Human oocytes harboring damaged DNA can complete meiosis I.

OBJECTIVE: To determine whether human oocytes possess a checkpoint to prevent completion of meiosis I when DNA is damaged. DESIGN: DNA damage is considered a major threat to the establishment of healthy eggs and embryos. Recent studies found that mouse oocytes with damaged DNA can resume meiosis and undergo germinal vesicle breakdown (GVBD), but then arrest in metaphase of meiosis I in a process involving spindle assembly checkpoint (SAC) signaling. Such a mechanism could help prevent the generation of metaphase II (MII) eggs with damaged DNA. Here, we compared the impact of DNA-damaging agents with nondamaged control samples in mouse and human oocytes. SETTING: University-affiliated clinic and research center. PATIENT(S): Patients undergoing ICSI cycles donated GV-stage oocytes after informed consent; 149 human oocytes were collected over 2 years (from 50 patients aged 27-44 years). INTERVENTIONS(S): Mice and human oocytes were treated with DNA-damaging drugs. MAIN OUTCOME MEASURE(S): Oocytes were monitored to evaluate GVBD and polar body extrusion (PBE), in addition to DNA damage assessment with the use of γH2AX antibodies and confocal microscopy. RESULT(S): Whereas DNA damage in mouse oocytes delays or prevents oocyte maturation, most human oocytes harboring experimentally induced DNA damage progress through meiosis I and subsequently form an MII egg, revealing the absence of a DNA damage-induced SAC response. Analysis of the resulting MII eggs revealed damaged DNA and chaotic spindle apparatus, despite the oocyte appearing morphologically normal. CONCLUSION(S): Our data indicate that experimentally induced DNA damage does not prevent PBE in human oocytes and can persist in morphologically normal looking MII eggs.

Amount of Progesterone Consumed Based on Varying Fat Concentrations, Dietary Recommendations, and Estimated Safe Levels in Commercial Cow Origin Liquid Dairy Products.

Federal guidelines recommend that food with hormone content fall below 1% of endogenous production in the subset of the population with the lowest daily production. The majority of dairy products are obtained from pregnant cows, which increase the level of hormones present. The purpose of this article was to perform theoretical evaluation of the quantity of progesterone in cow's milk based on fat percentages and to assess whether this was within the recommended range. Daily recommended dairy product intake from various countries worldwide was researched. This was compared to the concentration of progesterone previously identified in varying fat contents of cow origin milk to assess the amount of progesterone (mg/day) that would be consumed if the guidelines were followed. The maximum daily progesterone consumption suggested will be met by ingestion of 2.7 L, 1.42 L, 1.13 L, 940 mL, 810 mL, 650 mL of 0% (skim), 1%, 2%, 3.25%, 10% (cream), and 35% (whipping cream) fat liquid cow origin dairy product, respectively. Therefore, ingestion of the highest amount of recommended daily dairy intake fell below 1% of the daily endogenous quantity produced, except in the unlikely case of consumption of 650 mL of 35% fat. Studies demonstrating an effect of cow's liquid dairy product intake may need to be revisited, since levels of progesterone consumption remain within the recommended levels. However, it should be considered that ingestion of cow's milk might have a potential effect on the hormonal profile in patients; however, this seems unlikely.