Exogenous melatonin ameliorates embryo-maternal cross-talk in early pregnancy in sheep.

Abstract

Early pregnancy losses cause 25% of pregnancy failures in small ruminants because of an asynchrony between conceptus and uterine signals. In that context, melatonin plays a crucial role in sheep reproductive dynamics, but little is known about its effects in the peri-implantation period. We hypothesized that melatonin supports embryo implantation by modulating the uterine microenvironment. This study aimed to assess the effects of exogenous melatonin on the endometrium and early placenta rearrangement. Ten multiparous ewes either did (MEL, n=5) or did not (CTR, n=5) receive a subcutaneous melatonin implant (18 mg) 50 d before a synchronized mating. On Day 21 of pregnancy, sheep were euthanized. MEL ewes exhibited a higher prolificity rate (2.8 vs. 2.0 embryos/ewe) and plasma progesterone levels (3.84 vs. 2.96 ng/mL, P<0.05) than did CTR ewes. Groups did not differ significantly in embryo crown-rump length. MEL placenta had significantly (P<0.001) more binucleated trophoblast cells in the chorion region and ovine placental lactogen expression was significantly (P<0.05) more strongly upregulated than it was in CTR. Exogenous melatonin increased significantly (P<0.05) gene expression of angiogenic factors (VEGFA, VEGFR1, IGF1R), IFNAR2, and PR in the caruncular endometrium. Expression of the MT2 receptor in the endometrium and placenta was significantly (P<0.05) higher in MEL group. Results indicate that melatonin implants acted differentially on the uterus and placenta rearrangement. Melatonin increases differentiation in the placenta and induces changes that could promote vessel maturation in the endometrium, which suggests that it enhances the uterine microenvironment in the early stage of pregnancy in sheep.