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International Journal of Morphology

On-line version ISSN 0717-9502


AGUIRRE -SAMUDIO, Ana Julia; DE LA FUENTE-JUAREZ, Graciela; MARQUEZ-OROZCO, Amalia  and  MARQUEZ-OROZCO, María Cristina. Histological Changes of the Ovary of Adult Mice Exposed Prenatally to Flunitrazepam . Int. J. Morphol. [online]. 2006, vol.24, n.4, pp.651-658. ISSN 0717-9502.

Flunitrazepam (FNZ) is a minor tranquillizer involving allosteric modulation of the GABA receptor complex. It is a ligand of the peripheral benzodiazepine receptor (PBR) that participates in cholesterol transport in steroidogenic organs. The purpose was to investigate whether a single oral dose of FNZ of 2.5 mg/kg of body weight (bw), administered on day 6 of gestation, alters the structure of the adult ovary of mouse offsprings at 2 months of age. The mouse offsprings of the in utero FNZ-treated group and those of the control group (C) were killed. Ovaries were obtained in early estrous, fixed in Zenker solution, and processed by routine histological techniques. Serial sections were observed under light microscopy to determine the characteristics and quantity of follicles in different stages of development and of the corpus luteum. The ovarian tissues from the FNZ group depicted a great staining affinity, enlarged nuclei with abundant heterochromatin clumps. The quantity of primordial, primary and secondary normal follicles in the FNZ group decreased significantly (p< 0.01). The number of primary atretic follicles increased (p<0.01) and the secondary ones remained constant as in group C. Histological changes and statistical data suggest that FNZ produces long-lasting epigenetic or genotoxic effects in follicular and corpus luteum cells of the ovary of prenatally FNZ-treated mice

Keywords : Benzodiazepine; Flunitrazepam; Atretic follicles; Corpus luteum; Prenatal exposure.

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