Bone Marrow Transplantation Restores Follicular Maturation and Steroid Hormones Production in a Mouse Model for Primary Ovarian Failure

Recent studies suggest that bone marrow stem cells (BMSCs) are promising grafts to treat a variety of diseases, including reproductive dysfunction. Primary ovarian failure is characterized by amenorrhea and infertility in a normal karyotype female, with an elevated serum level of follicle-stimulating hormone (FSH) and a decrease level of estrogen caused by a mutation in FSH receptor (FSHR) gene. Currently, there is no effective treatment for this condition. The phenotype of FSHR (−/−) mouse, FORKO (follitropin receptor knockout), is a suitable model to study ovarian failure in humans. Female FORKO mice have elevated FSH, decreased estrogen levels, are sterile because of the absence of folliculogenesis, and display thin uteri and small nonfunctional ovaries. In this study, we determined the effects of BMSC transplantation on reproductive physiology in this animal model. Twenty four hours post BMSC transplantation, treated animals showed detectable estroidogeneic changes in daily vaginal smear. Significant increase in total body weight and reproductive organs was observed in treated animals. Hemotoxylin and eosin (H&E) evaluation of the ovaries demonstrated significant increase in both the maturation and the total number of the follicles in treated animals. The FSH dropped to 40–50% and estrogen increased 4–5.5 times in the serum of treated animals compared to controls. The FSHR mRNA was detected in the ovaries of treated animals. Our results show that intravenously injected BMSCs were able to reach the ovaries of FORKO mice, differentiate and express FHSR gene, make FSHR responsive to FSH, resume estrogen hormone production, and restore folliculogenesis

Amplified DNA from different tissues of animals transplanted by (+/+) or (−/−) donors.

<p>Amplified DNA from different tissues of animals transplanted by (+/+) or (−/−) donors.</p

Changes of total body weight(A), ovaries(B), uterus(C), vagina and cervix(D), and serum level of FSH(E) and estrogen(F) in treated (Tr) Vs control (Ct) animals at different time points of experiment.

<p>For B, C and D organs weight considered as % of total body weight. Both treated and control group had increase in total body weight but BMT group showed significantly more increase than control group (A, P<0.03). As indicated, reproductive organs which are highly modulated by estrogen, showed remarkable increase in weight at all time points of the experiment except for the first week (for B, C, and D, a P value of less than 0.04 obtained). Bone marrow transplanted animals compare to untreated controls showed 40–50% decrease in serum FSH level (E, P<0.03) and 4–5.5 folds increase in serum estrogen (F, P<0.004) at all time points of experiment.</p

Development of the ovary in BMT animal (A) compared to untreated control animal (B).

<p>Both the total number of follicles and the number of antral follicles are significantly higher in BMT compare to control group. Histological evaluation showed on average 28±4 follicles/ovary in treated group with 8±2 follicles at the antral stage compared to only 6±2 with no follicles at antral stage in untreated control mice. Photos have been taken at the same magnification.</p

Vervet Monkeys Vaccinated with Killed Leishmania major Parasites and Interleukin-12 Develop a Type 1 Immune Response but Are Not Protected against Challenge Infection

Leishmania major is a protozoan parasite that causes chronic cutaneous lesions that often leave disfiguring scars. Infections in mice have demonstrated that leishmanial vaccines that include interleukin-12 (IL-12) as an adjuvant are able to induce protective immunity. In this study, we assessed the safety, immunopotency, and adjuvant potential of two doses of IL-12 when used with a killed L. major vaccine in vervet monkeys. The induction of cell-mediated immunity following vaccination was determined by measuring delayed-type hypersensitivity, in vitro lymphocyte proliferation, and gamma interferon (IFN-γ) production. Protection was assessed by challenging the animals with L. major parasites and monitoring the course of infection. At low doses of IL-12 (10 μg), a small increase in the parameters of cell-mediated immunity was observed, relative to those in animals that received antigen without IL-12. However, none of these animals were protected against a challenge infection. At higher doses of IL-12 (30 μg), a substantial increase in Leishmania-specific immune responses was observed, and monkeys immunized with antigen and IL-12 exhibited an IFN-γ response that was as great as that in animals that had resolved a primary infection and were immune. Nevertheless, despite the presence of correlates of protection, the disease course was only slightly altered, and protection was low compared to that in self-cured monkeys. These data suggest that protection against leishmaniasis may require more than the activation of Leishmania-specific IFN-γ-producing T cells, which has important implications for designing a vaccine against leishmaniasis

Leishmaniose visceral (Calazar): cinco casos em cães de Santa Maria, Rio Grande do Sul, Brasil Visceral Leishmaniasis (kala-azar): five cases in dogs in Santa Maria, Rio Grande do Sul, South Brazil

Leishmaniose visceral foi diagnosticada no exame pós-morte de cinco cães da região de Santa Maria, RS. Todos os animais mostraram sinais de doença crônica com icterícia, anorexia, vômito, febre intermitente e emaciaçâo. Os achados macroscópicos à necropsia foram de gastrenterite hemorrágica, pneumonia intersticial e esplenomegalia. Histologicamente foram detectadas formas livres e intracelulares de Leishmania spp em macrófagos e células endoteliais em todos os tecidos investigados. Estudos epidemiológicos, realizados na região onde a maioria dos casos ocorreu, foram negativos para a detecção do agente e do vetor biológico.<br>Five canine cases of visceral leishmaniasis were diagnosed. All five dogs presented with icterus, intermitent fever, vomition, anorexia and emaciation. The most prominent gross lesions were hemorrhagic gastroenteritis, interstitial pneumonia and splenomegaly. In tissue sections, free and intracellular forms of Leishmania spp were depicted in macrophages and endothelial cells of all organs scanned. Epidemiological survey to detect either the agent or the sandfly was negative