LH prevents cisplatin-induced apoptosis in oocytes and preserves female fertility in mouse

Premature ovarian failure and female infertility are frequent side effects of anticancer therapies, owing to the extreme sensitivity of the ovarian reserve oocytes to the damaging effects of irradiation and chemotherapy on DNA. We report here a robust protective effect of luteinizing hormone (LH) on the primordial follicle pool of prepubertal ovaries against the cisplatin (Cs)-induced apoptosis. In vitro LH treatment of prepubertal ovarian fragments generated anti-apoptotic signals by a subset of ovarian somatic cells expressing LH receptor (LHR) through cAMP/PKA and Akt pathways. Such signals, reducing the oocyte level of pro-apoptotic TAp63 protein and favoring the repair of the Cs-damaged DNA in the oocytes, prevented their apoptosis. Noteworthy, in vivo administration to prepubertal female mice of a single dose of LH together with Cs inhibited the depletion of the primordial follicle reserve caused by the drug and preserved their fertility in reproductive age, preventing significant alteration in the number of pregnancy and of delivered pups. In conclusion, these findings establish a novel ovoprotective role for LH and further support the very attracting prospective to use physiological 'fertoprotective' approaches for preventing premature infertility and risks linked to precocious menopause in young patients who survived cancer after chemotherapy

Extended 3D approach for quantification of abnormal ascending aortic flow.

BackgroundFlow displacement quantifies eccentric flow, a potential risk factor for aneurysms in the ascending aorta, but only at a single anatomic location. The aim of this study is to extend flow displacement analysis to 3D in patients with aortic and aortic valve pathologies.Methods43 individuals were studied with 4DFlow MRI in 6 groups: healthy, tricuspid aortic valve (TAV) with aortic stenosis (AS) but no dilatation, TAV with dilatation but no AS, and TAV with both AS and dilatation, BAV without AS or dilatation, BAV without AS but with dilation. The protocol was approved by our institutional review board, and informed consent was obtained. Flow displacement was calculated for multiple planes along the ascending aorta, and 2D and 3D analyses were compared.ResultsGood correlation was found between 2D flow displacement and both maximum and average 3D values (r>0.8). Healthy controls had significantly lower flow displacement values with all approaches (p<0.05). The highest flow displacement was seen with stenotic TAV and aortic dilation (0.24±0.02 with maximum flow displacement). The 2D approach underestimated the maximum flow displacement by more than 20% in 13 out of 36 patients (36%).ConclusionsThe extended 3D flow displacement analysis offers a more comprehensive quantitative evaluation of abnormal systolic flow in the ascending aorta than 2D analysis. Differences between patient subgroups are better demonstrated, and maximum flow displacement is more reliably assessed