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Introduction: Polyaromatic hydrocarbons (PAHs) are considered as redox active environmental toxicants inducing oxidative stress (OS) mediated injury to cells. Oxidative predominance is reported in 30%-80% of idiopathic male infertility (IMI) patients. Hence, this work aims to unravel correlation, if any, between seminal PAH exposome and sperm function in IMI patients through a proteomic approach. Methods: Seminal PAH exposome was analyzed in 43 fertile donors and 60 IMI patients by HPLC and receiver operating characteristic (ROC) curve was applied to find out the cut-off limits. Spermatozoa proteome was analyzed by label free liquid chromatography mass spectroscopy (LC-MS/MS) followed by molecular pathway analysis using bioinformatic tools. Validation of key proteins' expression and protein oxidative modifications were analyzed by western blot. Results and discussion: Of the 16 standards toxic PAH, 13 were detected in semen. Impact of the different PAHs on fertility are Anthracene < benzo (a) pyrene < benzo [b] fluoranthene < Fluoranthene < benzo (a) anthracene ROC). Benzo [a] pyrene is invariably present in all infertile patients while naphthalene is present in both groups. Of the total 773 detected proteins (Control: 631 and PAH: 717); 71 were differentially expressed (13 underexpressed, 58 overexpressed) in IMI patients. Enrichment analysis revealed them to be involved in mitochondrial dysfunction and oxidative phosphorylation, DNA damage, Aryl hydrocarbon receptor (AHR) signaling, xenobiotic metabolism and induction of NRF-2 mediated OS response. Increased 4-hydroxynonenal and nitrosylated protein adduct formation, and declined antioxidant defense validates induction of OS. Increased GSH/GSSG ratio in patients may be an adaptive response for PAH metabolism via conjugation as evidenced by over-expression of AHR and Heat shock protein 90 beta (HSP90β) in patients. Seminal PAH concentrations, particularly benzo (a) pyrene can be used as a marker to distinguish IMI from fertile ones with 66.67% sensitivity and 100% specificity (95% confidence interval) along with oxidative protein modification and expression of AHR and HSP90β.

Bi-directional crosstalk between Ca2+ signaling and ROS modulates physiological processes as a part of a regulatory circuit including sperm function. The role of transient receptor potential vanilloid 1 (TRPV1) in this regard cannot be undermined. This is the first report demonstrating the Ca2+-sensitive TRPV1 channel to be under-expressed in spermatozoa of subfertile men, idiopathic infertile men, and normozoospermic infertile males with high ROS (idiopathic infertility and unilateral varicocele). To study the effect of TRPV1 in determining the fertility outcome, we compared the expression profile of TRPV1 in spermatozoa of male partners who achieved pregnancy by natural conception (NC+, n = 10), IVF (IVF+, n = 23), or ICSI (ICSI +, n = 9) and their respective counterparts with failed pregnancy NC (n = 7), IVF (n = 23), or ICSI (n = 10), by both immunocytochemistry and flow-cytometry. Reduced expression of TRPV1 in sperm of IVF ± and ICSI ± men with respect to that NC+ men imply its role in mediating successful fertilization. Unsuccessful pregnancy outcome with an underexpression of TRPV1 in sperm of NC-/IVF-/ICSI-men suggests its role in conception and maintenance of pregnancy. Since ROS is regarded as one of the major contributors to sperm dysfunction, the effect of H2O2 +/- TRPV1 modulators (RTX/iRTX) on acrosomal reaction and calcium influx was evaluated to confirm TRPV1 as a redox sensor in human sperm. A significant increment in the percentage of acrosome reacted spermatozoa along with augmented Ca2+-influx was observed after H2O2 treatment, both in the presence or absence of TRPV1 agonist resiniferatoxin (RTX). The effect was attenuated by the TRPV1 antagonist iodoresiniferatoxin (iRTX), indicating the involvement of TRPV1 in mediating H2O2 response. Enhancement of motility and triggering of acrosomal reaction post TRPV1 activation suggested that disruption of these signaling cascades in vivo, possibly due to down-regulation of TRPV1 in these subfertile males. Bioinformatic analysis of the crosstalk between TRPV1 with fertility candidate proteins (reported to influence IVF outcome) revealed cell death and survival, cellular compromise, and embryonic development to be the primary networks affected by anomalous TRPV1 expression. We therefore postulate that TRPV1 can act as a redox sensor, and its expression in spermatozoa may serve as a fertility marker.

Two triazine‐cored BODIPY trimers (Compounds 6 and 12) were synthesized and well characterized using 1H NMR, 13C NMR, 11B NMR, 19F NMR, FT‐IR, and high‐resolution mass spectral analysis. The photophysical, computational, and in vitro anticancer studies of the synthesized compounds were comprehensively evaluated along with previously reported phenylene‐BODIPY trimer (Compound 1). The photophysical studies indicated that the triazine‐cored BODIPY trimers exhibited a slight bathochromic shift compared to the phenylene‐cored trimer. Density functional theory (DFT) calculations suggest that the order of stability of the BODIPY trimers was 1 > 6 > 12. The anticancer efficacy of the BODIPY trimers was investigated against human breast adenocarcinomas cell line MDA‐MB‐231 and mouse embryo fibroblast cell line NIH/3T3 through in vitro cytotoxicity assay. All the BODIPY trimers exhibited elevated cytotoxicity towards cancer cells while displaying lesser cytotoxicity towards normal cells. Compound 6 showed the highest cell death potential with an IC50 value of 27.02 μM, which is twice higher than that of the chemotherapeutic drug cisplatin. The triazine‐cored BODIPY trimers demonstrated superior cytotoxicity against cancer cells in comparison to their phenylene‐cored counterparts. The enhanced cytotoxicity of the triazine‐cored trimers suggests that the triazine core plays a crucial role in enhancing their therapeutic efficacy. This result underscores the potential of triazine‐cored BODIPY trimers as promising anticancer agents. [ABSTRACT FROM AUTHOR]

Effect of priming on the maturation and spawning were tested in two fish species using gonadotropin-releasing hormone (GnRH), carp pituitary homogenate (CPH) and clomiphene citrate (clomid). The fish were injected with a dose of GnRH, CPH and clomid, calibrated to contain 0.3ml/kg, 7 mg/kg and 70mg/kg respectively in three split doses (two priming doses and one final dose). Two priming doses enhanced the maturation and spawning in fish as evident from hormone assay, histology and gamete analysis. Among the inducing agents, two priming doses of GnRH showed 94% maturation and higher GSI (5.31♂;18.5♀) than CPH and clomid injected rohu. Subsequently, successful spawning recorded supported by elevated levels of FSH and LH in blood. Priming with CPH and clomid showed better maturation rate than GnRH injected Nile tilapia. The sperm count of tilapia administered with CPH and clomid was 3.7±0.72×109 and 4.1±0.86×109 respectively. The efficacy of hormonal priming in synchronising the gamete development in rohu and tilapia was further evident from the increased number of synchronised oocyte development. This study may help in developing strategies for broodstock and hatchery management of carps and tilapias. [ABSTRACT FROM AUTHOR]

In this study, we report the cardioprotective effect of the glycerol monooleate (GMO) based nanocurcumin in both in vitro and in vivo conditions under a hyperthyroid state. The heart is one of the primary target organs sensitive to the action of thyroid hormone, and slight variations in the thyroid hormone serum concentrations result in measurable changes in cardiac performance. Hyperthyroidism‐induced hypermetabolism is associated with oxidative stress and is an important mechanism responsible for the progression of heart failure. Curcumin has been known to play a protective role against oxidative stress‐related diseases like Alzheimer's, asthma, and aging due to its antioxidant properties. Nevertheless, its potent biological activity has been hindered due to its poor bioavailability. To overcome this drawback, a GMO‐based biodegradable nanoparticle (NP) formulation loaded with curcumin has been developed, and the protective effect of curcumin‐loaded NPs was compared against the native drug. Oxidative stress parameters like reactive oxygen species (ROS) release, change in mitochondrial membrane permeability, lipid peroxidation (LPx), lactate dehydrogenase (LDH) release, and the activity and protein expression of the endogenous antioxidant enzymes like superoxide dismutase, catalase (CAT) and glutathione peroxidase were evaluated. The results from in vitro showed that curcumin‐loaded NPs showed better DPPH and NO radical scavenging activity than native curcumin in a concentrations range of 2.5–20 µM. It was also observed that the nanoparticulate curcumin was comparatively more effective than native curcumin in protecting against ROS‐induced membrane damage by reducing LPx and LDH leakage at low concentrations of 5–10 µM. Further, curcumin NPs performed better in facilitating the activities of antioxidant enzymes under in vitro and in vivo conditions with respect to time and concentrations, resulting in reduced cellular ROS levels. In this scenario, we anticipate that curcumin‐loaded NPs can serve as a better antioxidant than its native counterpart in protecting the heart from oxidative stress‐related diseases. Significance Statement: Our research presents the cardioprotective effect of glycerol monooleate (GMO) based nano‐curcumin in vitro and in vivo conditions during a hyperthyroid state. The study found that nanoparticulate curcumin outperformed native curcumin in shielding against oxidative stress in both in vitro and in vivo settings, leading to decreased cellular ROS levels over time and at varying concentrations. [ABSTRACT FROM AUTHOR]

Introduction It is textbook knowledge that spermatogenesis is impossible without luteinizing hormone-stimulated (LH-stimulated) testicular testosterone (T) production (1, 2). Human mutations and genetically modified mice provide further proof for this, [...], Spermatogenesis is regulated by the 2 pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). This process is considered impossible without the absolute requirement of LH-stimulated testicular testosterone (T) production. The role of FSH remains unclear because men and mice with inactivating FSH receptor (FSHR) mutations are fertile. We revisited the role of FSH in spermatogenesis using transgenic mice expressing a constitutively strongly active FSHR mutant in a LH receptor-null (LHR-null) background. The mutant FSHR reversed the azoospermia and partially restored fertility of [Lhr.sup.-/-] mice. The finding was initially ascribed to the residual Leydig cell T production. However, when T action was completely blocked with the potent antiandrogen flutamide, spermatogenesis persisted. Hence, completely T-independent spermatogenesis is possible through strong FSHR activation, and the dogma of T being a sine qua non for spermatogenesis may need modification. The mechanism for the finding appeared to be that FSHR activation maintained the expression of Sertoli cell genes considered androgen dependent. The translational message of our findings is the possibility of developing a new strategy of high- dose FSH treatment for spermatogenic failure. Our findings also provide an explanation of molecular pathogenesis for Pasqualini syndrome (fertile eunuchs; LH/T deficiency with persistent spermatogenesis) and explain how the hormonal regulation of spermatogenesis has shifted from FSH to T dominance during evolution.

Introducción: Los tumores ováricos son raros en la edad pediátrica y representan del 1 al 5% de los tumores infantiles. El objetivo del presente trabajo es conocer cuáles son los tumores de ovario más frecuentes en nuestro medio en niñas y adolescentes en un centro oncológico de la ciudad de Guayaquil-Ecuador. Métodos: El presente estudio es descriptivo y retrospectivo, en la que se realiza una revisión de registros de niñas y adolescentes con diagnóstico de tumores de ovario, en el Instituto Oncológico Nacional “Dr. Juan Tanca Marengo” en el período de enero 2015 a mayo del 2017. Las variables registradas fueron edad, diagnóstico ecográfico, diagnostico histopatológico, ovario afecto, características clínicas, salpingectomía, marcadores tumorales. Se utiliza estadística descriptiva. Resultados: Ingresaron al estudio 32 pacientes de 12.7 años promedio. El ovario más afectado fue el derecho con una relación 2.2: 1 y en 9 % fue bilateral. La histología reportada de los quistes serosos fueron el 21 % quiste folicular y 18.5 % por quiste lúteo. Los quistes simples representaron el 15.25 %, el cistoadenoma y el teratoma maduro con un 9 %, el quiste dermoide y le endometrioma con un 3 %. El dolor fue el síntoma más llamativo estado como síntoma único en 65.5 %. El 18.75 % terminó en anexectomía con ooforectomía por extensión del quiste, el 81.25 % solo requirió quistectomía. Conclusión: La histología reportada en esta serie de tumores benignos de ovario, los quistes serosos foliculares fueron los más prevalentes, seguidos de los quistes lúteos. El dolor pélvico fue el síntoma más llamativo. La mayoría de los casos requirieron quistectomía y el 19 % requirió adicionalmente ooforectomía.