Cisplatin- and cyclophosphamide-induced primordial follicle depletion is caused by direct damage to oocytes.

It is well established that DNA-damaging chemotherapies can cause infertility and ovarian endocrine failure by depleting the ovarian reserve of primordial follicles. Currently, no effective pharmacological therapies exist for the preservation of long-term fertility and ovarian function in female cancer patients, due to a limited understanding of the mechanisms of chemotherapy-induced follicle depletion. This study investigated the cellular targets, molecular mechanisms, and temporal course of ovarian reserve depletion following treatment with commonly used chemotherapeutic drugs. Adult female C57BL/6 mice were injected i.p. with saline, cisplatin (5mg/kg), or cyclophosphamide (300mg/kg); ovaries were harvested after 8 or 24 hours. Follicle counts showed depletion of all follicular stages 24 hours after administration of cisplatin or cyclophosphamide. Eight hours post-treatment, H2A histone family member X (γH2AX) immunofluorescence showed DNA double-stranded breaks at all follicular stages, including within primordial follicle oocytes. This staining was resolving by 24 hours, indicating that primordial follicle oocytes begin to undergo either apoptosis or repair in this timeframe. γH2AX-positive follicles were further examined to identify the specific cell types damaged. In primordial, transitional, and primary follicles, only oocytes sustained DNA damage, whereas in secondary and antral follicles, only somatic cells were affected. TUNEL staining confirmed that apoptosis occurs in these targeted cell types. Whilst multi-drug and multi-dose regimens were not examined, this study conclusively shows that cyclophosphamide and cisplatin cause direct damage to primordial follicle oocytes, which then undergo apoptosis. Therefore, future pharmacological strategies to prevent chemotherapy-induced infertility in females must specifically prevent primordial follicle oocyte death.

A rare case of a scuba diver's death due to propeller injuries of a desalination pump.

Water skiing, boat racing, skin and scuba diving, as well as pleasure boat cruising are becoming increasingly popular hobbies. As a result, the incidence of injuries secondary to motor propellers is becoming more frequent. Injuries by propellers, amputation, death by drowning, and bleeding are rare reported events in forensic literature. The most common circumstances surrounding boat-propeller-related injuries are concerned with getting into or out of the boat, personal watercraft use or water skiing, and falling or being thrown from the boat. A case of a scuba diver's death that occurred during an illegal scuba fishing trip around a desalination plant is presented. A complete autopsy and histological study of all organs and surfaces of dismembered cadaveric sections, performed in order to determine the phases of death, are reported. An underwater scene investigation was conducted by an engineering team studying the mouth of the pump and the dynamic characteristic of rotating propeller blades.