The cyclophosphamide is used in cancer treatment. The aim of this study was evaluating the effect of different doses of this drug on male mice reproductive parameters. The cyclophosphamide was administered in the doses 100, 150, 200 e 250 mg.kg -1 , intraperitoneal route, for six weeks. As a result, it was observed a decrease in body mass and a decrease in testicles and kidney's weight, in all animals treated with cyclophosphamide. Only the groups that received the doses 100, 150 mg.kg -1 of cyclophosphamide were able to fertilize their females. There was higher incidence of post-implantation losses, reabsorptions and decrease in fetal viability in the group that received the dose of 150 mg.kg . Based on the methodology used and results obtained, it was concluded that the cyclophosphamide was toxic, considering the decrease in animal's body mass and testicle's weight; promoted hepatotoxicity and nephrotoxic effect; influenced in the animals spermatogenesis taking them to infertility and/or subfertility; decreased fetal viability, despite it didn't cause significant malformations in the offspring.Uniterms: Cyclophosphamide/effects. Cyclophosphamide/toxicity. Spermatogenesis/experimental study. Chemotherapeutics/adverse effects. Fertility/experimental study.A ciclofosfamida é utilizada no tratamento de câncer. Este estudo visa avaliar os efeitos das diferentes doses do fármaco nos parâmetros reprodutivos de camundongos machos. A ciclofosfamida foi administrada nas doses de 100, 150, 200 e 250 mg kg -1 , via intraperitoneal por seis semanas. Como resultado observou-se diminuição de massa corporal, redução no peso de testículos e rins em todos os animais tratados com a ciclofosfamida. Apenas os grupos que receberam as doses de 100 e 150 mg kg -1 do quimioterápico foram capazes de fertilizar as fêmeas. Houve maior incidência de perdas pós-implantação, reabsorção e diminuição da viabilidade fetal no grupo que recebeu a dose de 150 mg kg -1 . Observou-se redução nos pesos dos epidídimos e fígado dos animais tratados com as doses de 150, 200 e 250 mg kg -1 . Espermatozóides anômalos foram encontrados nas doses de 200 e 250mg kg -1 . Com base na metodologia empregada e nos resultados obtidos, conclui-se que a ciclofosfamida foi tóxica considerando-se a redução de massa corporal e o peso dos testículos dos animais; promoveu hepatotoxicidade e efeito nefrotóxico; influenciou na espermatogênese dos animais de forma a levá-los a um estado de infertilidade e/ou subfertilidade; diminuiu viabilidade fetal, entretanto não causou malformações significativas na prole.Unitermos: Ciclofosfamida/efeitos. Ciclofosfamida/toxicidade. Espermatogênese/estudo experimental. Quimioterápicos/efeitos adversos. Fertilidade/ estudo experimental.

Background: Dact gene family encodes multifunctional proteins that are important modulators of Wnt and TGF-b signaling pathways. Given that these pathways coordinate multiple steps of limb development, we investigated the expression pattern of the two chicken Dact genes (Dact1 and Dact2) from early limb bud up to stages when several tissues are differentiating. Results: During early limb development (HH24-HH30) Dact1 and Dact2 were mainly expressed in the cartilaginous rudiments of the appendicular skeleton and perichondrium, presenting expression profiles related, but distinct. At later stages of development (HH31-HH35), the main sites of Dact1 and Dact2 expression were the developing synovial joints. In this context, Dact1 expression was shown to co-localize with regions enriched in the nuclear b-catenin protein, such as developing joint capsule and interzone. In contrast, Dact2 expression was restricted to the interzone surrounding the domains of bmpR-1b expression, a TGF-b receptor with crucial roles during digit morphogenesis. Additional sites of Dact expression were the developing tendons and digit blastemas. Conclusions: Our data indicate that Dact genes are good candidates to modulate and, possibly, integrate Wnt and TGF-b signaling during limb development, bringing new and interesting perspectives about the roles of Dact molecules in limb birth defects and human diseases. Developmental Dynamics 243:428-439, 2014. V C 2013 Wiley Periodicals, Inc.Key words: Dact; Dapper; Frodo; chicken embryo; Wnt; TGF-b; limb; chondrogenesis; appendicular skeleton; Sox9; cartilage; perichondrium; joint; digit blastema; tendon; digit morphogenesis; limb evolution Key findings:Dact1 and Dact2 are dynamically expressed during early chondrogenesis in sites that either overlap or complement Sox9 expression domains. Dact1 and Dact2 are coexpressed in developing joints, tendons, and digit blastemas. Dact1 mRNAs colocalize with nuclear b-catenin protein while Dact2 complements sites of bmpR-1b expression in developing synovial joints of digits.

Regeneration is classically demonstrated in mammals using mice digit tip. In this study, we compared different amputation plans and show that distally amputated digits regrow with morphology close to normal but fail to regrow the fat pad. Proximally amputated digits do not regrow the phalangeal bone, but the remaining structures (nail, skin and connective tissue), all with intrinsic regenerative capacity, re-establishing integrity indistinguishably in distally and proximally amputated digits. Thus, we suggest that the bone growth promoted by signals and progenitor cells not removed by distal amputations is responsible for the re-establishment of a drastically different final morphology after distal or proximal digit tip amputations. Despite challenging the use of mouse digit tip as a model system for limb regeneration in mammals, these findings evidence a main role of bone growth in digit tip regeneration and suggest that mechanisms that promote joint structures formation should be the main goal of regenerative medicine for limb and digit regrowth.

Animal models commonly serve as a bridge between in vitro experiments and clinical applications; however, few physiological processes in adult animals are sufficient to serve as proof-of-concept models for cartilage regeneration. Intriguingly, some rodents, such as young adult mice, undergo physiological connective tissue modifications to birth canal elements such as the pubic symphysis during pregnancy; therefore, we investigated whether the differential expression of cartilage differentiation markers is associated with cartilaginous tissue morphological modifications during these changes. Our results showed that osteochondral progenitor cells expressing Runx2, Sox9, Col2a1 and Dcx at the non-pregnant pubic symphysis proliferated and differentiated throughout pregnancy, giving rise to a complex osteoligamentous junction that attached the interpubic ligament to the pubic bones until labour occurred. After delivery, the recovery of pubic symphysis cartilaginous tissues was improved by the time-dependent expression of these chondrocytic lineage markers at the osteoligamentous junction. This process potentially recapitulates embryologic chondrocytic differentiation to successfully recover hyaline cartilaginous pads at 10 days postpartum. Therefore, we propose that this physiological phenomenon represents a proof-of-concept model for investigating the mechanisms involved in cartilage restoration in adult animals.

RESUMO:A utilização de plantas medicinais sempre foi bem difundida, porém hoje se faz necessária uma abordagem científica para comprovar sua eficácia. Este estudo foi realizado para avaliar a possível toxicidade materna e teratogenicidade do óleo de copaíba, um óleo resina exudado do tronco de Copaifera langsdorfii, muito utilizado na medicina natural. Três doses de óleo de copaíba, administradas por gavage durante 5 dias do período gestacional de fêmeas de camundongos, foram testadas 0,3 mL Kg -1 , 0,6 mL Kg -1 e 0,9 mL Kg -1 (p.c.). Em relação ao ganho de peso materno, peso dos órgãos, número de fetos vivos e implantes e viabilidade fetal, não houve diferença estatística entre os grupos. Os dados demonstram que este fitoterápico não apresenta toxicidade materna. Com relação às médias de peso e comprimento fetal dos grupos tratados, houve diferença estatística quando comparados ao controle, mas os fetos ainda se encontravam dentro do peso adequado à idade de prenhez. A prole das fêmeas tratadas não apresentou malformações ou alterações externas, viscerais e esqueléticas. Os resultados deste estudo indicam que o óleo de copaíba, nas doses administradas e período estudado, não apresentou toxicidade materna ou causou teratogenicidade na prole das fêmeas tratadas. Portanto, podemos considerar seu uso seguro durante o período gestacional. Palavras-chave: Copaifera langsdorfii, plantas medicinais, toxicidade, teratogenicidade, gestaçãoABSTRACT: Copaiba oil (Copaifera langsdorfii Desf.) on mouse reproductive patterns and embryonic or fetal development. The use of medicinal plants has always been widely spread, but today a scientific approach is needed to prove their efficiency. The present study was performed to evaluate the possible maternal toxicity and teratogenicity of copaiba oil, a resin oil exudate from the trunk of Copaifera sp., extensively used in natural medicine. Three copaiba oil levels, administered through gavage for 5 days during the gestational period of female mice, were tested: 0.3 mL Kg -1 , 0.6 mL Kg -1 and 0.9 mL Kg -1 (b.w.). As regards maternal weight gain, organ weight, live fetus number, implants and fetal viability, there was no statistical difference among groups. Data indicate that this phytotherapic drug does not show maternal toxicity. Considering the means of fetal weight and length of treated groups, there was statistical difference when compared with the control group, but the fetuses were still within the appropriate weight to that pregnancy age. The offspring from treated females did not present external, visceral and skeletal alterations or malformations. The results from this study indicate that copaiba oil at the administered levels and studied period did not present maternal toxicity or cause teratogenicity to the offspring of treated females. Therefore, its use can be considered safe during pregnancy. INTRODUÇÃOO uso de plantas medicinais para tratamento, cura e prevenção de doenças tem sido descrito por muitos povos desde os tempos mais remotos. Devido a esse uso, surgiram in...