Cisplatin and Doxorubicin Induce Distinct Mechanisms of Ovarian Follicle Loss; Imatinib Provides Selective Protection Only against Cisplatin

Chemotherapy treatment in premenopausal women has been linked to ovarian follicle loss and premature ovarian failure; the exact mechanism by which this occurs is uncertain. Here, two commonly used chemotherapeutic agents (cisplatin and doxorubicin) were added to a mouse ovary culture system, to compare the sequence of events that leads to germ cell loss. The ability of imatinib mesylate to protect the ovary against cisplatin or doxorubicin-induced ovarian damage was also examined.Newborn mouse ovaries were cultured for a total of six days, exposed to a chemotherapeutic agent on the second day: this allowed for the examination of the earliest stages of follicle development. Cleaved PARP and TUNEL were used to assess apoptosis following drug treatment. Imatinib was added to cultures with cisplatin and doxorubicin to determine any protective effect.Histological analysis of ovaries treated with cisplatin showed oocyte-specific damage; in comparison doxorubicin preferentially caused damage to the granulosa cells. Cleaved PARP expression significantly increased for cisplatin (16 fold, p<0.001) and doxorubicin (3 fold, p<0.01). TUNEL staining gave little evidence of primordial follicle damage with either drug. Imatinib had a significant protective effect against cisplatin-induced follicle damage (p<0.01) but not against doxorubicin treatment.Cisplatin and doxorubicin both induced ovarian damage, but in a markedly different pattern, with imatinib protecting the ovary against damage by cisplatin but not doxorubicin. Any treatment designed to block the effects of chemotherapeutic agents on the ovary may need to be specific to the drug(s) the patient is exposed to

Effectiveness of GonaCon as an immunocontraceptive in colony-housed cats

Objectives Non-surgical contraceptive management of free-roaming cat populations is a global goal for public health and humane reasons. The objectives of this study were to measure the duration of contraception following a single intramuscular injection of a gonadotropin-releasing hormone-based vaccine (GonaCon) and to confirm its safe use in female cats living in colony conditions. Methods GonaCon (0.5 ml/cat) was administered intramuscularly to 20 intact female cats (queens), and saline was administered to 10 queens serving as sham-treated controls. Beginning in late February, 4 months after injection, all cats were housed with fertile male cats in a simulated colony environment. Time to pregnancy, fetal counts and vaccine-elicited injection-site reactions were evaluated. Results All control cats (n = 10/10) and 60% (n = 12/20) of vaccinated cats became pregnant within 4 months of the introduction of males. Two additional vaccinates became pregnant (70%; n = 14/20) within 1 year of treatment. Average fetal counts were significantly lower in vaccinated cats than in control cats. Vaccinates had a significantly longer (P = 0.0120) median time to conception (212 days) compared with controls (127.5 days). Injection-site reactions ranging from swelling to transient granulomatous masses were observed in 45% (n = 9/20) of vaccinated cats. Conclusions and relevance A single dose of GonaCon provided contraception lasting for a minimum of 1 year in 30% (n = 6/20) of treated cats. The level of contraception induced by this GonaCon dose and vaccine lot was not sufficiently effective to be recommended for use in free-roaming cats

Effectiveness of GonaCon as an immunocontraceptive in colony-housed cats

Objectives Non-surgical contraceptive management of free-roaming cat populations is a global goal for public health and humane reasons. The objectives of this study were to measure the duration of contraception following a single intramuscular injection of a gonadotropin-releasing hormone-based vaccine (GonaCon) and to confirm its safe use in female cats living in colony conditions. Methods GonaCon (0.5 ml/cat) was administered intramuscularly to 20 intact female cats (queens), and saline was administered to 10 queens serving as sham-treated controls. Beginning in late February, 4 months after injection, all cats were housed with fertile male cats in a simulated colony environment. Time to pregnancy, fetal counts and vaccine-elicited injection-site reactions were evaluated. Results All control cats (n = 10/10) and 60% (n = 12/20) of vaccinated cats became pregnant within 4 months of the introduction of males. Two additional vaccinates became pregnant (70%; n = 14/20) within 1 year of treatment. Average fetal counts were significantly lower in vaccinated cats than in control cats. Vaccinates had a significantly longer (P = 0.0120) median time to conception (212 days) compared with controls (127.5 days). Injection-site reactions ranging from swelling to transient granulomatous masses were observed in 45% (n = 9/20) of vaccinated cats. Conclusions and relevance A single dose of GonaCon provided contraception lasting for a minimum of 1 year in 30% (n = 6/20) of treated cats. The level of contraception induced by this GonaCon dose and vaccine lot was not sufficiently effective to be recommended for use in free-roaming cats

Reproductive efficiency of adult and prepubertal goats subjected to repeated follicular aspiration

The objective of this study was to assess the reproductive response of adult and prepubertal goats subjected to repeated laparoscopic ovum pick-up (LOPU). The study animals were divided into two groups, specifically, adult nanny goats (GA, n=10) and prepubertal nanny goats (GP, n=10), which were subjected to estrous synchronization and ovarian stimulation for LOPU. Both groups underwent six LOPU procedures at seven-day intervals and were subsequently subjected to controlled mating and pregnancy diagnosis to evaluate their future fertility. The study showed a reduction in the number of follicles visualized and in the amount and quality of the oocytes that were recovered and exposed to in vitro maturation. As indicated by the fertility test, however, no complications were found during the laparoscopic procedures that would impair the reproductive future of the animals. Therefore, a viable number of oocytes were obtained even with the decreased reproductive efficiency, proving that repeated LOPUs do not interfere with the reproductive of adult and prepubertal nanny goats. These results indicate a positive aspect of this procedure, allowing for increasing reproductive performance of this kind, when used for the production in vitro.O objetivo deste estudo foi avaliar a resposta reprodutiva de cabras adultas e pré-púberes submetidas a repetidas aspirações foliculares por videolaparoscopia (LOPU). Os animais do estudo foram divididos em dois grupos, especificamente cabras adultas (GA, n = 10) e pré-púberes (GP, n = 10), que foram submetidas a sincronização de estro e estimulação ovariana para LOPU. Ambos os grupos foram submetidos a seis procedimentos LOPU em intervalos de sete dias e foram posteriormente submetidos à monta controlada e posterior diagnóstico de gestação para avaliar sua fertilidade. O estudo mostrou uma diminuição do número de folículos visualizados, na quantidade e na qualidade dos oócitos que foram recuperados e expostos à maturação in vitro. Tal como indicado pelo teste de fertilidade, no entanto, não foram observadas grandes complicações durante os procedimentos laparoscópicos que pudessem prejudicar o futuro reprodutivo dos animais. Portanto, foi obtido um número de oócitos viáveis, mesmo com a diminuição da eficiência reprodutiva, provando que repetidas LOPU não interferem na reprodutividade de animais adultos e pré-púberes. Estes resultados indicam um aspecto positivo desse procedimento, possibilitando um aumento da eficiência reprodutiva dessa espécie quando utilizado para a produção in vitro.Universidade Estadual de São Paul

Utilização de estrógeno exógeno no início do ciclo estral em vacas leiteiras mestiças

O objetivo neste trabalho foi verificar o efeito do estrógeno exógeno em fase precoce do ciclo estral na indução do estro e na dinâmica ovariana de vacas leiteiras. Considerando que a PGF2&#945; não regride o corpo lúteo com menos de cinco dias após o estro, uma das alternativas para a redução do intervalo estral no início do ciclo seria o uso do estrógeno. Foram utilizadas 16 vacas mestiças Holandês-Zebu ciclando regularmente, sem qualquer alteração clínica ou reprodutiva. As vacas foram incluídas ao acaso nos respectivos tratamentos. Oito delas receberam 2,5 mL de cipionato de estradiol no primeiro dia do ciclo estral e oito não receberam (controle). A manifestação de estro foi monitorada visualmente. Os exames ultrassonográficos foram realizados diariamente pela manhã, iniciando no dia do estro. As coletas de sangue para as dosagens de progesterona tiveram início no dia do estro. Os animais que receberam estrógeno no primeiro dia após o estro natural manifestaram os sinais característicos de estro (psíquicos, útero túrgido e muco abundante) um dia após a aplicação. Essa redução do intervalo de estro para apenas dois dias pode favorecer a eliminação de bactérias do útero (quando presentes), aumentando a eficiência reprodutiva. Excetuando o dia da emergência da primeira onda folicular, todas as outras variáveis estudadas (número e comprimento de ondas, características dos folículos dominantes e subordinados, assim como os parâmetros relacionados ao corpo lúteo) não foram afetadas pela aplicação de estrógeno um dia após o estro. A aplicação de cipionato de estradiol em vacas mestiças um dia após o estro natural promove o aparecimento de sinais de estro dois dias após o estro natural mas não afeta as características do ciclo estral subsequente.The objective of this work was to check the effect of exogenous estrogen, in early phase of estrus cycle on the induction of estrus and on ovarian dynamics of dairy cows. By considering that PGF2&#945; does not regress the corpus luteum in less than five days after the estrus, an alternative for the reduction of the estrus interval in the beginning of the cycle would be the use of estrogen. It was used 16 Holstein-zebu crossbred cows cycling regularly, without any clinical or reproductive alterations. Cows were randomly included in their respective treatments. Eight cows received 2.5 mL of estradiol cipionate on the first day of the estrous cycle and eight cows did not receive anything (control). The expression of estrus was monitored visually. The ultrasound scans were conducted daily in the morning, starting on the estrus day. The blood collections for the measurements of the levels of progesterone began on the estrus day. All the animals that received estrogen on the first day after natural estrus showed the estrus characteristical signals (psychics, turgid uterus and abundant mucus) one day after application. This reduction of estrus interval to only two days can promote the elimination of uterus bacteria (if present), consequently enhancing the reproductive efficiency. Except for the the day of the first follicular wave emergence, all the other studied variables (wave number and length, characteristics of dominant and subordinate follicles and the parameters related to the corpus luteum) were not affected by the application of estrogen on the day after the estrus. The application of estradiol cipionate in crossbred cows one day after the natural estrus promote the emergence of estrus sign two days after the natural estrus, without affecting the characteristics of the next estrous cycle