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Premature ovarian failure (POF) is a complicated disorder related to the apoptosis of granulosa cells. The incidence of chemotherapy-associated POF is rising dramatically owing to the increasing proportion of cancer in adolescents. According to previous studies, oxidative stress caused by chemotherapeutic agents plays an important role in the development of POF. However, the exact effects of nuclear factor-erythroid 2-related factor2 (NRF2), a pivotal anti-oxidative factor, are still unknown in chemotherapy-associated POF. Firstly, we manipulated NRF2 expressions on a genetic or pharmaceutical level in cisplatin-injured granulosa cell models. The results indicate that the increasing NRF2 in cisplatin-injured cells was just compensatory and not enough to resist the accumulated stress. Upregulation of NRF2 could protect granulosa cells against cisplatin via elevating autophagic level by using an autophagic activator (rapamycin) and inhibitor (chloroquine). Additionally, exogenous FGF2 exerted a protective role by increasing NRF2 expression and promoting its nuclear translocation. Meanwhile, the results in cisplatin-POF mice models were consistent with what was found in injured cells. In conclusion, our research proved that FGF2 rescued cisplatin-injured granulosa cells through the NRF2-autophagy pathway and might provide a possible alternative treatment choice by targeting NRF2 for POF patients who are intolerant or unsuitable to FGF2. [ABSTRACT FROM AUTHOR]

We recently mapped Idd4 to a 5.2 cM interval on chromosome 11 with two subloci, Idd4.1 and Idd4.2, in nonobese diabetic (NOD) mice. Based on the localization of platelet-activating factor acetylhydrolase Ib1 ( PAF-AHIb1) and the decreased activity of PAF-AH in type 1 diabetes (T1D) patients, we hypothesized that PAF-AHIb1 in Idd4.1 is a candidate gene. The PAF-AHIb1 gene in NOD mice was cloned and sequenced, and its expression and function were studied. No polymorphisms were detected in PAF-AHIb1 cDNA between NOD and B6 mice. The expression of PAF-AH Ib1 at the mRNA and protein levels was found to be similar in different tissues between NOD and B6 mice. PAF-AH activity does not differ in the pancreatic islets or spleen between NOD and B6 mice. Our findings suggest that PAF-AH Ib1 may not be a diabetes-susceptibility gene in the Idd4.1 sublocus. [ABSTRACT FROM AUTHOR]