Chemotherapy-induced ovarian damage and protective strategies.

More than 9.2 million women worldwide suffer from cancer, and about 5% of them are at reproductive age. Chemotherapy-induced impairment of fertility affects the quality of life of these women. Several chemotherapeutic agents have been proven to cause apoptosis and autophagy by inducing DNA damage and cellular stress. Injuries to the ovarian stroma and micro-vessel network are also considered as pivotal factors resulting in ovarian dysfunction induced by chemotherapeutic agents. Primordial follicle pool over-activation may also be the mechanism inducing damage to the ovarian reserve. Although many studies have explored the mechanisms involved in chemotherapy-induced reproductive toxicity, the exact molecular mechanisms have not been elucidated. It is essential to understand the mechanisms involved in ovarian damage, in order to develop potential protective treatments to preserve fertility. In this article, we reviewed the current knowledge on the mechanism of chemotherapy-induced ovarian damage and possible protective strategies that prevent the ovary from such damages.

ClpP/ClpX deficiency impairs mitochondrial functions and mTORC1 signaling during spermatogenesis.

Caseinolytic protease proteolytic subunit (ClpP) and caseinolytic protease X (ClpX) are mitochondrial matrix peptidases that activate mitochondrial unfolded protein response to maintain protein homeostasis in the mitochondria. However, the role of ClpP and ClpX in spermatogenesis remains largely unknown. In this study, we demonstrated the importance of ClpP/ClpX for meiosis and spermatogenesis with two conditional knockout (cKO) mouse models. We found that ClpP/ClpX deficiency reduced mitochondrial functions and quantity in spermatocytes, affected energy supply during meiosis and attenuated zygotene-pachytene transformation of the male germ cells. The dysregulated spermatocytes finally underwent apoptosis resulting in decreased testicular size and vacuolar structures within the seminiferous tubules. We found mTORC1 pathway was over-activated after deletion of ClpP/ClpX in spermatocytes. Long-term inhibition of the mTORC1 signaling via rapamycin treatment in vivo partially rescue spermatogenesis. The data reveal the critical roles of ClpP and ClpX in regulating meiosis and spermatogenesis.

Mitochondrial stress response gene Clpp deficiency impairs oocyte competence and deteriorate cyclophosphamide-induced ovarian damage in young mice.

Chemotherapy is extensively used to treat cancers and is often associated with ovarian damage and leads to premature ovarian insufficiency and infertility, while the role of mitochondria during ovarian damage with chemotherapy remains unknown. This study used a mouse model with oocyte-specific deletion of mitochondrial stress response gene Caseinolytic peptidase P (Clpp) to investigate mitochondrial homeostasis in oocytes from mice receiving a chemotherapeutic drug cyclophosphamide (CTX). We found that oocyte-specific deletion of Clpp reduced fecundity of the mice at advanced age. The deletion led to meiotic defects with elevated abnormal spindle rate and aneuploidy rate with impaired mitochondrial function in the MII oocytes from 8-week-old mice. Upon CTX treatment at 8-week-old, the oocyte competence and folliculogenesis from the oocyte-specific Clpp knockout mice was further deteriorated with dramatic impairment of mitochondrial distribution and function including elevated ROS level, decreased mitochondrial membrane potential, respiratory chain activity and ATP production. Taken together, the results indicate that that ClpP was required for oocyte competence during maturation and early folliculogenesis, and its deficiency deteriorate cyclophosphamide-induced ovarian damage.

The interaction between changes in upright mandibular position and supine airway size in patients with obstructive sleep apnea.

INTRODUCTION: The purpose of this study was to investigate the interaction between upright mandibular position change and supine upper airway size in men with obstructive sleep apnea fitted with titratable oral appliances. METHODS: Baseline supine cephalometry before placement of the oral appliance and after titration with the oral appliance in place were undertaken in 14 patients, and upright mandibular position change was evaluated with and without the titrated oral appliance in place with a DigiGraph workstation (Dolphin Imaging Systems, Valencia, Calif). RESULTS: The apnea-hypopnea index was significantly reduced after titration of the oral appliance (P < .01). Upright mandibular position change was associated with significant vertical (P < .01) and horizontal (P < .01) mandibular repositioning. The size of the supine velopharynx (P < .05), but not the supine oropharynx, was significantly enlarged at the titrated mandibular position. The supine oropharyngeal size change was correlated with the upright horizontal repositioning of the mandible (r = 0.69, P < .01). CONCLUSIONS: Evaluation of upright mandibular position changes with the DigiGraph workstation enables one to predict supine oropharyngeal enlargement with oral appliance therapy. Dose-dependent effects of the horizontal component of upright mandibular protrusion on supine oropharyngeal size in addition to velopharyngeal enlargement might contribute to oral appliance effectiveness in obstructive sleep apnea patients.

Effect of impression technique on bond strength.

If the effects of surface preparation (eg, acid etching, laser preparation, crystal growth) are to be investigated on the same tooth from which the bond strength is recorded, a method of surface replication is required that does not affect the subsequent bond. This study investigated the effect of 2 different methods of taking impressions on bond strength. Three groups of 11 mandibular incisors were used. The labial enamel was etched with 37% phosphoric acid for 30 seconds. Group A (control) had no impression taken; in group B (silicone), impressions were taken with silicone impression material before bonding; in group C (polyether), an impression was taken with polyether before bonding. After the impressions were taken, GAC brackets (A Company, San Diego, Calif) were bonded to the labial surfaces of the etched enamel with Transbond XT light-cured composite (3M Unitek, Monrovia, Calif). Teeth with bonded brackets were stored in water at 37 degrees C for 24 hours, and then bond strength was measured on a testing machine. The adhesive remnant index (ARI) was also recorded. The lowest bond strength was found after silicone replication (mean [standard deviation]: 8.6 [1.7] MPa) and the highest in the control group (21.2 [4.0] MPa). There was no significant difference between the control group and the polyether replication group (19.1 [4.7] MPa). The surface detail replications of polyether and silicone were found to be identical. It was concluded that polyether had no significant effect on bond strength and was suitable for surface replication before bonding. Polyether allows replication of the enamel surface without a significant effect on bond strength, and this technique could be used to examine the relationship between enamel preparation techniques and subsequent bond strength between composite and enamel.