Adropin promotes testicular functions by modulating redox homeostasis in adult mouse.

PURPOSE: Adropin is an emerging metabolic hormone that has a role in regulating energy homeostasis. The present study aimed to explore the impact of adropin on redox homeostasis and its possible role in testicular functions in adult mouse testis. METHODS: Western blot, flow-cytometry, and TUNEL assay were performed to explore the impact of intra-testicular treatment of adropin (0.5 µg/testis) on testicular functions of adult mice. Hormonal assay was done by ELISA. Further, antioxidant enzyme activities were measured. RESULTS: Adropin treatment significantly increased the sperm count and testicular testosterone by increasing the expression of GPR19 and steroidogenic proteins. Also, adropin treatment reduced the oxidative/nitrosative stress by facilitating the translocation of NRF2 and inhibiting NF-κB into the nucleus of germ cells. Enhanced nuclear translocation of NRF2 leads to elevated biosynthesis of antioxidant enzymes, evident by increased HO-1, SOD, and catalase activity that ultimately resulted into declined LPO levels in adropin-treated mice testes. Furthermore, adropin decreased nuclear translocation of NF-κB in germ cells, that resulted into decreased NO production leading to decreased nitrosative stress. Adropin/GPR19 signaling significantly increased its differentiation, proliferation, and survival of germ cells by elevating the expression of PCNA and declining caspase 3, cleaved caspase 3 expression, Bax/Bcl2 ratio, and TUNEL-positive cells. FACS analysis revealed that adropin treatment enhances overall turnover of testicular cells leading to rise in production of advanced germ cells, notably spermatids. CONCLUSION: The present study indicated that adropin improves testicular steroidogenesis, spermatogenesis via modulating redox potential and could be a promising target for treating testicular dysfunctions.

Restoration of the soil fertility under Cr(VI) and artificial drought condition by the utilization of plant growth-promoting Bacillus spp. SSAU2.

The study explores the potential of an indigenous halo-tolerant microbe identified as Bacillus spp. SSAU-2 in enhancing soil fertility and promoting plant growth for sustainable agricultural practices under the influence of multiple abiotic stresses such as Cr(VI), high salinity, and artificial drought condition. The study investigated various factors influencing IAA synthesis by SSAU-2, such as pH (5 to 11), salinity (10 to 50 g/L), tryptophan concentration (0.5 to 1%), carbon (mannitol mand lactose), and nitrogen sources (peptone and tryptone). The highest IAA concentration was observed at pH 10 (1.695 mg/ml) and pH 11 (0.782 mg/ml). IAA synthesis was optimized at a salinity level of 30 g/l, with lower and higher salinity levels resulting in decreased IAA concentrations. Notably, the presence of mannitol and lactose significantly augmented IAA synthesis, while glucose and sucrose had inhibitory effects. Furthermore, peptone and tryptone played a pivotal role in enhancing IAA synthesis, while ammonium chloride exerted an inhibitory influence. SSAU-2 showed a diverse array of capabilities, including the synthesis of gibberellins, extracellular polymeric substances, siderophores, and hydrogen cyanide along with nitrogen fixation and ammonia production. The microbe could efficiently tolerate 45% PEG-6000 concentration and effectively produce IAA in 15% PEG concentration. It could also tolerate high concentration of Cr(VI) and synthesize IAA even in 50 ppm Cr(VI). The findings of this study provide valuable insights into harnessing the potential of indigenous microorganisms to promote plant growth, enhance soil fertility, and establish sustainable agricultural practices essential for restoring the health of ecosystems.

Adropin may regulate ovarian functions by improving antioxidant potential in adult mouse.

The corpus luteum (CL) is a temporary endocrine gland that synthesizes progesterone. The luteal progesterone plays a central role in the regulation of the estrous cycle as well as the implantation and maintenance of pregnancy. Our previous study showed the expression of adropin and its receptor, GPR19, in the luteal cells and its significant role in luteinization. The aim of the present study was to investigate the in vitro effect of adropin on hCG-induced ovarian functions in adult mice. We also evaluated the effect of exogenous treatment with adropin on ovarian steroidogenesis and anti-oxidant parameters, with special emphasis on CL function. Our results demonstrated that adropin acts synergistically with hCG to promote ovarian steroidogenesis and survival by increasing the expression of StAR, 3ß-HSD, and aromatase proteins and decreasing the BAX/BCL2 ratio. Exogenous adropin treatment increased progesterone production by increasing the expression of GPR19, StAR and 3ß-HSD enzymes in the mouse ovary. Also, adropin inhibited the luteal oxidative stress by increasing nuclear translocation of NRF-2 in CL, which resulted in increased HO-1 expression and SOD, catalase activity. Decreased oxidative stress might inhibit the translocation of NF-κB into the nucleus of luteal cells, resulting into increased survival and decreased apoptosis, as evident by decreased lipid peroxidation, BAX/BCL2 ratio, caspase 3, active caspase 3 expression, and TUNEL-positive cells in adropin treated mice. Our findings suggest that adropin can be a promising candidate that can enhance the survivability of the CL.

Discrepancies in Gleason score between needle core biopsy and radical prostatectomy specimens with correlation between clinical and pathological staging.

BACKGROUND: The studies have shown that GS given after assessment of the entire prostate gland on the radical prostatectomy specimen may differ from GS given after examination of a small sample from needle core biopsy. We conducted this study to assess discrepancies in the Gleason score between NCB and RP specimens and to find out the correlation between the clinical stage and pathological stage. METHODS: The study included 174 patients with carcinoma prostate which underwent robotic-assisted radical prostatectomy (RARP). Pre-operative Gleason score was determined on 12-core biopsy samples under trans-rectal ultrasound (TRUS) guidance. The Gleason score obtained from the radical prostatectomy specimen was compared with that of the NCB Gleason score to find out differences. RESULTS: The preoperative Gleason score (GS) ranges from 6 to 9 with a mean GS of 6.97 ± 1.02. The post-operative GS ranges between 6 and 10 with mean and GS of 7.5 ± 1.10. On the pre-operative assessment of biopsy specimens, 70 (43.2%) patients had a GS of 6, while 44 patients had a GS of 7 (27.1%) and 48 (29.8%) patients had a GS of more than 7. On the postoperative assessment of specimens, 31 (19.1%) patients had post-operative GS of 6, while 66 (41%) patients had GS of 7 and 74 (41.1%) patients had GS of more than 7. When pre-operative GS and post-operative GS were compared, no changes were observed in the GS of 79 patients, whereas 83 patients showed the difference in GS, with 75 patients showing up-gradation and eight patients marked as down-graded. CONCLUSION: concordance between biopsy and the pathology results directly affects the prognosis of the patient. The results of our study demonstrated the rate of discordance between Gleason scores obtained from transrectal prostate biopsy and RP surgical specimens. This rate brings into question the accuracy of the chosen treatment.

Incidental detection of rare vascular variation during pyeloplasty and its clinical implication - A case report.

ABSTRACT: Crossing vessels is one of the important causes of pelviureteric junction obstruction (PUJO). Accessory lower polar vessels are commonly seen with congenital PUJO, but they are not always the cause of obstruction. We incidentally encountered a variation in the lower polar crossing vessel while doing laparoscopic pyeloplasty in a patient with congenital PUJO. We encountered a right accessory lower polar artery and vein along with a right gonadal artery arising from the accessory right renal artery and right gonadal vein draining into the right lower polar crossing accessory renal vein. Knowledge of variations in genitourinary vasculature is important in the current era to prevent inadvertent complications.

From A to E: Uniting vitamins against stroke risk-A systematic review and network meta-analysis.

BACKGROUND AND AIM: Stroke represents a significant public health challenge, necessitating the exploration of preventive measures. This network meta-analysis aimed to assess the efficacy of different vitamin treatments compared to a placebo in preventing stroke. METHODS: A systematic electronic search in databases including PubMed, EmBASE, Web of Science, clinicaltrials.gov, and Google Scholar until 31 May 2023 was conducted, to identify published studies investigating the association between vitamin intake and the risk of stroke. Pooled risk ratio (RR) with 95% confidence intervals (CIs) was calculated using a frequentist network meta-analysis. Furthermore, we ranked vitamins based on p-scores, facilitating a comparative assessment of their effectiveness in preventing stroke. RESULTS: A total of 56 studies, including 17 randomized controlled trials (RCTs) and 39 cohort studies were analyzed. Direct estimates obtained from network meta-analysis, we found that vitamin A (RR: .81 [.72-.91]), vitamin B-complex (RR: .85 [.74-.97]), vitamin B6 (RR: 79 [.68-.92]), folate (RR: .86 [.75-.97]), vitamin C (RR: .77 [.70-.85]) and vitamin D (RR: .73 [.64-.83]) were significantly associated with a decreased stroke risk. However, no significant association was observed for vitamin B2, vitamin B12, and vitamin E. Subsequent to network meta-analysis, vitamins were ranked in decreasing order of their efficacy in stroke prevention based on p-score, with vitamin D (p-score = .91), vitamin C (p-score = .79), vitamin B6 (p-score = .70), vitamin A (p-score = .65), vitamin B-complex (p-score = .53), folate (p-score = .49), vitamin B2 (p-score = .39), vitamin E (p-score = .28), vitamin B12 (.13) and placebo (.10). CONCLUSION: Our study has established noteworthy connections between vitamin A, vitamin B-complex, vitamin B6, folate, vitamin C, and vitamin D in the realm of stroke prevention. These findings add substantial weight to the accumulating evidence supporting the potential advantages of vitamin interventions in mitigating the risk of stroke. However, to solidify and validate these observations, additional research is imperative. Well-designed clinical trials or cohort studies are needed to further explore these associations and formulate clear guidelines for incorporating vitamin supplementation into effective stroke prevention strategies.

Early port site and peritoneal metastasis following robot-assisted radical cystectomy: a rare case report.

Radical cystectomy with pelvic lymph node dissection is the recommended treatment for managing muscle-invasive carcinoma of the urinary bladder. Early recurrence is observed in only about 4.1% of cases. Port-site metastasis following robot-assisted radical cystectomy is extremely rare. We encountered a challenging and a rare case of bladder cancer that manifested with port-site and peritoneal metastasis within 6 weeks of surgery.

Adropin, a novel hepatokine: localization and expression during postnatal development and its impact on testicular functions of pre-pubertal mice.

Adropin, a multifaceted peptide, was identified as a new metabolic hormone responsible for regulating gluco-lipid homeostasis. However, its role in the testicular function is not yet understood. We aimed to investigate the localization and expression of adropin and GPR19 during different phases of postnatal development. Immunohistochemical study revealed the intense reactivity of adropin in the Leydig cells during all phases of postnatal development, while GPR19 showed intense immunoreactivity in the pachytene spermatocytes and mild immunoreactivity in Leydig cells as well as primary and secondary spermatocytes. Western blot study revealed maximum expression of GPR19 in pre-pubertal mouse testis that clearly indicates maximum responsiveness of adropin during that period. So, we hypothesized that adropin may act as an autocrine/paracrine factor that regulates pubertal changes in mouse testis. To examine the effect of adropin on pubertal onset, we gave bilateral intra-testicular doses (0.5 and 1.5 µg/testis) to pre-pubertal mice. Adropin treatment promoted testicular testosterone synthesis by increasing the expression of StAR, 3ß-HSD, and 17ß-HSD. Adropin also promoted germ cell survival and proliferation by upregulating the expression of PCNA and downregulating the Bax/Bcl2 ratio and Caspase 3 expression resulting in fewer TUNEL-positive cells in adropin-treated groups. FACS analysis demonstrated that adropin treatment not only increases 1C to 4C ratio but also significantly increases the 1C (spermatid) and 1C to 2C ratio which demarcates accelerated germ cell differentiation and turnover of testicular cells. In conclusion, adropin promotes steroidogenesis, germ cell survival, as well as the proliferation in the pre-pubertal mouse testis that may hasten the pubertal transition in an autocrine/paracrine manner.

Assessing pentafecta outcomes post radical cystectomy: A tertiary care center study.

INTRODUCTION: Bladder cancer is a common and serious disease globally, often requiring radical cystectomy as the preferred treatment. However, this procedure carries substantial risks and complications. To evaluate its success, pentafecta, a five-component measure, was introduced. This study investigates the attainment of pentafecta following radical cystectomy and examines factors that influence its achievement. METHODOLOGY: This retrospective, single-group study was conducted at AIIMS Jodhpur. The study population included 42 patients who underwent radical cystectomy for bladder cancer. Various data, including demographic characteristics, clinical features, surgical techniques, and postoperative outcomes, were collected from medical records. The primary outcome measure was the rate of achieving pentafecta, which comprises five parameters. RESULTS: Out of 42 patients, 26 (61.9%) achieved pentafecta. Age, gender, comorbidities and surgical approach did not significantly affect the attainment of pentafecta. Negative surgical margins were achieved in 95.2% of cases, and adequate lymph node dissection (>16 lymph nodes) was performed in 85.7% of cases. The absence of Clavien-Dindo grade 3-5 complications and recurrence was observed in 80.9% and 90.47% of cases, respectively. Uretero-enteric stricture was absent in 95.2% of cases. CONCLUSION: The study emphasizes the significance of negative surgical margins, thorough lymph node dissection, absence of complications, recurrence, and uretero-enteric strictures in evaluating the success of radical cystectomy as pentafacta outcomes. Patients with higher drain output and wound infections are less likely to achieve pentafacta outcome and indicates poorer outcome. By considering these factors, clinicians can assess patient outcomes and identify areas for improvement.

Correlation of urinary continence recovery with various factors after Robot assisted radical prostatectomy.

BACKGROUND: In addition to ensuring cancer control, prevention of incontinence which significantly impact patients' quality of life, is also an important issue in robot-assisted radical prostatectomy (RARP) operations. In this study, we aimed to find the correlation of urinary continence recovery with various factors after Robot assisted radical prostatectomy. METHODS: This study included 162 patients treated with RARP with perioperative data and at least 1 year of follow-up. Also, the preoperative, intraoperative, and postoperative parameters of the patients were analyzed. The continence recovery rate in our study was assessed at 6th week, 3rd month, 6th month, 9th month, and 12th month, post-surgery. Logistic regression analysis evaluated the association between the predictive factors and urinary continence recovery in the early and late stages. RESULTS: The majority of patients with prostate cancer present in sixth decade of life. The majority of our patients (56.7%) were categorized as high risk using D'Amico classification. The continence rate in our study at 6th week, 3rd month, 6th month, 9th month, and 12th month were 40.1%, 72.2%, 85.2%, 89.5%, and 91.4%, respectively. No improvement in continence status was observed after 1 year in our study. There was significant correlation of age with continence status at 6th week, 3rd month, and 6th month. The young age is associated with early recovery of continence. At 3 and 9 months, the non-diabetics cases achieved significantly higher continence rates than diabetics (p < 0.05) which shows that diabetes causes delay in attainment of continence. CONCLUSION: The young age may be associated with early recovery of continence, but further validation requires large number of cases. We attributed good continence recovery rate to meticulous dissection and preservation of good urethral length.

Mucosal SARS-CoV-2 vaccination of rodents elicits superior systemic T central memory function and cross-neutralising antibodies against variants of concern.

BACKGROUND: COVID-19 vaccines used in humans are highly effective in limiting disease and death caused by the SARS-CoV-2 virus, yet improved vaccines that provide greater protection at mucosal surfaces, which could reduce break-through infections and subsequent transmission, are still needed. METHODS: Here we tested an intranasal (I.N.) vaccination with the receptor binding domain of Spike antigen of SARS-CoV-2 (S-RBD) in combination with the mucosal adjuvant mastoparan-7 compared with the sub-cutaneous (S.C.) route, adjuvanted by either M7 or the gold-standard adjuvant, alum, in mice, for immunological read-outs. The same formulation delivered I.N. or S.C. was tested in hamsters to assess efficacy. FINDINGS: I.N. vaccination improved systemic T cell responses compared to an equivalent dose of antigen delivered S.C. and T cell phenotypes induced by I.N. vaccine administration included enhanced polyfunctionality (combined IFN-γ and TNF expression) and greater numbers of T central memory (TCM) cells. These phenotypes were T cell-intrinsic and could be recalled in the lungs and/or brachial LNs upon antigen challenge after adoptive T cell transfer to naïve recipients. Furthermore, mucosal vaccination induced antibody responses that were similarly effective in neutralising the binding of the parental strain of S-RBD to its ACE2 receptor, but showed greater cross-neutralising capacity against multiple variants of concern (VOC), compared to S.C. vaccination. I.N. vaccination provided significant protection from lung pathology compared to unvaccinated animals upon challenge with homologous and heterologous SARS-CoV-2 strains in a hamster model. INTERPRETATION: These results highlight the role of nasal vaccine administration in imprinting an immune profile associated with long-term T cell retention and diversified neutralising antibody responses, which could be applied to improve vaccines for COVID-19 and other infectious diseases. FUNDING: This study was funded by Duke-NUS Medical School, the Singapore Ministry of Education, the National Medical Research Council of Singapore and a DBT-BIRAC Grant.

Adropin may promote insulin stimulated steroidogenesis and spermatogenesis in adult mice testes.

Adropin is a versatile peptide which was discovered as a novel metabolic hormone that is involved in the regulation of lipid and glucose homeostasis. However, its possible role in the testicular function is not yet understood. The aim of our study was to explore the distribution pattern of adropin and GPR19 in various cell types and its possible role in testicular functions of adult mice. Immunohistochemical study revealed the intense immunoreactivity of adropin in the Leydig cells, while GPR19 showed intense immunoreactivity in the pachytene spermatocytes and mild immunoreactivity in Leydig cells and primary as well as secondary spermatocytes in mouse testis. Enho mRNA was also found to be expressed in the mouse testis. These findings suggested that adropin-GPR19 signaling may act in autocrine/paracrine manner to modulate testicular functions. Furthermore, to find out the direct role of adropin in the testicular function, in vitro study was performed in which testicular slices were cultured with adropin alone (10 and 100 ng/mL) and in combination with insulin (5 µg/mL). Adropin alone inhibited testicular testosterone synthesis by inhibiting the expression of P450-SCC, 3ß-HSD, and 17ß-HSD while along with insulin stimulated the testicular testosterone synthesis by increasing the expression of GPR19, IR, StAR, P450-SCC, 3ß-HSD, and 17ß-HSD. Adropin alone or in combination with insulin promoted germ cell survival and proliferation by upregulating the expression of PCNA, Bcl2, and pERK1/2. Thus, it can be concluded that adropin-GPR19 signaling promotes insulin stimulated steroidogenesis and germ cell survival as well as proliferation in the mice testes in an autocrine/paracrine manner.

Postradical cystectomy delayed urethral recurrence: a rare presentation posing diagnostic dilemma.

The incidence of urethral recurrence after radical cystectomy is 1% to 8%, with most cases occurring within the first 2 years of surgery. Prophylactic urethrectomy is rarely performed nowadays due to no known survival benefit and increased morbidity due to the procedure. However, we encountered a rare case of delayed urethral recurrence presenting as recurrent urethral collection 4 years after radical cystectomy with ileal conduit diversion, posing a diagnostic dilemma.

Large Urethral Diverticular Calculus Clinically Mimicking a Metastatic Deposit in a Case of Ovarian Mass.

Calculus in the urethra of the female is very unusual. The patient remains asymptomatic or uncommonly presents with symptoms of dysuria, post-void urinary dribbling, and dyspareunia. If asymptomatic, it can be diagnosed incidentally on gynecological examination. Being hard in consistency, it may mimic metastatic lesion. We present a case of a female who presented to us for management of ovarian mass. On routine examination there was a hard mass in her vagina which was suspected to be a metastatic lesion. This mass on evaluation came out to be a urethral diverticulum with a large calculus. Very large urethral calculus are a very rare presentation in a female.

SARS-CoV-2 ORF6 protein targets TRIM25 for proteasomal degradation to diminish K63-linked RIG-I ubiquitination and type-I interferon induction.

Evasion and antagonism of host cellular immunity upon SARS-CoV-2 infection provide replication advantage to the virus and contribute to COVID-19 pathogenesis. We explored the ability of different SARS-CoV-2 proteins to antagonize the host's innate immune system and found that the ORF6 protein mitigated type-I Interferon (IFN) induction and downstream IFN signaling. Our findings also corroborated previous reports that ORF6 blocks the nuclear import of IRF3 and STAT1 to inhibit IFN induction and signaling. Here we show that ORF6 directly interacts with RIG-I and blocks downstream type-I IFN induction and signaling by reducing the levels of K63-linked ubiquitinated RIG-I. This involves ORF6-mediated targeting of E3 ligase TRIM25 for proteasomal degradation, which was also observed during SARS-CoV-2 infection. The type-I IFN antagonistic activity of ORF6 was mapped to its C-terminal cytoplasmic tail, specifically to amino acid residues 52-61. Overall, we provide new insights into how SARS-CoV-2 inhibits type-I IFN induction and signaling through distinct actions of the viral ORF6 protein.

18F-fluoro-2-deoxy-2-d-glucose PET-CT (FDG PET-CT) in staging of high-risk renal and urothelial bladder cancers (COPPER-T) trial protocol.

Background and Study Design: Role of 18F-fluoro-2-deoxy-2-d-glucose positron emission tomography-computed tomography (FDG PET-CT) in evaluation of renal cell cancers (RCC) and urinary bladder cancers is not standardized, and the COPPER-T trial, which is a single centre prospective randomized study, was designed to compare it with conventional imaging for staging of clinically localized high risk RCC and urinary bladder carcinoma (Stage T2 and above). Patients and Methods: There will be two subgroups of patients: RCC and urinary bladder carcinoma. In each of these, the patients will be randomized to either Arm A or Arm B. In each of the arms, each patient will be subjected to diagnostic imaging by FDG PET-CT. The CT scan will be a contrast-enhanced scan like that in conventional staging. A radiologist and nuclear medicine specialist will report the scan independently. The radiologist will not have access to the PET scan sequences and will only review the contrast-enhanced computed tomography (CECT) images. In Arm A, the report of the conventional imaging modality, that is, CECT and bone scan if done, will be reviewed first by the clinician, and based on this report, a management plan will be made. Then, the PET-CT report will be reviewed, and change in the management plan will be noted. New findings or equivocal findings if any in the PET-CT report would be noted. In Arm B, the report of the PET-CT report will be reviewed first by the clinicians, and a management plan will be made. Then, the CECT and/or bone scan reports will be reviewed, and any change in the management plan will be noted. Outcome and Significance: Final analysis of the data after completion of the trial will help in clarifying the role of FDG PET-CT in high risk RCC and transitional cell carcinoma (TCC) of the bladder, its diagnostic accuracy compared with conventional imaging and the impact of using it on patient management.

Palladium(II)-Catalyzed Decarboxylative Difunctionalization of Alkynoic Acids To Access (E)-ß-Sulfonylacrylamides and DFT Study.

A palladium(II)-catalyzed regio- and stereoselective difunctionalization of alkynoic acids has been achieved using sodium sulfinates and isocyanides to synthesize (E)-ß-sulfonylacrylamides. The reaction proceeds via decarboxylative isocyanide addition, followed by sulfonylation. This three-component process works well with aromatic, heteroaromatic, and aliphatic alkynoic acids with good functional group tolerance and excellent regio- and stereoselectivity. DFT calculations were carried out to explain the reaction mechanism and the stereoselective formation of (E)-ß-sulfonylacrylamides.

Ontogeny of adropin and its receptor expression during postnatal development and its pro-gonadal role in the ovary of pre-pubertal mouse.

Adropin, a highly conserved multifunctional peptide hormone, has a beneficial effect on the maintenance of gluco-lipid homeostasis, endothelial and cardiovascular functions. However, the expression and potential role of adropin in ovarian function are not fully elucidated. The present study aimed to investigate the expression of adropin and GPR19 in the mice ovary during various stages of postnatal development. This study also explored whether the treatment of adropin can modulate the timing of puberty, for which pre-pubertal mice were treated with adropin. The result showed the intense immunoreactivity of adropin in TICs, while GPR19 immunoreactivity was noted in GCs in infantile, pre-pubertal, and pubertal mice ovary. Also, adropin and GPR19 are highly expressed in the CL of the ovary of reproductively active mice. The fact that adropin expression in the ovary at different stages of postnatal development positively correlated with circulating progesterone and estradiol indicated that it has a role in the production of steroid hormones. Furthermore, the results of in vivo studies in pre-pubertal mice showed that adropin promotes early folliculogenesis by enhancing the proliferation (PCNA) of GCs of cortical ovarian follicles and promotes estradiol production by enhancing the expression of GPR19, StAR, CYP11A1 and aromatase proteins. Also, adropin treatment increases the Bax/Bcl2 ratio and expression of cleaved caspase-3 and ERα proteins, which may result in increased apoptosis of medullary follicles leading to the formation of a well-developed interstitium with interstitial glandular cells. Collectively, these findings indicate that adropin may be a factor that accelerates pubertal development in the ovary and could be utilized as a therapeutic approach for treating pubertal delay.

Adropin may regulate corpus luteum formation and its function in adult mouse ovary.

BACKGROUND: Adropin, a unique peptide hormone, has been associated with the regulation of several physiological processes, including glucose homeostasis, fatty acid metabolism, and neovascularization. However, its possible role in ovarian function is not understood. Our objective was to examine the expression of adropin and its putative receptor, GPR19, in the ovaries of mice at various phases of the estrous cycle. METHODS: Immunohistochemistry and western blot analysis were performed to explore the localization and changes in expression of adropin and GPR19 in the ovaries during different phases of the estrous cycle in mice. Hormonal assays were performed with ELISA. An in vitro study was performed to examine the direct effect of adropin (10, 100 ng/ml) on ovarian function. RESULTS: A western blot study showed that adropin and GPR19 proteins were maximum during the estrus phase of the estrous cycle. Interestingly, adropin and GPR19 displayed intense immunoreactivity in granulosa cells of large antral follicles and corpus luteum. This suggested the possible involvement of adropin in corpus luteum formation. Adropin treatment stimulated progesterone synthesis by increasing GPR19, StAR, CYP11A1, and 3ß-HSD expressions, while it decreased estrogen synthesis by inhibiting 17ß-HSD and aromatase protein expressions. Moreover, adropin treatment upregulated the cell cycle arrest-CDK inhibitor 1B (p27kip1), pERK1/2, and angiogenic protein (EG VEGF) that are involved in the process of luteinization. CONCLUSIONS: Adropin GPR19 signaling promotes the synthesis of progesterone and upregulates the expression of p27kip1, EG VEGF, and erk1/2, resulting in cell cycle arrest and neovascularization, which ultimately leads to corpus luteum formation.