Fetal exposure of Aristolochic Acid I undermines ovarian reserve by disturbing primordial folliculogenesis.

The primordial follicle pool established in early life determines the ovarian reserve in the female reproductive lifespan. Premature exhaustion of primordial follicles contributes to primary ovarian insufficiency (POI), that is dependent by the initial size of the primordial follicle pool and by the rate of its activation and depletion. AAI, a powerful nephrotoxin with carcinogenic potential, is present in the Aristolochiaceae species, which can release AAI into soil as a persistent pollutant. In order to assess the potential risk of Aristolochic Acid I (AAI) exposure on mammalian oogenesis, we uncovered its adverse effect on primordial folliculogenesis in the neonatal mouse ovary and its effect on female fertility in adulthood. Pregnant mice were orally administrated with doses of AAI without hepatic or renal toxicity during late-gestation. Ovaries from offspring of administered female displayed gross aberrations during primordial folliculogenesis. Also, unenclosed oocytes in germ-cell cysts showed increased DNA damage. Furthermore, several key factors, including NANOS3, SOX9, KLF4, that govern early gonad's differentiation were abnormally expressed in the exposed ovary, while the follicle formation was partially restored by knockdown of Nanos3 or sox9. In adulthood, these aberrations evolved into a significant reduction in offspring number and impaired ovarian reserve. Together, our results show that AAI influences primordial folliculogenesis and, importantly, affected female fertility. This study shows that administration of drugs herbs or consumption of vegetables that contain AAs during pregnancy may adversely influence the fertility of offspring.

Autophagy participates in cyst breakdown and primordial folliculogenesis by reducing reactive oxygen species levels in perinatal mouse ovaries.

The reserve of primordial follicles, which serves all oocytes for the female reproductive lifespan, is established a few days after birth in mice. During this process, more than half of the oocytes are primarily eliminated by apoptosis. Autophagy, the conserved intracellular process maintaining cellular homeostasis, serves as a protective mechanism for oocyte survival. In the current study, we speculate a new role for autophagy during primordial folliculogenesis. Active autophagy was observed in perinatal ovaries from 16.5 days post coitus to 3 days post parturition. The inhibition of autophagy by 3-methyladenine (3-MA) increased the number of cyst oocytes and delayed follicle formation in vivo and in organ cultures. Furthermore, the reactive oxygen species (ROS) level was elevated in ovaries treated with 3-MA, while N-acetylcysteine, an oxidant, alleviated the inhibitory effect of 3-MA on primordial folliculogenesis. Additionally, the expression of growth differentiation factor 9 and transforming growth factor ß1, which regulates follicle activation, was decreased after 3-MA treatment. These data suggest that the physiological level of autophagy in perinatal ovaries regulates germ cell cyst breakdown and primordial follicle assembly by ROS clearance and exerts extensive effects on further follicular development.

Application of light microscopy tissue slices and digital slicing in experimental teaching of micromorphology / 中华医学教育探索杂志

Histology teaching requires a combination of theory and experiment for a better understanding of microstructure and related functions of body.On the basis of the comparison and summary of the advantages and limitations of traditional light microscopy tissue slices and the emerging digital slicing,we combined them in the teaching of micromorphology experiments to achieve a better teaching results.Each experimental course (about 3 to 4 hours) was divided into four parts:teaching videos,observation of light microscopy tissue slices and digital slicing,discussion on course content and random quizzes.This teaching method contributed to the improvement of the students' interest and motivation in learning,the teachers' teaching efficiency and the overall teaching quality.

Practice of discussion teaching mode in histology and embryology teaching and its reflection / 中华医学教育探索杂志

Discussion teaching mode was carried out in the teaching of histology and embryol-ogy for clinical medical undergraduates in Chongqing Medical University from aspects of proposing questions, group learning, class discussing and summarizing. Classroom tests were accompanied to evaluate the teaching effect. It showed the discussion teaching achieved satisfactory effects. The correct answer rate of 92.36%students was≥60%. Students not only acquired knowledge but also increased their comprehensive abilities. The well-supervised topics, active participation of students and timely summary of teachers at the end of the class were the key factors in the practice of the discussion teaching mode.