Abstract
In mammalian, the periodic growth and development of ovarian follicles constitutes the physiological basis of female estrus and ovulation. Concomitantly, follicular angiogenesis exerts a pivotal role in the growth of ovarian follicles. Melatonin (N-acetyl-5-methoxytryptamine, Mel), exists in follicle fluid, was suggested to affect the development of follicles and angiogenesis. This research was conducted to investigate the effects and mechanisms of Mel on the development of ovarian follicles and its angiogenesis. In total, 40 ICR mice at age of 3 weeks were allocated into four groups at liberty: control, Mel, FSH and FSH + Mel for a 12-day trial. Ovaries were collected at 8:00 a.m. on Day 13 for detecting the development of ovarian follicles and angiogenesis. Results indicated that Mel promoted the development of ovarian follicles of 50–250 μm (secondary follicles) and periphery angiogenesis, while FSH remarkably increased the number of antral follicles and periphery angiogenesis. Mechanically, Mel and FSH may regulate the expression of VEGF and antioxidant enzymes in different follicular stages. In conclusion, Mel primarily acted on the secondary follicles, while FSH mainly promoted the development of antral follicles. They both conduced to related periphery angiogenesis by increasing the expression of VEGF. These findings may provide new targets for the regulating of follicular development.
Highlights
Follicular development is the physiological basis of female estrus and ovulation
The number of follicles of 250–450 μm and >450 μm in the follicle-stimulating hormone (FSH) and follicle stimulating hormone plus melatonin group (FSH+Mel) group increased prominently compared with the control and Mel group (p < 0.01) (Figure 1I), suggesting FSH remarkably increased the number of antral follicles
The expression of CD34 in 50–250 μm follicles in Mel and FSH+Mel group increased very significantly compared with the control group (p < 0.01) and increased significantly compared with FSH group (p < 0.05) (Figure 1D,E), showing Mel was conducive to angiogenesis around secondary follicles
Summary
Follicular development is the physiological basis of female estrus and ovulation. More than 99% of the ovarian follicles undergo atresia during development [1]. Once the follicle begins to enter the developmental stage, its fate cannot be reversed, and either becomes a dominant follicle and releases a mature oocyte, or it moves towards atresia [2]. Growing follicles were classified as primary follicles, secondary follicles, and tertiary follicles. Tertiary follicles include early antral follicles, late antral follicles and preovulatory follicles. The primary and secondary follicles belong to the gonadotropin-independent stage; while in the tertiary follicle, the follicle acquires the sensitivity to gonadotropins, thereby being selected to grow towards the preovulatory follicle, which release oocyte under the stimulation of luteinizing hormone (LH) [3]
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