There has been an increase in reports of male reproductive disorders that include male infertility and testicular cancer worldwide. It has been suggested that agents such as xenoestrogens could be responsible. Xenoestrogens are chemical compounds that mimic the action of estrogens by binding to the estrogen receptors (ERs). The response ofa testicular cell line to estrogenic pesticides was examined. The effect of estrogenic pesticides on the growth and protein levels of ERα and ERβ of mouse Sertoli cells was investigated. Pyrethroids are widely used insecticides due to their insecticidal potency and low mammalian toxicity. In this study, the estrogenicity ofpyrethroid chemicals were tested using the yeast estrogen screen (YES) assay. The toxic effects of the pyrethroid compounds cypermethrin, 3-(4-hydroxy-phenoxy)benzyl alcohol (metabolite of permethrin), and the commercial product (Ripcord Plus) were evaluated. The Sertoli cells were exposed to pyrethroids at concentrations of 0.36 nM and 36 µM (cypermethrin and Ripcord Plus), and 0.69 nM and 69 µM (metabolite) for 100 h. The expression of the ERs was analysed through the use of Enzyme Linked ImmunoSorbent Assay (ELISA) experiments. The most toxic pyrethroid was the metabolite, followed by Ripcord Plus then cypermethrin. Overall the exposure of the cells to cypermethrin (36 µM), Ripcord Plus (36 µM) and the metabolite (69 µM) caused a significant decrease (p<0.05) in ERα levels. In the cultures exposed to the metabolite (69 µM), there was also a significant increase in ERβ levels. There appears to be a relation between cell toxicity and an increase in ERβ levels, which supports the theory that ERβ promotes apoptosis. Pyrethroids are rapidly excreted from the body, and it is unknown if there is accumulation in the male testes. Male fertility could be affected through molecular mechanisms involving the ERs, should cells in the male testes be exposed to these pyrethroids at physiologically relevant concentrations.

There has been an increase in reports of male reproductive disorders that include male infertility and testicular cancer worldwide. It has been suggested that agents such as xenoestrogens could be responsible. Xenoestrogens are chemical compounds that mimic the action of estrogens by binding to the estrogen receptors (ERs). The response ofa testicular cell line to estrogenic pesticides was examined. The effect of estrogenic pesticides on the growth and protein levels of ERα and ERβ of mouse Sertoli cells was investigated. Pyrethroids are widely used insecticides due to their insecticidal potency and low mammalian toxicity. In this study, the estrogenicity ofpyrethroid chemicals were tested using the yeast estrogen screen (YES) assay. The toxic effects of the pyrethroid compounds cypermethrin, 3-(4-hydroxy-phenoxy)benzyl alcohol (metabolite of permethrin), and the commercial product (Ripcord Plus) were evaluated. The Sertoli cells were exposed to pyrethroids at concentrations of 0.36 nM and 36 µM (cypermethrin and Ripcord Plus), and 0.69 nM and 69 µM (metabolite) for 100 h. The expression of the ERs was analysed through the use of Enzyme Linked ImmunoSorbent Assay (ELISA) experiments. The most toxic pyrethroid was the metabolite, followed by Ripcord Plus then cypermethrin. Overall the exposure of the cells to cypermethrin (36 µM), Ripcord Plus (36 µM) and the metabolite (69 µM) caused a significant decrease (p<0.05) in ERα levels. In the cultures exposed to the metabolite (69 µM), there was also a significant increase in ERβ levels. There appears to be a relation between cell toxicity and an increase in ERβ levels, which supports the theory that ERβ promotes apoptosis. Pyrethroids are rapidly excreted from the body, and it is unknown if there is accumulation in the male testes. Male fertility could be affected through molecular mechanisms involving the ERs, should cells in the male testes be exposed to these pyrethroids at physiologically relevant concentrations.

The commonest reproductive disorders of young men (namely low sperm counts, testicular germ cell cancer) may originate in fetal life similar to established disorders (cryptorchidism, hypospadias) that manifest at birth. These disorders are interlinked and may comprise a testicular dysgenesis syndrome (TDS), a concept supported by animal model studies. The latter have identified the likely time-frame within which TDS disorders may be induced, namely within the so-called masculinisation programming window (MPW). During this critical period, sufficient testosterone (androgen) must be produced by the fetal testis to program the male reproductive tract so that it will differentiate and grow normally after the MPW. Impaired androgen production or action within the MPW can result in smaller reproductive organs and their abnormal formation and function (e.g. cryptorchidism, hypospadias). The MPW is thus of fundamental importance in determining normal, or abnormal, male reproductive development and function for later life. There are two big unanswered questions about the MPW. First, what determines its timing? Second, what mechanisms are controlled by androgens specifically within this time-window and not at later time points? Three approaches were undertaken to address the first question experimentally in rats. First, investigation of whether the availability of androgens and or androgen receptors (AR) plays a role in determining the onset or ‘opening’ of the MPW. Second, investigation of whether the expression of AR co-regulators was a factor in determining androgen sensitivity during the MPW. Third, investigation of whether prostaglandins played a role in mediating androgen action in the MPW, as studies in the 1980s had suggested this possibility. To address what mechanisms are controlled by androgens specifically within the MPW, the expression of selected genes in the genital tubercle was investigated before, during and after the MPW in fetuses that had been exposed to treatments that modulated androgen action. Selection of genes was based on microarray studies and data reported in the literature (ie candidate genes). The studies reported in this thesis show that neither availability of androgens nor the AR are important in determining onset of the MPW, and providing exogenous androgens either prior to or during the MPW does not advance or enhance masculinisation. These studies also showed that females may have a slightly different window of susceptibility to androgen action than do males. Key AR co-regulators have been characterized in the male reproductive tract for the first time, two of which (BRG1, CBP) show changes in expression through development of the testis consistent with a role in Sertoli cells. Another AR co-regulator, RWDD1, was found to switch off in the absence of androgen action in the genital tubercle, pointing to a potential role during and/or after the MPW. Studies involving gestational exposure to indomethacin (a compound which inhibits prostaglandin synthesis) during the MPW showed no detectable effect on masculinisation. Finally, evaluation of candidate genes for mediating androgen action in the genital tubercle during the MPW, failed to identify their key involvement, thus they are unlikely to be involved in penis development and disorders such as hypospadias.

<p>Neospora caninum је интрацелуларна парaзитска кокцидија, која припада колу<br />Apicomplexa, фамилији Sarcocystidae, a oдгoвoрна je зa aбoртусe код крава ширoм свeтa.<br />Зоонотски карактер ове протозое за сада није доказан. Ипак, имунокомпромитованим особама<br />препоручује се избегавање контакта са познатим изворима N. caninum<br />Један од проблема у говедарству, су велики економски губици због неоспорозе у<br />стадима високо продуктивних плоткиња услед абортуса. Проценат абортуса се креће oд 0,4-<br />10,6% мада ове вредности могу бити и знатно више ако су инфективни агенси присутни у<br />стадима. Пошто болест пролази у већини случајева без клиничких симптома, абортуси у првој<br />трећини гравидитета могу бити непримећени тако да је губитке врло често тешко и<br />документовати.<br />Плод код заражене јединке може бити ресорбован код раног гравидитета, аутолизован<br />или мумифициран у каснијем стадијуму гравидитета или пак мртворођен. Међутим,<br />забележени су и случајеви живо рођених телади са клиничким симптомима болести или рођени<br />без клиничких симптома али позитивном серолошком реакцијом. Поред високе стопе абортуса<br />на фармама код животиња оболелих од неоспорозе који представљају директну штету,<br />економски губици се огледају и у смањеној концепцији. Нису занемарљиви ни индиректни<br />трошкови везани за ветеринарске услуге у првом реду у успостављању дијагнозе која је тешка<br />и скупа. Вишекратним вештачким осемењавањем се повећава индекс осемењавања, а због<br />смањене концепције продужава се и сервис период, смањује производња млека. Заражена стада<br />прати повећан број превремених тељења, као и рађање авиталне телади те смањени прираст<br />јунади у тову . Годишње серолошко тестирање би могло бити од користи за стратегију<br />контроле серопозитивности на N. caninum.<br />Циљ овог истраживања био је да се утврди серопреваленца Neospora caninum код крава<br />на територији Војводине. Истаживање је обухватило 376 млечних крава, старости преко 24<br />месеца, различитих раса, подељених у три групе:<br />прву групу обухватале су краве са репродуктивним поремећајима,<br />другу групу чиниле су краве без репродуктивних поремећаја,<br />трећу групу краве чија је репродуктивна историја непозната.<br />На основу добијених резултата може се закључити да је неоспооза код крава доказана<br />на целој територији АП Војводине. Укупна преваленца износи 15,4%. Код крава са побачајима<br />и другим репродуктивним поремећајима серопреваленца износи 12,8%, а код крава без<br />репродуктивних поремећаја она износи 18,8%. У раду није доказана статистички значајна<br />разлика у серопреваленци између крава са и без репродуктивних поремећаја.<br />Серопреваленца на малим приватним газдинствима износи 20,2% и статистички је<br />значајно већа у односу на велике комерцијалне фарме где износи 6,2%.<br />Из добијених резултата може се закључити да је једини доказани фактор ризика за<br />појаву неоспорозе код говеда у Војводини узгој на малим приватним газдинствима, што се<br />може објаснити слабом применом зоохигијенских мера, односно слободним држањем и<br />присуством паса на фарми.</p> / <p>Neospora caninum je intracelularna parazitska kokcidija, koja pripada kolu<br />Apicomplexa, familiji Sarcocystidae, a odgovorna je za abortuse kod krava širom sveta.<br />Zoonotski karakter ove protozoe za sada nije dokazan. Ipak, imunokompromitovanim osobama<br />preporučuje se izbegavanje kontakta sa poznatim izvorima N. caninum<br />Jedan od problema u govedarstvu, su veliki ekonomski gubici zbog neosporoze u<br />stadima visoko produktivnih plotkinja usled abortusa. Procenat abortusa se kreće od 0,4-<br />10,6% mada ove vrednosti mogu biti i znatno više ako su infektivni agensi prisutni u<br />stadima. Pošto bolest prolazi u većini slučajeva bez kliničkih simptoma, abortusi u prvoj<br />trećini graviditeta mogu biti neprimećeni tako da je gubitke vrlo često teško i<br />dokumentovati.<br />Plod kod zaražene jedinke može biti resorbovan kod ranog graviditeta, autolizovan<br />ili mumificiran u kasnijem stadijumu graviditeta ili pak mrtvorođen. Međutim,<br />zabeleženi su i slučajevi živo rođenih teladi sa kliničkim simptomima bolesti ili rođeni<br />bez kliničkih simptoma ali pozitivnom serološkom reakcijom. Pored visoke stope abortusa<br />na farmama kod životinja obolelih od neosporoze koji predstavljaju direktnu štetu,<br />ekonomski gubici se ogledaju i u smanjenoj koncepciji. Nisu zanemarljivi ni indirektni<br />troškovi vezani za veterinarske usluge u prvom redu u uspostavljanju dijagnoze koja je teška<br />i skupa. Višekratnim veštačkim osemenjavanjem se povećava indeks osemenjavanja, a zbog<br />smanjene koncepcije produžava se i servis period, smanjuje proizvodnja mleka. Zaražena stada<br />prati povećan broj prevremenih teljenja, kao i rađanje avitalne teladi te smanjeni prirast<br />junadi u tovu . Godišnje serološko testiranje bi moglo biti od koristi za strategiju<br />kontrole seropozitivnosti na N. caninum.<br />Cilj ovog istraživanja bio je da se utvrdi seroprevalenca Neospora caninum kod krava<br />na teritoriji Vojvodine. Istaživanje je obuhvatilo 376 mlečnih krava, starosti preko 24<br />meseca, različitih rasa, podeljenih u tri grupe:<br />prvu grupu obuhvatale su krave sa reproduktivnim poremećajima,<br />drugu grupu činile su krave bez reproduktivnih poremećaja,<br />treću grupu krave čija je reproduktivna istorija nepoznata.<br />Na osnovu dobijenih rezultata može se zaključiti da je neospooza kod krava dokazana<br />na celoj teritoriji AP Vojvodine. Ukupna prevalenca iznosi 15,4%. Kod krava sa pobačajima<br />i drugim reproduktivnim poremećajima seroprevalenca iznosi 12,8%, a kod krava bez<br />reproduktivnih poremećaja ona iznosi 18,8%. U radu nije dokazana statistički značajna<br />razlika u seroprevalenci između krava sa i bez reproduktivnih poremećaja.<br />Seroprevalenca na malim privatnim gazdinstvima iznosi 20,2% i statistički je<br />značajno veća u odnosu na velike komercijalne farme gde iznosi 6,2%.<br />Iz dobijenih rezultata može se zaključiti da je jedini dokazani faktor rizika za<br />pojavu neosporoze kod goveda u Vojvodini uzgoj na malim privatnim gazdinstvima, što se<br />može objasniti slabom primenom zoohigijenskih mera, odnosno slobodnim držanjem i<br />prisustvom pasa na farmi.</p> / <p>Sarcocystidae, responsible for abortion in cattle worldwide. Although zoonotic nature<br />of this protozoa has not been proven, it is generally recommended that immunocompromised<br />persons should avoid contact with the known sources of N. caninum.<br />One of the problems that affect cattle breeding industry are great economic losses due<br />to neosporosis-related abortions in herds of highly productive cows. The percentage of<br />abortions ranges from 0.4% to 10.6%, although it may reach considerably higher values when<br />the infectious agent is present in flocks. Since the disease is asymptomatic in the majority of<br />cases, abortions in the first trimester of pregnancy may remain undetected so that the losses<br />are often difficult to document.<br />Depending on the gestational age of the calf, the outcome of infection may vary from<br />the foetal resorption in early pregnancies, autolysis and mummification in the later course of<br />the gestation, or the occurrence of stillbirths. However, cases of birth of both clinically<br />diseased and asymptomatic, but seropositive newborns, from the infected mothers, have been<br />recorded. In addition to the direct damage reflected in the high rate of abortions, affected<br />farms also suffer significant economic losses due to decreased conception rates in infected<br />cows. Also, indirect costs of veterinary services, especially those regarding expensive and<br />toilsome diagnostic procedures, are not negligible. Finally, repeated artificial insemination<br />increases insemination index and decreased conception rate results in prolonged service<br />period and reduced milk production. Infected herd exhibits increased number of early calving<br />as well as birth of non-vital calves and reduced growth in beef cattle. Serological testing,<br />conducted on yearly basis, could contribute to the development of a control strategy of<br />seropositivity of the cattle to N. caninum.<br />Aim of this research was to determine seroprevalence of N. caninum in cows from the<br />territory of Vojvodina. The study included 376 dairy cows over 24 months of age, of different<br />breeds and divided into three groups, according to their medical history:<br /> The first group consisted of cows with reproductive disorders<br /> The second group consisted of cows without evident reproductive disorders<br /> The third group consisted of cows with unknown medical history<br />Based on these results it can be concluded that neosporosis in cows was demonstrated<br />throughout the territory of the Vojvodina province, with overall prevalence of 15.4%. In cows<br />with abortions and other reproductive disorders seroprevalence was 12.8% and in cows<br />without reproductive disorders it was 18.8%. No statistically significant difference in<br />seroprevalences between cows with and without reproductive disorders was observed.<br />In small private holdings, seroprevalence reached 20.2% which was significantly<br />higher compared to the 6.2% detected on large commercial farms.<br />According to these results, the only proved risk factor for acquisition of neosporosis<br />in cattle in Vojvodina is cattle being bred on private smallholdings, which could probably be<br />explained by poor zoohygienic measures, free-range to semi-confined production systems<br />and the presence of dogs, all of which are often associated with this type of farms.</p>

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniversitet, 2008. / Härtill 6 uppsatser.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniv., 2002. / Härtill 4 uppsatser.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniv., 2002. / Härtill 5 uppsatser.

Thesis (M.Sc.) Uppsala : Sveriges lantbruksuniversitet.

Made available in DSpace on 2014-10-09T12:52:55Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T13:58:46Z (GMT). No. of bitstreams: 0 / Dissertacao (Mestrado) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

Made available in DSpace on 2014-10-09T12:52:55Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T13:58:46Z (GMT). No. of bitstreams: 0 / Apesar dos inúmeros grupos de pesquisa de todo o mundo investigando o câncer, esta doença tem se ampliado significativamente. No caso do câncer de ovário, a despeito dos notáveis avanços observados nos tratamentos atuais, um desafio persiste: a incapacidade da preservação de oócitos em tratamento com quimioterapia, radioterapia e/ou cirurgia, nos quais são freqüentes os efeitos colaterais tais como a perda folicular, a infertilidade, a menopausa precoce e as falências ovarianas pós-quimioterapia, decorrentes da irradiação e pós-cirurgia. Neste sentido, o transplante de tecido ovariano pode representar uma alternativa na recuperação da capacidade fértil da mulher, bem como uma terapia de reposição hormonal após tratamento. No presente estudo, foram utilizadas linhagens de camundongos para avaliar a viabilidade do transplante ovariano antes e após a irradiação, como alternativa para a restauração das funções reprodutivas. Para tanto, fêmeas das linhagens isogênicas C57BL/6/Unib e híbridas B6CF1/Unib, foram acasaladas com machos da linhagem C57BL/6/Unib, empregandose diferentes protocolos com fêmeas submetidas ou não aos efeitos da radiação gama de Co-60 nas doses de 4 Gy e 6 Gy. Os resultados demonstram que a transferência ovariana restabeleceu a capacidade reprodutiva dos animais para níveis muito próximos dos normais; que o tamanho médio da ninhada, não revelou diferenças significativas após a transferência ovariana; que os fragmentos do ovário da receptora permanecem funcionais em períodos próximos pós à irradiação com 4 Gy e 6 Gy e que a irradiação nas doses de 4 Gy e 6 Gy destroem as células germinativas comprometendo a reprodução. / Dissertacao (Mestrado) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP