Effects of Melatonin on Early Pregnancy in Mouse: Involving the Regulation of StAR, Cyp11a1, and Ihh Expression

Int J Mol Sci. 2017 Jul 27;18(8):1637. doi: 10.3390/ijms18081637.


To test whether melatonin plays an important role in the process of early pregnancy, melatonin was given in drinking water to pregnant mice at different gestation stages. These included mice who were given melatonin 14 days prior to their successful mating (confirmed by vaginal plug) (Group A), after successful mating (Group B), and 14 days prior to and until after successful mating (Group C). Melatonin administration significantly enhanced serum as well as ovarian melatonin levels in the mice. It was observed that melatonin did not affect the natural estrous of mice. On day 0.5 of gestation (D0.5), melatonin not only elevated progesterone (P) secretion, but also upregulated expressions of StAR and Cyp11a1, the two marker genes of corpus luteum in ovaries (p < 0.05). Group A had a significantly lower estradiol (E₂) secretion and a higher number of implantation sites as well as litter size than controls (p < 0.05) and also had an increased Ihh expression in endometrium of D7.5 gestation. Melatonin treatment after successful mating improved the progesterone (P) secretion at D7.5 of gestation (p < 0.05) and significantly induced leukaemia inhibitory factor (LIF) expression (p < 0.05). Our study indicates that melatonin treatment up-regulated the genes involved in pregnenolone synthesis in ovary and Ihh expression in uterine endometrium. The mechanisms of melatonin to improve embryo implantation related to their actions on promoting the development of corpus luteum before gestation and helping to specify uterine receptivity in early pregnant mice.

Keywords: E2; P; corpus luteum; early pregnancy; melatonin; mice.

MeSH terms

  • Animals
  • Animals, Newborn
  • Cholesterol Side-Chain Cleavage Enzyme / metabolism*
  • Embryo Implantation / drug effects
  • Endometrium / drug effects
  • Endometrium / metabolism
  • Estradiol / blood
  • Estrous Cycle / drug effects
  • Female
  • Gene Expression Regulation, Developmental / drug effects
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism*
  • Leukemia Inhibitory Factor / genetics
  • Leukemia Inhibitory Factor / metabolism
  • Litter Size
  • Melatonin / pharmacology*
  • Mice
  • Ovary / drug effects
  • Ovary / metabolism
  • Phosphoproteins / metabolism*
  • Pregnancy
  • Progesterone / blood
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism


  • Hedgehog Proteins
  • Leukemia Inhibitory Factor
  • Phosphoproteins
  • RNA, Messenger
  • ihh protein, mouse
  • steroidogenic acute regulatory protein
  • Progesterone
  • Estradiol
  • Cholesterol Side-Chain Cleavage Enzyme
  • Melatonin