Serum deprivation induced in human lymphoblastoid Raji cells oxidative stress-associated apoptotic death and G0/G1 cell cycle arrest. Addition into culture medium of the immunomodulatory protein Seminal vesicle protein 4 (SV-IV) protected these cells against apoptosis but not against cycle arrest. The antiapoptotic activity was related to: (1) decrease of endocellular reactive Oxygen species (ROS) (2) increase of mRNAs encoding anti-oxidant enzymes (catalase, G6PD) and antiapoptotic proteins (survivin, cox-1, Hsp70, c-Fos); (3) decrease of mRNAs encoding proapoptotic proteins (c-myc, Bax, caspase-3, Apaf-1). The biochemical changes underlaying these effects were probably induced by a protein tyrosine kinase (PTK) activity triggered by the binding of SV-IV to its putative plasma membrane receptors. The ineffectiveness of SV-IV to abrogate the cycle arrest was accounted for by its downregulating effects on D1,3/E G1-cyclins and CdK2/4 gene expression, ppRb/pRb ratio, and intracellular ROS concentration. In conclusion, these experiments: (1) prove that SV-IV acts as a cell survival factor; (2) suggest the involvement of a PTK in SV-IV signaling; (3) point to cell cycle-linked enzyme inhibition as responsible for cycle arrest; (4) provide a model to dissect the cycle arrest and apoptosis induced by serum withdrawal; (5) imply a possible role of SV-IV in the survival of hemiallogenic implanting embryos.

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Lizards are soil surface animals that represent an important link between invertebrates and higher predators. Being part of wild fauna, they can be affected by contamination from anthropic activities and in particular, pesticides and chemical substances of various nature that reach the soil surface directly or through fall out. Among these substances, heavy metals such as cadmium may exert particularly marked toxic effect on both adult and embryos. In lizards, recent studies show that cadmium may cause developmental defects, including alteration of eye development, with appearance of unilateral microphthalmia and retinal folding. In the present study, the effects of cadmium incubation on retinal development were investigated demonstrating that cadmium interferes with cell cycle regulation by increasing proliferation. An increased expression of Otx2 and Pax6 genes, markers of retinal differentiation, was also found. However, the cellular localization of Pax6 and Otx2 transcripts did not change in treated embryos: in the early stages of retinogenesis, the two genes were expressed in all retinal cells; in the differentiated retina, Otx2 remained in the cellular bodies of retinal cells forming the nuclear and the ganglion layers, whereas Pax6 was expressed only in the cells of the inner nuclear and the ganglion layers. Data suggest that the increased expression of Pax6 and Otx2 could be ascribed to the hyperproliferation of retinal cells rather than to an effective gene overexpression.

Cadmium is a highly polluting heavy metal known to have undesirable effects on health in both animals and humans, targeting the kidneys, the liver and the vascular system. A wide spectrum of deleterious effects has been reported also on the reproductive organs and the developing embryo. Cadmium in fact is a strong endocrine disruptor that interferes with functioning of endogenous receptors and hormones causing detrimental effects on offspring production and survival. In spite of the wide number of studies carried out in laboratory mammals, data on cadmium effects on gonadic tissues, fertility and reproduction of wild terrestrial vertebrates are still limited. In particular, information on the consequences of environmental cadmium exposure on reptiles survival and biodiversity is particularly scanty. Reptiles are presently considered highly susceptible to a number of environmental pollutants and this has contributed to the global decline of several wild populations of turtles, crocodilians and lizards. In addition, several reptile species have been identified as good bioindicators of pollution in their environments due to their persistence in a variety of habitats, wide geographic distribution, longevity and site fidelity. In consideration of the few data currently available we decided to investigate cadmium effects on oogonial proliferation and oocyte recruitment in a species of lizard and to verify whether this metal acts as an endocrine disruptor. For this purpose, we treated adult females with cadmium or, alternatively, with estradiol, progesterone or follicle stimulating hormone. Results indicate that cadmium stimulates oogonial proliferation and oocyte recruitment by mimicking the effects exerted by gonadotropins. Treatment, in fact, increases preleptotene and zygotene-pachytene oocytes numbers that reach values comparable to those observed after FSH treatment. These values are significantly different, either lower or higher, from those observed after estradiol or progesterone administration. Results also indicate that the supernumerary oocytes produced after cadmium treatment are destined to degenerate and that fecundity is reduced by a significant increase in follicular atresia.

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