Visfatin protein may be responsible for suppression of proliferation and apoptosis in the infantile mice ovary.

Visfatin is an important adipokines, which are expressed in different tissues including ovary of mammals. The postnatal ovary in rodents undergoes dramatic changes of intra-ovarian factors in relation to proliferation and apoptosis. There are studies which showed that gonadal visfatin changes in postnatal life. However, role of visfatin in the early postnatal period i.e. infantile period has not been studied. Therefore, the present study was aimed to explore the role of visfatin in the early postnatal ovarian functions. Furthermore, to explore the role of visfatin, the endogenous visfatin was inhibited from PND14-PND21 by FK866 with dose of 1.5 mg/kg. Our results showed gain in body weight and ovarian weight after visfatin inhibition. The inhibition of visfatin increased the ovarian proliferation (increase in PCNA, GCNA expression and BrdU incorporation) and apoptosis (increase in BAX and active caspase3 expression). Moreover, visfatin inhibition decreased the expression of antiapoptotic/survival protein, BCL2 in the ovary. These findings suggest that visfatin in the infantile ovary may suppress the proliferation and apoptosis by up-regulating BCL2 expression. An interesting finding has been observed that circulating estrogen and progesterone remain unaffected, although visfatin inhibition up-regulated ER-ß and down-regulated ER-α. It may also be suggested that visfatin could regulates proliferation and apoptosis via modulating estrogen signaling. In conclusion, visfatin inhibits the proliferation and apoptosis without modulating the ovarian steroid biosynthesis and visfatin mediated BCL2 expression could also be mechanism to preserve the good quality follicle in early postnatal period.

The effect of metformin treatment on the basal and gonadotropin-stimulated steroidogenesis in male rats with type 2 diabetes mellitus.

Type 2 diabetes mellitus impairs reproductive functions in men, and important tasks are deciphering the mechanisms of testicular dysfunctions in diabetes and the search of effective approaches to their correction. The purpose was to study the effect of four-week metformin treatment (120 mg kg-1  day-1 ) of male Wistar rats with high-fat diet/low-dose streptozotocin-induced type 2 diabetes on basal and gonadotropin-stimulated steroidogenesis, intratesticular content of leptin and the leptin and luteinising hormone receptors and on spermatogenesis. Diabetic rats had hyperleptinaemia, androgen deficiency and reduced sperm count and quality, and in the testes, they had the increased leptin level and the decreased content of the leptin and luteinising hormone receptors and 17-hydroxyprogesterone. The stimulating effects of chorionic gonadotropin on testosterone production and expression of steroidogenic genes (Star, Cyp11a1) were decreased. Metformin restored basal and gonadotropin-stimulated blood testosterone levels. In the testes, it restored gonadotropin-stimulated 17-hydroxyprogesterone, androstenedione and testosterone levels, Star expression and the content of leptin and the leptin and luteinising hormone receptors. Metformin also improved epididymal sperm count and morphology. We concluded that metformin treatment normalises the testicular steroidogenesis in diabetic rats, which is due to restoration of the gonadotropin and leptin systems in the testes and is associated with an improvement in spermatogenesis.

Dexamethasone mediated downregulation of PGC-1α and visfatin regulates testosterone synthesis and antioxidant system in mouse testis.

Dexamethasone, a synthetic glucocorticoid has been used as an immunosuppressive and anti-inflammatory and affects reproduction. It has been suggested that testicular steroidogenesis involves PGC-1α and visfatin as key regulators. Previous studies have shown that dexamethasone down-regulates PGC-1α and visfatin expression in muscle and mammary epithelial cells respectively. However, the effect of dexamethasone on testicular visfatin and PGC-1α expressions has not been investigated. The aims of the present study were to investigate the effect of dexamethasone, on the expression of PGC-1α, visfatin and antioxidant enzymes activities in mouse testis. The results of the present study showed that dexamethasone treatment significantly decreased the expression of visfatin and PGC-1α in mice testis, along with significant decreased in testicular antioxidant enzymes activates. Further, dexamethasone treatment also significantly increased the testicular lipid peroxidation and decreased testosterone synthesis. The dexamethasone induced changes in PGC-1α and visfatin in the testis were significantly correlated with changes in serum testosterone concentrations and antioxidant enzymes activities. Thus, dexamethasone induced testicular toxicity may involve the PGC-1α and visfatin as important molecules to exhibit its effects.

Alleviating effect of Mallotus roxburghianus in heat-induced testicular dysfunction in Wistar rats.

CONTEXT: Hyperthermia causes detrimental effects on the testes leading to fertility problems. Mallotus roxbhurghianus Muell. Arg. (Euphorbiaceae) is used in traditional medicine and possesses antioxidant property. However, the mechanisms remain unknown in the context of alleviative action of M. roxburghianus against heat stress. OBJECTIVE: The objective of this study was to demonstrate the alleviating activity of M. roxburghianus and its mechanism in scrotal hyperthermia. MATERIALS AND METHODS: Scrotal hyperthermia experiments were performed in three groups (n = 7 per group) consisting of (i) the control group (C) maintained at 22 °C for 30 min, (ii) the heat stress-induced group (HS), and (iii) the heat stress-induced M. roxburghianus-treated group (HSM - 400 mg/kg each) in a thermostatically controlled water bath at 43 °C for 30 min. Subsequent to the heat treatment HS group, rats were treated with saline p.o and methanol extract of M. roxburghianus was administered to the rats of HSM group along with their standard food for 14 d. Scrotal hyperthermic effects were evaluated. RESULTS: Scrotal hyperthermia significantly (p < 0.0001) elevated malondialdehyde levels while decreasing the body and testes weights, serum testosterone, and antioxidant enzyme levels due to oxidative stress. Disorganisation of seminiferous tubules and arrest of spermatogenesis were observed in the HS group. The administration of methanol extract of M. roxburghianus (400 mg/kg) for 14 d after heat treatment significantly suppressed the lipid peroxidation, restored the antioxidant enzyme and testosterone levels, revived the spermatogenesis, and increased the cell proliferation activity in the HSM group. DISCUSSION AND CONCLUSION: The methanol extract of M. roxburghianus accelerates testicular recovery from the damaging influence of hyperthermia.