CHTF18 ensures the quantity and quality of the ovarian reserve†.

The number and quality of oocytes, as well as the decline in both of these parameters with age, determines reproductive potential in women. However, the underlying mechanisms of this diminution are incompletely understood. Previously, we identified novel roles for CHTF18 (Chromosome Transmission Fidelity Factor 18), a component of the conserved Replication Factor C-like complex, in male fertility and gametogenesis. Currently, we reveal crucial roles for CHTF18 in female meiosis and oocyte development. Chtf18-/- female mice are subfertile and have fewer offspring beginning at 6 months of age. Consistent with age-dependent subfertility, Chtf18-/- ovaries contain fewer follicles at all stages of folliculogenesis than wild type ovaries, but the decreases are more significant at 3 and 6 months of age. By 6 months of age, both primordial and growing ovarian follicle pools are markedly reduced to near depletion. Chromosomal synapsis in Chtf18-/- oocytes is complete, but meiotic recombination is impaired resulting in persistent DNA double-strand breaks, fewer crossovers, and early homolog disjunction during meiosis I. Consistent with poor oocyte quality, the majority of Chtf18-/- oocytes fail to progress to metaphase II following meiotic resumption and a significant percentage of those that do progress are aneuploid. Collectively, our findings indicate critical functions for CHTF18 in ensuring both the quantity and quality of the mammalian oocyte pool.

Racial disparities in young women with endometrial cancer.

OBJECTIVE: Although racial disparities in treatment and outcome for endometrial cancer are well recognized, little work has explored disparities in young women. We performed a population-based analysis to compare survival between black and white women with endometrial cancer at <50years of age. METHODS: We used the National Cancer Data Base to identify women <50years of age with endometrial cancer from 1998 to 2012. Clinical and demographic characteristics were compared between black and white women and survival by race analyzed using Kaplan-Meier curves and multivariable Cox proportional hazards models. RESULTS: We identified a total of 35,850 women <50years of age including 31,947 (89.1%) white and 3903 (10.9%) black patients. Black women were more likely to have advanced stage, poorly differentiated, and non-endometrioid histology neoplasms (P<0.05 for all). In a multivariable model, survival was 19% worse for black patients than white patients (HR=1.19; 95% CI, 1.08-1.32). A similar effect was seen when limited to women with early-stage tumors (HR=1.24; 95% CI, 1.04-1.49), while among patients with advanced stage tumors, no association between race and survival was seen (HR=1.12; 95% CI, 0.89-1.41). Five-year survival rates were 90.6% (95% CI, 88.6-92.3%) for white and 81.5% (95% CI, 73.0-87.5%) for black women with stage IB tumors, and 75.1% (95% CI, 72.5-77.5%) and 63.3% (95% CI, 54.1-71.2%) for white and black women with stage III tumors, respectively. CONCLUSIONS: Young black women are more likely to present with pathologically aggressive, advanced stage tumors. Even after adjusting for these pathologic differences, young black women with endometrial cancer have higher mortality than white women.

Adolescent Female With Turner's Syndrome and 46,X,der(Y) del(Y)(p11.2)del(q11.2) Karyotype With Gonadoblastoma and Dysgerminoma.

Gonadal dysgenesis patients with Y chromosomal material are subject to increased risk for germ cell tumors. We report a case of an adolescent female presenting with Turner-like syndrome with primary amenorrhea and Tanner stage 1 breast development. Karyotype showed one X chromosome and a minute pericentromeric fragment of Y chromosome without any functional Y genes in all the cells, unlike a mosaic pattern, represented as 46,X,der(Y)del(Y)(p11.2)del(q11.2). Laparoscopic bilateral gonadectomy was performed due to presence of Y chromosome material and histopathology confirmed gonadoblastoma with a focus of dysgerminoma of the right ovary. A robotic-assisted surgical staging for dysgerminoma was performed which was confirmed to be negative for malignancy. This points at the putative genes for gonadoblastoma to be present around the centromere of the Y chromosome.