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Biomedical subjects

Francesca Maranghi

Publications and source records attributed to Francesca Maranghi.

5 recordsLinked to original sources

Efficient testing strategies for evaluation of xenobiotics with neuroendocrine activity.

Maturation of neuroendocrine regulations is an extremely complex process made up of several stages, that can be permanently affected by any exogenous substances able to interfere with the hormonal signalling at various levels. The Endocrine Disrupting Chemicals (EDCs) are a heterogeneous group of xenobiotics with potential endocrine activities which have been identified as priority risk factors in toxicological research. The present review is aimed at suggesting a number of endocrine and behavioural endpoints to be used in experimental studies to: (i) characterize more thoroughly the functional effects of developmental exposure to agents known to act as endocrine disruptors and (ii) unmask possible interferences with the maturation of the hypothalamus-hypophysis-gonad/thyroid (HHG/Th) axis by different class of xenobiotics not considered as EDCs. A combined testing strategy, considering both markers of endocrine/hormonal maturation and behavioural endpoints under hormonal control in laboratory rodents, may evidence even subtle perturbations of the neuroendocrine homeostasis, that often go undetected.

Animals↗

Risk assessment of chemicals potentially affecting male fertility.

Male reproductive toxicity involves a broad range of targets and mechanisms such as direct effects on the seminiferous epithelium and/or on Leydig and Sertoli cells supporting spermatogenesis, epididymal sperm maturation as well as endocrine disruption. Direct effects on spermatogenesis may be adequately revealed through both reproduction and repeated-dose toxicity studies; however, more research is needed on early markers of effect and on long-term sequelae of short-term exposures. Endocrine-related mechanisms are particularly relevant to subtle, but persistent effects on reproductive development due to altered early programming; the two-generation study is the test of choice, whereas targeted studies on the prepubertal phase are also desirable. Studies using in vitro methods as well as toxicogenomics are increasing; although gaps exist and much validation work is needed, in perspective, such approaches may be important in order to select compound, understand mechanisms, as well identify biomarkers of potential use also in human studies.

Biomarkers↗

Long-term effects of lonidamine on mouse testes.

Lonidamine (LND) [1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid] is a well-known antispermatogenic drug. The aim of this study was to identify its possible long-term sequelae on the reproductive system of mice as compared with rats, where most data have been obtained until now. Sexually mature CD1 male mice were administered a single dose of LND (200 mg/kg bw by gavage) and killed 24 and 48 h, 6 days and 2, 4 and 8 weeks after the treatment. Testes were collected, weighed and (1) fixed in Bouin's solution for histological analysis or (2) reduced to monocellular suspensions and ethanol fixed to undergo flow cytometry (FCM) DNA content analysis. No effect on body weight and/or food consumption was observed in the treated group in comparison with the control group. Testicular weight was significantly reduced 24 h after the treatment. Reduced seminiferous epithelium with a progressive lack of intercellular cohesion and marked depletion of spermatids, infiltration of granulocytes, desquamation into the tubular lumen and increased intertubular spaces were present by 24 h after the treatment and persisted to a marked degree at 48 h, 6 days and 2 and 4 weeks up to a marked degeneration of tubular structures with absence of spermatogenesis. The same effects, albeit with a moderate severity, were still present 8 weeks after the treatment. As also detected by FCM, primary spermatocytes appeared to be the main cellular target. Sertoli and Leydig cells were remarkably spared. The histological findings are consistent with those previously observed in rats and point out that testicular damage may persist for several weeks after a single-dose administration. Findings are discussed in comparison with testicular toxicity elicited by other xenobiotics.

Animals↗

Histological and histomorphometric alterations in thyroid and adrenals of CD rat pups exposed in utero to methyl thiophanate.

Pregnant CD rats were treated with an initial dose of 0, 310 or 560 mg/kg bw per day of the fungicide methyl thiophanate (MT) on gestational days 10-14, corresponding to formation of thyroid and adrenal primordia; newborns were sacrificed on postnatal days (PNDs) 10 and 23. No apparent maternal toxicity and no effects on litter size, viability or weight gain were present. Delayed ear pinna detachment and eye opening were present at top dose level. Thyroid histology showed increased irregular nuclei and/or mitoses (PND 10-both doses), cells with necrotic or hydropic changes (PND 23-top dose). The adrenal cortex showed increased karyomegaly and hydropic degeneration (PND 23-both doses). Thyroid histomorphometry showed reduced follicular density, moderately increased follicular cell height and number of nuclei/follicle (PND 10-top dose and PND 23-both doses), suggesting retarded follicular maturation. The adrenal cortex relative area was slightly decreased (PND 10-top dose and PND 23-both doses).MT may act as weak endocrine disrupter, suggesting that attention should be paid to delayed endocrine alterations elicited by agrochemicals.

Adrenal Glands↗