Joint Genome-Wide Association Study Identifies Twenty-One Novel Loci for Age at Menarche and Highlights Its Causal Association with Other Complex Diseases

Age at menarche (AAM) is a sign of puberty of females. It is a heritable trait associated with various adult diseases. However, the genetic mechanism that determines AAM and links it to disease risk is poorly understood. Aiming to uncover the genetic basis for AAM, we conducted a joint association study in up to 438,089 participants from 3 genome-wide association studies of European and East Asian ancestries. Twenty-one novel genomic loci were identified at the genome-wide significance level. Besides, we observed significant genetic correlations between AAM and 67 complex traits, and the highest genetic correlation was observed between AAM and body mass index (rg=-0.19, P=6.11×10−31). Latent causal variable analyses demonstrate that there is a genetically causal effect of AAM on high blood pressure (GCP=0.47, P=0.02), forced vital capacity (GCP=0.63, P=0.02), age at first live birth (GCP=0.51, P=0.03), impedance of right arm (GCP=0.41, P<1×10-7) and right leg fat percentage (GCP=-0.10, P=0.02), etc. Enrichment analysis identified 5 enriched tissues and 51 enriched gene sets. Four of the five enriched tissues were related to the nervous system, including the hypothalamus middle, hypothalamo hypophyseal system, neurosecretory systems and hypothalamus. The fifth tissue was the retina in the sensory organ. The most significant gene set was the ‘decreased circulating luteinizing hormone level’ (P=2.45×10-6). Our findings may provide useful insights that elucidate the mechanisms determining AAM and the genetic interplay between AAM and some traits of women.

Leptin Receptor and Prolactin Are Prognostic Factors for Pubertal Disorders in Male Adolescents With Advanced Chronic Kidney Disease

Background: Few research studies have assessed chronic kidney disease (CKD) with pubertal disorders (PD) in adolescent boys and limited data are available. Thus, this study was planned to identify the usefulness of assessing hormonal parameters in male adolescents with CKD and their relationship with PD with a 1-y follow-up period.Methods: A prospective cohort study was performed on adolescents with CKD, stages IV and V. We collected information about the age at puberty onset, menarche, and the date of last menstrual period from the subjects’ clinical records and interrogation. A 1-y follow-up was conducted over pubertal development. At the beginning of the follow-up, the routine hormonal profile tests were performed to check the thyroid profile, prolactin level, luteinizing hormone level, follicle-stimulating hormone level, testosterone level, leptin level, and receptor leptin level. We compared the hormonal profiles of patients with and without PD (wPD vs. woPD). Comparisons between the groups were made using Wilcoxon and Fisher's tests. Logistic regression analysis was also performed.Results: Sixty-four patients, including 26 patients who were classified into the wPD group were analyzed. The median age of the study population was 15 y, and the median time for CKD evolution was 11 mon. There were no differences in the general and biochemical characteristics of wPD and woPD subjects. In terms of the hormonal measurements, the levels of prolactin were higher, while those of free leptin and free thyroxine were lower in wPD patients. Leptin receptor levels > 0.90 ng/mL (RR 8.6 p = 0.004) and hyperprolactinemia (RR 21.3 p = 0.049) were risk factors for the development of PD.Conclusions: Leptin receptor levels < 0.90 ng/mL and hyperprolactinemia are associated with the development of PD in male adolescents with CKD.

Effects of aqueous seed extract of Moringa oleifera (L) on haematology, gonadotropins and testosterone profiles of Yankasa rams

Introduction: Moringa oleifera is a multipurpose plant, which belongs to the family Moringaceae, and is recognised globally. Moringa oleifera aqueous seed extract was used to determine its effects on the haematology and some reproductive hormone profiles in Yankasa rams. Methods: Twenty-Five Yankasa rams weighing 18-20 kg, were purchased and kept at the experimental pen of the Department of Veterinary Parasitology and Entomology, Ahmadu Bello University, Zaria for this study. The rams were screened and acclimatized for 2 weeks prior to the commencement of the research. Thereafter, the rams were randomly divided into five groups A, B, C, D and E with five rams each as treatment and control groups respectively. The rams were fed basal diet of Digitaria smuttssi. Water was provided ad libitum. Group A, B, C, D and E were given oral dose of M. oleifera aqueous seed extract and water daily at a dose rate of 1000, 2000, 3000, 4000 mg/kg and 10 ml/kg respectively. Blood samples were collected via jugular vein once every week to evaluate packed cell volume (PVC %), total red blood cells (TRBC× 1012/L) and Total white blood cells (TWBC × 1012/L). To obtain sera blood was collected 3 times at 30 minutes interval between 7:00 and 8:00 A.M, the sera were evaluated for follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone concentrations in Yankasa rams. Results: Haematology results revealed significant (p < 0.05) increase in PCV in group C (37.5 ± 0.7 %). There was significant (p < 0.05) increase in the testosterone and luteinizing hormone level at 7:00 A.M in group A (5.42 ± 0.1 ng/ml). Also, there was significant (p < 0.05) increase in the levels of FSH, LH and testosterone. Significance: In conclusion, treatment of Yankasa rams with M. oleifera aqueous seed extract at the dose rate of 1000-3000 mg/kg increased testosterone, PCV, LH and FSH profiles. Therefore, M. oleifera aqueous seed extract may be recommended as a fertility enhancing agent in Yankasa rams.

Fucoxanthin-Rich Brown Algae Extract Improves Male Reproductive Function on Streptozotocin-Nicotinamide-Induced Diabetic Rat Model

Hypogonadism and oxidative stress are occurring commonly in men with diabetes and associated male infertility. This study aimed to investigate the capability of anti-oxidative and anti-inflammatory properties of fucoxanthin as well as to evaluate its protective effects on male reproduction in diabetic rats. The RAW 264.7 macrophage cells were used to evaluate the anti-oxidative and anti-inflammatory activity. Thirty male Sprague-Dawley rats were induced by streptozotocin-nicotinamide for a diabetes model and fed either with three different doses of fucoxanthin (13, 26, and 65 mg/kg) or rosiglitazone (0.571 mg/kg) for four weeks. The fucoxanthin significantly inhibited nitric oxide production and reduced reactive oxygen species level in lipopolysaccharide-induced RAW 264.7 cells. In the animal study, fucoxanthin administration improved insulin resistance, restored sperm motility, decreased abnormal sperm number, and inhibited lipid peroxidation. Moreover, it restored GPR54 and SOCS-3 mRNA expression in the hypothalamus and recovered luteinizing hormone level, as well as the testosterone level. In conclusion, fucoxanthin not only possessed antioxidant and anti-inflammatory properties but also decreased the diabetes signs and symptoms as well as improved spermatogenesis and male reproductive function.

The Pulsatile Gonadorelin Pump Induces Earlier Spermatogenesis Than Cyclical Gonadotropin Therapy in Congenital Hypogonadotropic Hypogonadism Men

The objective of this study was to compare the effect of pulsatile gonadorelin pump (PGP) and cyclical gonadotropin (human chorionic gonadotropin [HCG]/human menopausal gonadotropin [HMG]) therapy (CGT) on spermatogenesis in congenital hypogonadotropic hypogonadism (CHH) men. Twenty-eight azoospermic CHH males were included in this nonrandomized study. Ten received PGP and 18 received CGT. The primary endpoint was the earliest time spermatogenesis occurred during 24 months of treatment. Spermatogenesis time was significant earlier in the PGP group than the CGT group (median of 6 and 14 months, respectively, χ2 = 6.711, p = .01). Spermatogenesis occurred in 90% of the PGP group and 83.3% of the CGT group and showed statistically insignificant difference in the superiority analysis and the no-inferior test. Contributing factors significant for spermatogenesis were previous HCG/or testosterone treatment and the peak serum luteinizing hormone level of triptorelin stimulation test at baseline. Although testis volume and penile length increased significantly from baseline, the differences between the two therapies were not significant. There was a tendency for high serum testosterone level, associated with more facial acne and breast tenderness in the CGT group. Skin allergic erythema scleroma was a common side effect of the PGP. In summary, PGP resulted in earlier spermatogenesis and more desirable testosterone levels than CGT.

Using micronized progesterone for treatment of premenopausal age women suffering from severe premenstrual syndrome

In this study, we carried out the clinical and laboratory research of severe PMS (premenstrual syndrome) treatment in premenopausal age women. Herein, 37 women were examined and observed before the beginning of treatment and three months after it. Medication containing micronized progesterone was used for treatment (sublingually, 100 mg from 11 to 25 days of menstrual cycle). After three months of micronized progesterone treatment, 86.5% of all women-participants of the study were observed to have full regression of clinical symptoms, while 13.5% of all patients were observed to have decrease in clinical symptoms of severe PMS. Moreover, hormonal research results revealed significant (1.3 times) decrease in LH (Luteinizing hormone) level and (1.3 times) increase in progesterone level after three months of treatment (р<0.05). The high bio-accessibility of the medication and its natural structure made it possible to decrease the dose and avoid risks of hepatotoxicity.