations were bioequivalent. Maximal serum FSH concentrations were reached at 18.19 h for HP-HMG liquid and 15.55 h for HP-hMG powder. In addition to FSH, the PK parameters for hCG were compared between the two HP-hMG formulations. The geometric mean ratios and 90% confidence intervals for HP-hMG liquid versus HP-hMG powder were 0.93 [0.86; 1.01] for AUCt and 0.94 [0.86; 1.02] for Cmax. There was no difference between the two groups in the incidence or severity of adverse events, and both preparations were well tolerated. Mild injection site reactions were less common after administration of HP-hMG liquid by a single injection compared to HP-hMG powder by two injections and were mostly related to pain and erythema after drug administration. Limitations, reasons for caution This bioequivalence study is based on the comparison of single dose administrations in healthy female volunteers of reproductive age. Wider implications of the findings: The new HP-hMG solution for injection in a pre-filled pen will deliver the efficacy and safety of Menopur in a convenient delivery device. Trial registration number NA

The role of makorin ring finger protein-3, kisspeptin, and neurokinin B in the physiology of minipuberty.

There is no data regarding the interrelationships of circulating Makorin Ring Finger Protein-3 (MKRN3), Kisspeptin (KISS1), and Neurokinin B (NKB) concentrations during minipuberty in humans. To determine temporal changes in circulating concentrations of MKRN3, KISS1, NKB, and gonadotropins and investigate interrelationships between them in healthy full-term (FT) and preterm (PT) infants during minipuberty period. A prospective study of 6-month follow-up performed. Eighty-seven healthy newborns, 48 FT (19 boys/29 girls), and 39PT (21 boys/18 girls) (gestational age 31-37weeks), were included. Blood samples were taken at 7days (D7), 2months (M2), and 6months (M6) of age. Serum MKRN3, KISS1, NKB, LH, FSH, total testosterone (TT), and estradiol (E2) concentrations were measured. Seventy infants completed the study. MKRN3, KISS1, and NKB concentrations were similar in FT girls and boys. PT boys and girls also had similar concentrations of MKRN3, KISS1, and NKB. FT babies had significantly higher NKB concentrations than PT babies at D7, M2, and M6. MKRN3 and KISS1 concentrations do not differ between FT and PT babies. A strong positive correlation was found between MKRN3 and KISS1 at each time point and in all groups. FSH, LH, TT/E2 concentrations decrease while those of MKRN3 and KISS1 have a trend to increase toward the end of minipuberty. No correlation was detected between gonadotropins and MKRN3, KISS1, NKB concentrations. Strong positive correlation demonstrated between KISS1 and MKRN3 suggests that interrelationship between molecules controlling minipuberty is not similar to those at puberty.

Effectiveness of basal LH in monitoring central precocious puberty treatment in girls.

Treatment of central precocious puberty (CPP) is based on administration of GnRH agonists in order to suppress hypothalamic-pituitary-gonadal axis and thus induce the stabilization or regression of pubertal development. Our aim was to determine whether the single basal serum LH and/or FSH concentration could be an effective tool to assess the efficacy of treatment to suppress activation of hypothalamic-pituitary axis. Serum LH and FSH were measured before and after the GnRH injection, as well as E2 basal levels in 60 girls with documented idiopathic CPP at diagnosis and 18 and 30 months after the beginning of therapy. At diagnosis, peaks of >5IU/L of LH and of FSH were observed in 100 and 91.6% of girls, respectively, with basal LH values of <1IU/L in 70% and basal FSH levels of <1IU/L in 10%. E2 were <20pg/mL in 36.6%. After 18 months, a suppressed peak (i.e. <3IU/L) was recorded in 85% of girls (p<0.01) for LH and in 98.3% for FSH (p<0.01). Basal LH <1IU/L was detected in 85% (p<0.01) and basal FSH ≤1IU/L in 40% (p<0.01). Serum E2 ≤20pg/mL was recorded in 61.6% (p<0.01). After 30 months, all patients showed LH suppressed peak (p<0.01) and 98.3% suppressed FSH peak (p<0.01). 100% showed basal LH concentrations <1IU/L (p<0.01) and 38.3% FSH basal values <1UI/mL (p<0.01). E2 ≤20pg/mL was observed in 32.72% (p=NS). Basal LH values are a reliable indicator of the efficacy of GnRHa therapy after 30 months of GnRHa therapy.

Doppler and B-mode ultrasonographic monitoring of accessory sex glands and testes in Barki rams during the breeding season

The aim of this study was to perform ultrasonographic imaging of the testes and accessory sex glands in adult Barki rams during the breeding season. The impact of testosterone on the Doppler indices of accessory sex glands was also investigated. Scrotal contents, pelvic urethra and accessory sex glands of twelve mature Barki rams were scanned with multiple imaging of B-mode and colour Doppler ultrasonography. Serum concentrations of testosterone, FSH and LH were determined. The results revealed that the breeding season changed the echogenicity of testicular parenchyma, spermatic cord, epididymal tail, glans penis and echotexture of accessory sex glands. Serum testosterone was 7.27±0.37 ng/mL, FSH was 6.46±0.2 and LH was 5.6±0.28 m IU/mL. The pulsatility index (PI) for the supra-testicular artery (STA), marginal artery (MA) of the testes and epididymal tail was 1.01±0.07, 0.58±0.04 and 0.5±0.04. The resistive index (RI) for the same structures was 0.6±0.04, 0.33±0.04 and 0.3±0.03, respectively. Importantly, testosterone downregulated PI and RI of the ampulla, vesicular gland, prostate gland and bulbourethral gland. In conclusion, the breeding season changed the echogenicity of reproductive organs and accessory genital glands of rams, and testosterone regulated the hemodynamic parameters of the accessory sex glands.

The impact of polycystic ovary syndrome and body mass index on the absorption of recombinant human follicle stimulating hormone.

Women with polycystic ovary syndrome (PCOS) have an increased ovarian responsiveness to exogenous recombinant follicle stimulating hormone (rFSH) but also have high rates of obesity, which is known to affect serum FSH concentrations following exogenous injection. The purpose of this study was to compare rFSH absorption and ovarian response between lean and overweight/obese PCOS subjects and normo-ovulatory controls. Fourteen women with PCOS aged 18-42years old with a BMI of 18.5-24.9kg/m2 (normal) or 25.0-40.0kg/m2 (overweight/obese) and eleven normo-ovulatory controls matched by age and BMI were included. After downregulation with oral contraceptives, participants were administered a single subcutaneous injection of 225IU rFSH and underwent serial blood draws over 72h. Lean PCOS subjects exhibited a significantly higher area under the curve (AUC) of baseline-corrected serum FSH over 72h when compared with overweight/obese PCOS subjects (183.3 vs 139.8IU*h/L, p= 0.0002), and lean, normo-ovulatory women had a significantly higher AUC FSH when compared with overweight/obese, normo-ovulatory women (193.3 vs 93.8IU*h/L, p< 0.0001). Within overweight/obese subjects, those with PCOS had a significantly higher AUC FSH compared with normo-ovulatory controls (p= 0.0002). Lean PCOS subjects similarly had the highest AUC of baseline-corrected estradiol (6095pgh/mL), compared with lean normo-ovulatory subjects (1931pgh/mL, p< 0.0001) and overweight/obese PCOS subjects (2337pgh/mL, p< 0.0001). Lean PCOS subjects exhibited significantly higher baseline-corrected FSH and estradiol levels following rFSH injection compared with overweight/obese PCOS subjects with similar ovarian reserve markers. Amongst overweight/obese subjects, those with PCOS had significantly higher FSH and E2 levels when compared with normo-ovulatory controls.

Distinguishing between hidden testes and anorchia: the role of endocrine evaluation in infancy and childhood

Non-palpable testes remain a diagnostic challenge, often involving exploratory laparoscopy. We evaluated the diagnostic value of a wide range of reproductive hormones in order to distinguish between bilateral cryptorchidism and bilateral anorchia. In this retrospective study, we identified and included 36 boys with non-palpable testes (20 with cryptorchidism, 3 with congenital hypogonadotropic hypogonadism (CHH), and 13 with anorchia) at first examination during childhood. Information on karyotype, phenotype, surgical results from laparoscopy, and biochemistry was retrieved from patient files. We compared serum concentrations of AMH, inhibin B, FSH, LH, testosterone, estradiol, and hCG stimulation testing in cryptorchid and anorchid boys to serum concentrations in a large, age-matched control group. Receiver-operating characteristic curves were used to determine the cut-off values of each reproductive hormone as a predictor of the presence of functional testicular tissue. Concentrations of AMH in 0-1 year olds: ≥155 pmol/L and >1-15 year olds: ≥19 pmol/L, inhibin B (≥22 pg/mL and ≥4 pg/mL), FSH (≤28.9 IU/L and ≤20.3 IU/L) and hCG-induced testosterone (>1-15 year olds: ≥2 nmol/L) were significantly sensitive and specific markers in predicting the presence of functional testicular tissue in boys with non-palpable testes. In infancy, anorchid infants had significantly elevated gonadotropin levels, while CHH had low levels. Our findings suggest that laparoscopy may not be necessary in all boys with non-palpable testes if reproductive hormones unequivocally confirm the presence of functional testicular tissue. However, proving the absence may still be a diagnostic challenge.

Menstrual Pattern, Reproductive Hormones, and Transabdominal 3D Ultrasound in 317 Adolescent Girls.

The knowledge of normal variation of reproductive hormones, internal genitalia imaging, and the prevalence of gynecological disorders in adolescent girls is limited. The study aimed to describe reproductive parameters in postmenarchal girls from the general population including the frequency of oligomenorrhea, polycystic ovary syndrome, and use of hormonal contraception. The Copenhagen Mother-Child Cohort is a population-based longitudinal birth cohort of 1210 girls born between 1997 and 2002. University hospital. A total of 317 girls were included, with a median age of 16.1 years and time since menarche of 2.9 years. Tanner stage, height, weight, age at menarche, menstrual cycle length and regularity, ovarian/uterine volume, and number of follicles were recorded. Serum concentrations of FSH, LH, anti-Müllerian hormone (AMH), inhibin B, estradiol, testosterone, SHBG, androstenedione, dehydroepiandrosterone sulfate, 17-OH-progesterone, and IGF-1 were measured. Twenty girls (6.3%) had oligomenorrhea and differed significantly in serum androgens and AMH, age at and time since menarche from girls with regular cycles. Twenty-seven girls were classified with PCOS (8.5%) and had significantly higher 17-OH-progesterone, estradiol, AMH, LH, and age at menarche than the reference group. Girls on oral contraception had significantly higher serum SHBG concentrations and lower serum concentrations of all hormones except AMH and IGF-1. Ovarian follicles 2 to 29.9 mm correlated positively with serum AMH (P < 0.0001). Most 16-year-old girls had regular menstrual cycles, normal reproductive hormones, and uterine and ovarian ultrasound. Serum AMH reflected ovarian follicle count and may be a useful biomarker of ovarian reserve.

Endocrinological Testicular Dysfunction in Patients with Lepromatous Leprosy and the Impact of Disease on Patient's Quality of Life.

Introduction:Leprosy or Hansen's disease poses a drastic impact on the quality of life in affected patients even after successful completion of treatment. The involvement of the endocrine system in leprosy is usually insidious, silent, and under-reported, especially the testicular dysfunction.Aims and Objectives:The present study was aimed at evaluating the abnormalities of the primary testicular hormone testosterone and the gonadotrophins LH and FSH in male patients affected with lepromatous leprosy and assessing the impact of the disease on quality of life (QOL).Materials and Methods:The study included 43 married male patients diagnosed with lepromatous leprosy. Careful history taking and examination for symptoms of testicular dysfunction were done. Serum concentrations of total testosterone, FSH, and LH were noted. The QOL was evaluated using the WHO Quality of Life-BREF (WHOQoL-BREF).Results:The most common clinical manifestation of testicular dysfunction was reduced or loss of libido reported in 12 (27.9%) patients followed by gynaecomastia in 7 (16.3%). Ultrasonographic (USG) analysis revealed reduced testicular volume in 31 (72.1%) patients, and average testicular volume was 11.9 ± 4.9 mL each. Seventeen (39.5%) patients had low serum testosterone levels, 9 (20.9%) had high serum FSH level, and 11 (25.6%) high LH levels. There was a significant negative correlation between testosterone level and FSH as well as LH. There was also a significantly positive correlation between testicular volume and testosterone level. Symptomatic patients with gynaecomastia/gynaecothelia had higher hormonal derangement than those who had other symptoms. On QOL, most patients scored lowest on the domain of “social relationships” (including sexual wellbeing) followed by “psychological health”.Conclusion:We found a high rate of USG diagnosed testicular atrophy in lepromatous leprosy patients. Therefore, every leprosy patient should be thoroughly examined clinically to rule out features of testicular dysfunction. Testicular function tests should be routinely carried out in all leprosy patients to arrive at an early diagnosis. Leprosy is found to affect all domains of a patient's quality of life.

CREM, PRM I and II gene expression in Wistar rats testes treated with antipsychotic drugs: Chlorpromazine, Rauwolfia vomitoria and co-administration of reserpine, zinc and ascorbic acid.

Objective:The literature has shown that synthetic antipsychotic drugs induce reproductive toxicity, while psychiatric patients treated with traditionally used antipsychotic herbs (Rauwolfia vomitoria) showed no traces of reproductive toxicity. Thus, this study aimed to investigate the expression of CREM, PRM I and II genes in the testes of Wistar rats treated with antipsychotic drugs: chlorpromazine, Rauwolfia vomitoria (RV) and co-administration of reserpine, zinc and ascorbate (RAZ).Methods:Forty-five adult male Wistar rats with rats with average weight of 180±4.67g were divided into nine groups (A-I) (n=5). Group A was administered saline (control) while rats in Groups B and C received 10 and 20mg/kg body weight (bwt) of chlorpromazine respectively. Groups D and E received 2.5 and 5mg/kg bwt of reserpine, respectively; while Groups F and G received 150 and 300mg/kg bwt of RV leaf extract. Groups H and I received (2.5+5+100) mg/kg bwt and (5+10+200) mg/kg of combination of RAZ, respectively for 56 days.Results:The CREM, PRM I and II genes were significantly downregulated while significant decreased in serum FSH and testosterone concentration were found in the Chlorpromazine- and Reserpine-treated groups. Groups H and I showed a highly significant upregulation of the CREM, PRM I and II genes, and a highly significant increase in serum FSH and testosterone concentrations.Conclusion:The study concluded that the HPT-Axis was impaired by chlorpromazine and reserpine, while RV and a combination of RAZ administration enhanced the axis in an animal model. The study recommended that synthetic antipsychotic drugs should be taken with Zinc and Ascorbate in order to help prevent reproductive toxicity associated with antipsychotic drugs. We need further studies in humans to confirm these findings.

Relationship between Body Mass Index (BMI) and testicular and hormonal parameters of sexually active male greater cane rats (Thryonomys swinderianus)

The current upsurge in intensive farming practices of greater cane rat has not only lead to higher growth rate but is accompanied by increased fat deposition especially in the males. This study attempts to characterize one of the most commonly used fat estimation parameter, the body mass index (BMI) as well as evaluates its relationship with testicular and hormonal parameters in seventy-two sexually active male cane rats over a period of one year. Six animals, kidded and raised in a farm, with known ages were used each month. The experimental protocols entail body measurements of weight, height and length; histology; orchidometry; and hormonal immunoassay of testosterone, estradiol, progesterone, LH and FSH using their various kits. The mean values of the body mass (BMI) and Lee (LI) indices of male greater cane rats were 1.18±0.20g/cm2 and 0.30±0.02g/cm respectively with the testicular histology indicating normal spermatogenesis. BMI/LI, both of which followed the same pattern, neither correlate with testicular parameters nor with serum testosterone, progesterone, LH and FSH concentrations but had low correlations with serum estradiol concentration (r2 = 0. 2; p = 0.0023). So, these relationships may provide clue on obesity and its effect on reproductive performance and strengthened the possibility of the characterized BMI/LI as obesity marker for breeding selection in male cane rat.

Use of clomiphene citrate protocol for controlled ovarian stimulation impairs endometrial maturity.

Introduction:Despite recent advances in assisted reproduction techniques and recent knowledge regarding embryo and endometrium quality, implantation and birth rates remain low. The objective of this study was to investigate whether clomiphene citrate alters endometrial maturation in infertile patients.Methods:In a prospective self-matched cohort study, we assessed the ovulation of women in spontaneous and stimulated cycles (with clomiphene citrate). We determined the ovulation day by ultrasound scanning. In both cycles, we took four blood samples (BS1 - at early proliferative phase, BS2 - at mid proliferative phase, BS3 - after ovulation and BS4 - at mid luteal phase) to determine the serum concentrations of FSH, LH, estradiol and progesterone. We retrieved an endometrial biopsy five days after ovulation, followed by blinded analysis and classification according to Noyes criteria, in both cycles.Results:Twenty-two participants completed the study. There were significant differences in FSH BS3 (p=0.001), in LH BS3 and BS4 (p<0.001 and p=0.049, respectively), in estradiol BS2, BS3 and BS4 (p<0.001, p=0.024 and p<0.001, respectively) and in progesterone BS3 and BS4 (p=0.028 and p<0.001, respectively). Considering Noyes criteria, there was a one-day delay when comparing the stimulated cycle with the spontaneous cycle (p=0.004), and a two-day delay when comparing the stimulated cycle with the biopsy day.Conclusion:This study indicates that ovarian stimulation with clomiphene citrate delays the endometrial maturity, and could possibly impair the implantation process due to asynchrony.

A case of premature ovarian insufficiency in Nijmegen breakage syndrome patient and review of literature. From gene mutation to clinical management

Background: Nijmegen breakage syndrome (NBS) is an autosomal recessive disorder leading to chromosomal instability and an array of symptoms, including characteristic facial features (bird-like face), predisposition to malignancies, as well as hypergonadotropic hypogonadism. This case report discusses the diagnostic process and management of a 23-year-old Polish female patient who was admitted to hospital with symptoms of secondary amenorrhea and clinical features corresponding to NBS.Methods: Clinical examination, per-rectal ultrasound, laboratory diagnostics (including serum concentrations of FSH, LH, estradiol, testosterone, and TSH), as well as SSCP analysis and classic karyotyping were performed.Results: During hormonal evaluation elevated serum concentration of FSH and LH and decreased serum concentration of estradiol were measured. The genetic testing revealed translocation 7;14 (t(7;14)) and inversion 7 in 22% of examined cells which confirmed the initial hypothesis of NBS. The diagnosis was finally verified by identifying a Slavic founder mutation, c.657_661del5, on both allels of the NBN gene. Furthermore, hormonal serum evaluation conducted after four weeks allowed the patient to be diagnosed with premature ovarian insufficiency (POI) suspected earlier on the grounds of preliminary examinations (ultrasound imaging and laboratory tests).Conclusions: Chromosomal instability resulting from a mutation present in Nijmegen breakage syndrome patients might be a causative factor of premature ovarian insufficiency. Therefore, females diagnosed with NBS should undergo additional diagnostic procedures in order to determine further management and treatment.

Role of epigenetic regulation of Igf2 and H19 in 2,3,7,8-Tetrachlorobenzo-p-dioxin (TCDD)-induced ovarian toxicity in offspring rats

2,3,7,8-Tetrachlorobenzo-p-dioxin (TCDD) exposure during embryonic gonadal sex determination had been demonstrated to harm the ovarian development. However, its mechanism was unclear and possibly related to epigenetic regulation. In the present study, the pregnant rats were treated with TCDD (100 ng/kg/day or 500 ng/kg/day) or only vehicle and corn oil on the day 8–14 of gestation through the gavage with a stainless-steel feeding needle. The vaginal opening time and estrous cycle of female offspring rats (F1) were monitored twice a day. The ovarian histology, follicle count, real-time PCR, Western Blotting and DNA methylation analysis for Igf2 and H19 were carried out. The results showed that maternal TCDD exposure disrupted estrous cyclicity, resulted in aberrant concentration of serum E2 and FSH, and affected the number of primordial follicles, secondary follicles and corpus luteum. However, TCDD had no effect on the number of primary follicles and atresia follicles. Furthermore, the mRAN expression of imprinted genes Igf2 and H19 was down-regulated, and the IGF2 protein was also down-regulated. TCDD exposure did not alter the mean methylation rate of Igf2 DMR2 and H19 ICR, and only some CpG sites throughout them were hypermethylated in high-dose TCDD rats. In conclusion, maternal exposure of TCDD could affect the ovary development and functions which were possibly associated with down-regulation expression of IGF2 and H19. However, it was not entirely clear whether the impairment of ovary by TCDD was related to the methylation pattern of Igf2 and H19 ICR.

Mancozeb impaired male fertility in rabbits with trials of glutathione detoxification

The study aims to evaluate the potential reproductive toxicity induced by mancozeb fungicide in male rabbits and to examine the ameliorative effect of glutathione (GSH), a non-enzymatic antioxidant, against mancozeb reproductive toxicity. Mancozeb is a member of the dithiocarbamates group currently in use in the management of fungal diseases of plants. To achieve these aims, mature male White New-Zealand rabbits of 4–5 months old were randomly assigned to four groups of 9 animals each: control, mancozeb only, mancozeb and GSH, and GSH only. This study discovered a significant reduction in serum FSH, LH, testosterone and testicular LDH, ACP, and ALP levels in the groups of mancozeb-treated rabbits compared with control. The mancozeb-treated groups also showed significant losses in sperm viability, along with a significant increase in the number of abnormal sperms. Finally, an upregulation in steroidogenic 3β-HSD enzyme activity was noted in mancozeb-treated rabbits. Histopathological inspection of the testicles established disruption of the germinal epithelium with vacuolization of Leydig cells and reduced spermatogenic cells. GSH co-administration increased serum concentrations of FSH, LH, testosterone, and levels of the testicular enzymes: LDH, ACP, and ALP. Improved steroidogenesis was indicated in this group by a significant improvement in the testicular 3β-HSD enzyme, by a significant increase in sperm viability, and by a significant decrease in the number of abnormal sperms. The findings of this study suggest that mancozeb exposure has anti-spermatogenic and anti-steroidogenic adverse effects in rabbits and administration of GSH may alleviate the reproductive toxicity.

CMTM2 is involved in spermiogenesis in mice

OBJECTIVE To investigate whether CKLF-like MARVEL transmembrane domain-containing protein 2 (CMTM2) is involved in spermatogenesis in mice. CMTM2 is highly expressed in testis, and could possibly be a potential spermagogenesis specific gene. METHODS CMTM2-deficient mouse model was generated. Northern, RT-PCR and Western blotting analysis were performed on total RNA derived from wild-type (WT, CMTM2+/+) and CMTM2+/- (heterozygote) and CMTM2-/-(homozygote) mice to examine the CMTM2 level. The number of litters and the number of pups were counted and pregnancy rates calculated. The motility and morphology of the sperm and the histology of testes were analyzed. Serum testosterone and FSH concentrations were also measured. Standard t-tests were used and standard error of means were calculated. RESULTS CMTM2 was highly expressed in a finely regulated pattern in the mouse testis during spermatogenesis. The body weight of adult mice with CMTM2 deficiency was not significantly different from that of wild type mice. No obvious anatomical or behavioral abnormalities were observed. The testis of CMTM2-/- was smaller than that of CMTM2+/+ mice. The testis diameter in wild mice and CMTM2 null mice were (11.32±1.21) mm vs. (8.29±1.92) mm (P<0.05), and the weights were (101.63±2.33) mg vs. (85.22±2.84) mg (P<0.05), respectively. Female CMTM2 null mice were fertile, indicating that CMTM2 was not required for female gametogenesis. The CMTM2-/- mice produced virtually no sperm, and CMTM2+/- mice sperm count showed a significant decline. In terms of sperm morphorlogy study, more round spermatids could be observed in the heterozygote group, compared with the wild type group; while in the homozygote group, a large amount of round spermatids could be observed because of complete arrest of spermiogenesis. The hormone levels were not significantly different. The CMTM2-/- male mice were sterile due to a late, complete arrest of spermiogenesis. The organized architecture of the seminiferous epithelium of the seminiferous tubules seen in CMTM2+/+ mice was lost in CMTM2-/- mice. CONCLUSION This study suggests CMTM2 is not required for embryonic development in the mouse but is essential for spermiogenesis, however, further studies are required for more detailed mechanism study.

Causes and consequences of the variation in the number of ovarian follicles in cattle

Summary. In cattle we have noted that the antral follicle count (AFC, follicles ≥3 mm in diameter) varies greatly among animals (from 5 to 50), is repeatable within animals, and is highly correlated with the total number of healthy follicles in ovaries. Also, animals with low AFC have higher serum concentrations of FSH and LH, but lower concentrations of Anti-Mullerian Hormone, progesterone and androgens than animals with high AFC. We have investigated the effect of maternal environment during gestation on their offspring AFC by restricting maternal nutrition to 60% of maintenance requirements (compared with 100% in controls) during the first third of gestation. Calves born to nutritionally restricted mothers had 60% lower AFC compared with calves born to mothers fed control diets. In other studies we have evidence to indicate that fertility may be compromised in animals with low AFC due to effects on oocytes, progesterone and the endometrium compared with animals with high AFC. To examine this directly we assessed AFC in post-partum dairy cows and found that cows with a high AFC had higher pregnancy rates, shorter calving to conception intervals and received fewer services during the breeding season compared with cows with a low AFC. In addition, the high variation in follicle numbers in adults may not only be reflective of reproductive disorders and suboptimal fertility, but there is evidence to indicate that it may be associated with alterations in the function of other non-reproductive systems (e.g. cardiovascular) that may have profound effects on the animal's health and welfare.