Abstract
Although melatonin has some of the broadest ranges of actions on the physiology of vertebrates, especially on their reproductive processes, the mechanism by which melatonin regulates animal reproduction is still incompletely understood. This study was designed to determine the effect of oral melatonin on the reproductive performance of female mice. Female ICR mice (7 weeks old) were given melatonin-containing water (3, 30 and 300 μg/mL; melatonin) or water only (control) until 10 weeks of age. Then, some of the mice were successfully mated (confirmed by vaginal plugs), and the number of live births and their weights were recorded. Some mice were used for a histological analysis of the number of follicles in the ovaries. Others were used for oocyte collection after superovulation, and in vitro fertilization (IVF) was performed. The mRNA expression of the apopotosis-related genes (BAX, BCL2) in the IVF embryos were analyzed. After melatonin administration, the mice showed similar serum melatonin levels to that of the control. The number of antral follicles per mm2 unit area in the 30 μg/mL melatonin-treated group (14.60) was significantly higher than that of the control (7.78), which was lower than that of the 3 μg/mL melatonin-treated group (12.29). The litter size was significantly higher in the 3 μg/mL melatonin-treated group (15.5) than in the control (14.3). After IVF, the hatched blastocyst formation rate in the 30 μg/mL melatonin-treated group (85.70%) was significantly higher than that of the control (72.10%), and it was the same for the BCL2/BAX expression ratio. Although oral melatonin did not appear to have an effect on the serum melatonin rhythm in the mouse, melatonin did increase litter size at the 3 μg/mL dose level, and improved the developmental competency of IVF embryos at the 30 μg/mL level.
Highlights
Melatonin (MT, N-acetyl-5 methoxytryptamine), a hormone primarily secreted by the pineal gland, was first isolated and characterized from the bovine pineal gland by Lerner et al in1958 [1]
(0–300 μg/mL) of MT in their drinking water for 3 weeks, the serum MT levels were low in the daytime and high at night, and the circadian rhythms were similar to those of a previous report that serum MT levels were low in the daytime and high at night before and after oral administration of three gelatin capsules, each containing 80 mg crystalline MT at 60 min intervals [22]
The serum MT levels were different between our study and the previous report [22] in the daytime and at night, the peak values were observed at night (314.59–336.63 pg/mL vs. about 100,000 pg/mL)
Summary
Melatonin (MT, N-acetyl-5 methoxytryptamine), a hormone primarily secreted by the pineal gland, was first isolated and characterized from the bovine pineal gland by Lerner et al in1958 [1]. It was found that MT could regulate the seasonal reproduction of mammals through the hypothalamus-pituitary-gonadal axis [2]. Molecules 2018, 23, 1845 hormone (GnRH) pulse generation by the hypothalamus varied [2], which was mainly resulted from changes in the nightly secretion of MT from the pineal gland with the changes of photoperiod, decreasing the negative feedback sensitivity of GnRH neurons to estradiol [3]. Reproductive functions may be regulated by MT via direct action on the gonads. There are two subtypes of receptor, MT receptor 1 (MT1) and MT receptor 2 (MT2), in human luteal granulosa cells [4]. MT could act directly on the target organ (ovary) through its receptors and regulate the synthesis and secretion of gonadal hormones, thereby affecting reproductive functions [5,6]
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