A Case of Ovarian Dysplasia and a Vaginal Fibroleiomyoma in a Young Golden Retriever

This case demonstrates a unique ovarian congenital anomaly that likely contributed to the development of a rare fibroleiomyoma in the cranial vagina of a young bitch. A 13 month old intact female Golden Retriever presented to the veterinary teaching hospital for urinary incontinence, hematuria, and persistent vaginal discharge. Physical examination revealed a mucopurulent serosanguinous malodorous vulvar discharge, and after further diagnostics was reclassified as persistent estrus. Abdominal palpation and ultrasound revealed uterine thickening and poorly visualized ovaries. The reproductive tract was removed during an ovariohysterectomy, revealing small ovaries and a white anterior vaginal mass. Histopathology revealed dysplastic ovaries with hyperplastic granulosa cells and a benign vaginal fibroleiomyoma. These morphologic changes are consistent with elevated estrogen levels. It was thus concluded that her persistent estrus and the fibroleiomyoma were both secondary to persistent estrogen production by the hyperplastic granulosa cells.

IGF-1 Inhibits Apoptosis of Porcine Primary Granulosa Cell by Targeting Degradation of BimEL

Insulin-like growth factor-1 (IGF-1) is an intra-ovarian growth factor that plays important endocrine or paracrine roles during ovarian development. IGF-1 affects ovarian function and female fertility through reducing apoptosis of granulosa cells, yet the underlying mechanism remains poorly characterized. Here, we aimed to address these knowledge gaps using porcine primary granulosa cells and examining the anti-apoptotic mechanisms of IGF-1. IGF-1 prevented the granulosa cell from apoptosis, as shown by TUNEL and Annexin V/PI detection, and gained the anti-apoptotic index, the ratio of Bcl-2/Bax. This process was partly mediated by reducing the pro-apoptotic BimEL (Bcl-2 Interacting Mediator of Cell Death-Extra Long) protein level. Western blotting showed that IGF-1 promoted BimEL phosphorylation through activating p-ERK1/2, and that the proteasome system was responsible for degradation of phosphorylated BimEL. Meanwhile, IGF-1 enhanced the Beclin1 level and the rate of LC3 II/LC3 I, indicating that autophagy was induced by IGF-1. By blocking the proteolysis processes of both proteasome and autophagy flux with MG132 and chloroquine, respectively, the BimEL did not reduce and the phosphorylated BimEL protein accumulated, thereby indicating that both proteasome and autophagy pathways were involved in the degradation of BimEL stimulated by IGF-1. In conclusion, IGF-1 inhibited porcine primary granulosa cell apoptosis via degradation of pro-apoptotic BimEL. This study is critical for us to further understand the mechanisms of follicular survival and atresia regulated by IGF-1. Moreover, it provides a direction for the treatment of infertility caused by ovarian dysplasia, such as polycystic ovary syndrome and the improvement of assisted reproductive technology.

Is There a Relationship between Ovarian Epithelial Dysplasia and Infertility?

Aim.Ovarian epithelial dysplasia was initially described in material from prophylactic oophorectomies performed in patients at genetic risk of ovarian cancer. Similar histopathological abnormalities have been revealed after ovulation stimulation. Since infertility is also a risk factor for ovarian neoplasia, the aim of this study was to study the relationship between infertility and ovarian dysplasia.Methods.We blindly reviewed 127 histopathological slides of adnexectomies or ovarian cystectomies according to three groups—an exposed group to ovulation induction (n= 30), an infertile group without stimulation (n= 35), and a spontaneously fertile control group (n= 62)—in order to design an eleven histopathological criteria scoring system.Results.The ovarian dysplasia score was significantly higher in exposed group whereas dysplasia score was low in infertile and control groups (resp., 8.21 in exposed group, 3.69 for infertile patients, and 3.62 for the controls). In the subgroup with refractory infertility there was a trend towards a more severe dysplasia score (8.53 in ovulation induction group and 5.1 in infertile group).Conclusion.These results raise questions as to the responsibility of drugs used to induce ovulation and/or infertility itself in the genesis of ovarian epithelial dysplasia.

Ovarian Epithelial Dysplasia and Prophylactic Oophorectomy for Genetic Risk

Objective:To make an accurate histopathological description of ovarian dysplasia in a population at genetic risk of ovarian cancer and devise an ovarian dysplasia score.Materials and Methods:In this retrospective cohort study, 90 patients who had undergone bilateral oophorectomy or ovarian cystectomy between 1992 and 2005 and whose ovaries were reported as normal were divided into two groups: Group A comprising prophylactic oophorectomies for genetic predisposition (N = 28), and Group B or control group, fertile and non-cancerous (N = 62). Eleven epithelial cytological and architectural features were defined. Ovaries were analysed and reviewed by four pathologists blinded to clinical data. An ovarian dysplasia score was devised to quantify extent of ovarian epithelial abnormalities. The degrees of ovarian epithelial abnormalities (dysplasia scores) were compared between the two groups.Results:Mean dysplasia score was significantly higher in Group A (prophylactic oophorectomies) than in Group B (control group) (9.67 vs. 4.19, P < 0.001). In Group A, we observed a gradation in the severity of the dysplastic lesions between (i) proven BRCA mutations and prophylactic oophorectomies without mutations (11.26 vs. 8.1), and (ii) according to age (10.27 after age 50 years vs. 8.6 before age 50 years, P = 0.2962).Conclusion:These results suggest abnormalities in ovaries from high risk women. The ovarian dysplasia may be a pre-malignant, non-invasive histological lesion that could be an important step in early neoplasia.