Female Reproductive Performance in the Mouse: Effect of Oral Melatonin

Molecules. 2018 Jul 25;23(8):1845. doi: 10.3390/molecules23081845.

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.

Keywords: apopotosis-related genes; follicular density; in vitro development; litter size; mouse; oral melatonin.

MeSH terms

  • Administration, Oral
  • Animals
  • Dose-Response Relationship, Drug
  • Embryonic Development / drug effects*
  • Female
  • Fertilization in Vitro / methods
  • Gene Expression
  • Litter Size
  • Melatonin / administration & dosage
  • Melatonin / metabolism
  • Melatonin / pharmacology*
  • Mice, Inbred ICR
  • Ovarian Follicle / cytology
  • Ovarian Follicle / drug effects
  • Ovary / abnormalities
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Messenger / metabolism
  • Reproduction / drug effects*
  • Superovulation / drug effects
  • Tissue Distribution

Substances

  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Melatonin