Effects of Bacillus subtilis ZJ-2019-1 on Zearalenone Toxicosis in Female Gilts

The purpose of this research was to investigate the toxicity of zearalenone (ZEN) on the growth performance, genital organs, serum hormones, biomarkers, and histopathological changes of female gilts and to evaluate the efficacy of Bacillus subtilis ZJ-2019-1 in alleviating ZEN toxicosis in gilts. Twenty-four female gilts were randomly allocated to four groups with six replicates per group and one gilt per replicate, fed on four feeds prepared previously, which were basic diet (control group, C group), ZEN diet (Z group), Zlb diet (Zlb group) containing B. subtilis ZJ-2019-1 in liquid form, and Zdb diet (Zdb group) containing B. subtilis ZJ-2019-1 in dehydrated form. The results showed that the vulva size and relative weight of reproductive organs had no significant difference in the control group, Zlb group, and Zdb group, but were significantly lower than in the Z group (p < 0.05); the relative weight of the liver was lower in the C group, Zlb group, and Zbd group than in the Z group (0.05 < p < 0.1). The concentration of serum glutamate dehydrogenase (GLDH) was lower, but follicle-stimulating hormone (FSH) was higher in the Z group, Zlb group, and Zdb group than in the Z group (0.05 < p < 0.1). Additionally, serum luteinizing hormone (LH) concentration had no significant difference in the C group, Zlb group, and Zdb group but was significantly lower than in the Z group (p < 0.05); estradiol (E2) was significantly lower in the Zlb group and Zdb group than that in C group, but significantly higher than that in Z group (p < 0.05); PRL was significantly higher in the Zlb group and Zdb group than in the C group, but was significantly lower than in Z group (p < 0.05). ZEN and its reduced metabolites were measured in biological samples after enzymatic hydrolysis of the conjugated forms. The concentration of serum ZEN and its metabolite, α-zeralenol (α-ZOL), had no significant difference in Zlb, Zdb, and control groups but was significantly lower than in the Z group (p < 0.05); urine ZEN and its metabolites, α-ZOL and β-zeralenol (β-ZOL), had no significant difference in Zlb, Zdb, and control groups but was significantly lower than in the Z group (p < 0.05). Cell damages were observed in the liver, uterus, and ovary of gilts in the Z group and alleviated in Zlb and Zdb groups, but the loss of oocytes was irreversible in the ovary. The ZEN-contaminated diet caused serious changes in female hormones and brought harm to the livers and reproductive organs, but B. subtilis ZJ-2019-1 could naturally remove the ZEN significantly, which ameliorated the reproductive impairment in gilts caused by ZEN. The addition of B. subtilis ZJ-2019-1 to ZEN-contaminated feeds could ameliorate the toxic effects effectively, regardless of liquid or dry culture. Therefore, the B. subtilis ZJ-2019-1 strain has great potential industrial applications.

Reproductive Regulation of PrRPs in Teleost: The Link Between Feeding and Reproduction

Prolactin-releasing peptide (PrRP), a sort of vital hypothalamic neuropeptide, has been found to exert an enormous function on the food intake of mammals. However, little is known about the functional role of PrRP in teleost. In the present study, two PrRP isoforms and four PrRP receptors were isolated from grass carp. Ligand-receptor selectivity displayed that PrRP1 preferentially binds with PrRP-R1a and PrRP-R1b, while PrRP-R2a and PrRP-R2b were special receptors for PrRP2. Tissue distribution indicated that both PrRPs and PrRP-Rs were highly expressed in the hypothalamus-pituitary-gonad axis and intestine, suggesting a latent function on food intake and reproduction. Using grass carp as a model, we found that food intake could significantly induce hypothalamus PrRP mRNA expression, which suggested that PrRP should be also an anorexigenic peptide in teleost. Interestingly, intraperitoneal (IP) injection of PrRPs could significantly induce serum luteinizing hormone (LH) secretion and pituitary LHβ and GtHα mRNA expression in grass carp. Moreover, using primary culture grass carp pituitary cells as a model, we further found that PrRPs could directly induce pituitary LH secretion and synthesis mediated by AC/PKA, PLC/IP3/PKC, and Ca2+/CaM/CaMK-II pathways. Finally, estrogen treatment of prepubertal fish elicited increases in PrRPs and PrPR receptors expression in primary cultured grass carp hypothalamus cells, which further confirmed that the PrRP/PrRPR system may participate in the neuroendocrine control of fish reproduction. These results, taken together, suggest that PrRPs might act as a coupling factor in feeding metabolism and reproductive activities in teleost.

Study the efficacy of cyproterone and metformin in modulation of hormonal disturbances in estrogen valerate induced PCOS in female rats

Polycystic ovarian syndrome (PCOS) is an endocrine disorder affecting women in child bearing age and is considered the main cause of infertility. This study aims to determine the efficacy of cyproterone 12 mg/ kg and metformin 50 mg/kg as a single oral daily dose for 20 days, in PCOS induced in female rats by estrogen valerate. In untreated group PCOS, the level of serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) was significantly (P< 0.0001) decrease, while estradiol and testosterone levels were increased significantly (P< 0.0001 and P< 0.001 respectively) in comparison with control group. Both cyproterone and metformin significantly increased LH and FSH levels (P< 0.05) compared to the untreated PCOS group. Both cyproterone and metformin reduced the level of estradiol hormone significantly (P <0.001 and P <0.05, respectively). Cyproterone also decreased the level of testosterone (P <0.0001) compared to the untreated PCOS group, and the testosterone level became less than that recorded in the control group (P <0.05), Metformin also significantly decreased the level of testosterone compared to the untreated PCOS group (P <0.01), but it still more than that in control. According to the results of the current study, we can conclude that cyproterone and metformin showed an efficacy in the treatment of PCO, and can restore the normal hormonal levels and should be considered in the treatment of this disease.

Macroautophagy Involved in Testosterone Synthesis in Leydig Cells of Male Dairy Goats (Capra Hircus)

Background Testosterone is an important steroid hormone that is indispensable for male sexual development and the reproductive system. Leydig cells (LCs), where autophagy extremely active, reside in the testicular interstitium and are the major sites of testosterone production. However, the ultrastructural characteristics and the functional role of autophagy in LCs of livestock remain unknown. This study was to investigate the role of autophagy in LCs testosterone synthesis of dairy goats at juvenile, pubertal, and adult stages. Results In the present study, morphological results showed that the steroidogenic activity and ultrastructure of the LCs were altered with increasing age. Serum luteinizing hormone and testosterone levels were significantly elevated with sexual maturation. Organelles involved in testosterone synthesis, e.g., smooth endoplasmic reticulum, mitochondria, and lipid droplets, were abundantly distributed within the cytoplasm of LCs in adult testes. However, further studies demonstrated that selective autophagy (including lipophagy and mitophagy) did not participate in the synthesis of testosterone in LCs. In contrast, the autophagy activity was enhanced in the testes at puberty and adulthood compared to that at the juvenile stage. Moreover, a number of different autophagosomes, including phagophores and autolysosomes, were observed within the cytoplasm of LCs. Conclusions Together, our results reveal that macroautophagy is involved in testosterone synthesis mainly through degrading mitochondria and endoplasmic reticulum in the LCs of dairy goats.

Hormonal effects of drosperinone and ethinyl estradiol based combined oral contraceptives on polycystic ovarian syndrome

Background: Polycystic ovarian syndrome (PCOS) is a common endocrine disorder treated with combined oral contraceptives (COCs). The androgenic potential of any type of COC is in part determined by the progestin present. A newer form of progestin, drospirenone, has been recently introduced, and is available in combination with ethinyl estradiol.Methods: The study was conducted on 60 patients fulfilling inclusion criteria, in the department of obstetrics and gynecology, Terna Medical College and Hospital. Patients were diagnosed as PCOS according to Rotterdam criteria. After initial evaluation, blood samples were sent for levels of serum luteinizing hormone (LH), follicle stimulating hormone (FSH), dehydroepiandrosterone-sulphate (DHEA-S), free testosterone, sex hormone binding globulin (SHBG). Each patient was advised to take a combination of EE (30 mcg) + drosperinone (3 mg), 1 tablet daily from the second day of her menstruation for 21 days then a 7 days gap and again for 21 days and so on cyclically for 3 cycles, then to repeat the tests as done at the beginning. Hirsutism was assessed clinically using the Ferriman-Gallwey scale at initial visit and three months later.Results: We found a significant improvement in the Serum LH, FSH levels and a significant fall in free testosterone levels accompanied by a rise in SHBG levels. There is also overall improvement in the hirsutism scores.Conclusions: Drosperinone based COCs are a good and effective means of treatment of PCOS. Treatment duration of three months was found to be effective in our study.

ASSOCIATION OF SERUM FOLLICLE STIMULATING HORMONE AND SERUM LUTEINIZING HORMONE WITH SECONDARY INFERTILITY IN OBESE FEMALES IN PAKISTAN

Objective: To finding the association of serum follicle stimulating hormone (FSH) and luteinizing hormone (LH) with secondary infertility in obese females in Pakistan. Study Design: Cross sectional study. Place and Duration of Study: District head quarter Hospital Sahiwal, from Mar 2018 to May 2018. Methodology: The study was conducted at district head quarter hospital Sahiwal after approval from Institutional Review Board of Sahiwal Medical College Sahiwal. The Data was assessed by IBM-SPSS version 24. Frequency distributions of study participants were calculated. Significance of the associations was assessed by independent sample t-test. Bivariate analysis was also done to check the effect of different factors on secondary infertility separately. The p-value less than 0.05 was taken as statistically significant. Results: Mostly (43.3%) belonged to middle class socioeconomic group. Nearly 54% were from urban residential areas. Majority belonged to (65%) age group between 31-40 years. When we calculated the association of serum follicle stimulating hormone and serum luteinizing hormone with the secondary infertility in these study participants then it was conclusive to find out that mean levels of both follicle stimulating hormone and luteinizing hormone were quite low (12.11 ± 1.14 and 21.97 ± 3.74 respectively) in patients with secondary infertility as compared to those which were not suffering from it. Association of serum follicle stimulating hormone was also found to be statistically significant with secondary infertility (p=0.042). Conclusion: Hence it is concluded that the low levels of serum follicle stimulating hormone are strongly associated with secondary infertility in obese women.

Dopamine receptor agonist rotigotine-loaded microspheres ameliorates sexual function deteriorated by fluoxetine in depression rats

Low dopamine levels may cause depressive symptoms. Dopamine is also involved in sexual behavior. Rotigotine is a nonergolinic dopamine agonist. Fluoxetine, an antidepressant that acts as a selective serotonin (5-HT) reuptake inhibitor, may cause moderate or severe sexual dysfunction. This study aims to investigate the effects of rotigotine-loaded microspheres (RoMS) and rotigotine on fluoxetine-induced impairment of sexual function and their efficacy in depression-model rats. Rats with depressive-like behavior, induced by bilateral olfactory bulbectomy, were treated intragastrically with fluoxetine and co-administered RoMS or rotigotine subcutaneously. Then, copulatory behavior and open field tests were conducted. Serum luteinizing hormone and testosterone levels were assayed with enzyme-linked immunosorbent assay kits. The concentrations of 5-HT, dopamine, and norepinephrine were measured in the raphe nucleus and amygdala. The results showed that sexual function was decreased in olfactory bulbectomy rats and significantly deteriorated by fluoxetine. Co-administration of RoMS partly reversed the fluoxetine-induced impairment of sexual function, but rotigotine administration did not produce any improvement. Hyperactivity in olfactory bulbectomy rats was significantly attenuated by fluoxetine but was not influenced by co-administration of RoMS. Compared with the fluoxetine group, RoMS increased the testosterone, luteinizing hormone, dopamine, and norepinephrine levels. These findings indicated that RoMS improved the fluoxetine-induced impairment of sexual function and did not affect its antidepressant efficacy in depressive rats, which provides a potential treatment for patients with depression that can reduce the possibility of sexual dysfunction. Additionally, co-administration of fluoxetine with RoMS may be beneficial for Parkinson's disease patients with depression.

Ablation of AMPK-related kinase MPK38/MELK leads to male-specific obesity in aged mature adult mice

Murine protein serine-threonine kinase 38 (MPK38)/maternal embryonic leucine zipper kinase (MELK) is implicated in diverse biological processes, including the cell cycle, apoptosis, and tumorigenesis; however, its physiological role is unknown. Using mice lacking MPK38 (MPK38^−/−), we found that MPK38^−/− male, but not female, mice (7 months of age) became obese while consuming a standard diet, displayed impairments in metabolism and inflammation, became obese than wild-type mice while consuming a high-fat diet (HFD), and exhibited no castration/testosterone (T) replacement-induced metabolic changes. The adenoviral restoration of MPK38 ameliorated the obesity-induced adverse metabolic profile of the obese male, but not female, mice. Seven-month-old MPK38^−/− males displayed typical post-castration concentrations of serum testosterone with an accompanying decrease in serum luteinizing hormone (LH) levels, suggesting a role for MPK38 in the age-related changes in serum testosterone in aged mature adult male mice. The stability and activity of MPK38 were increased by dihydrotestosterone (DHT) but reduced by estradiol (E2). These findings suggest MPK38 as a therapeutic target for obesity-related metabolic disorders in males.