Effects of lactic acid on expression of placental angiogenesis and fetal growth in mice during early pregnancy

Background Endometrial stromal cells undergo decidualization to further support pregnancy during implantation. Warburg-like glycolysis produces a large amount of lactic acid during decidualization.

Objective To investigate the effects of lactic acid and metabolism on expression of placental angiogenesis and fetal growth in mice during early pregnancy.

Methods CD1 female mice aged 6-8 weeks were selected in this study. Syrosingopine inhibitor (7.5 mg/kg·d) was injected daily intraperitoneally into pregnant mice from 4.5 days of gestation for 3 days (Sy group, n=12). Mice receiving normal saline treatment with an equal injection volume served as control group (NC group, n=12). The gestational sac of mice was weighed at 8.5 days of gestation, and the relative mRNA expression of fetal growth and angiogenesis in decidua tissues of mice was detected by RT-PCR. Fetus and placentas were weighed at 12.5 days of gestation. RT-PCR was used to detect the relative mRNA expression of the placental angiogenesis, and Western blot was used to detect the expression of CD31 protein in placenta.

Results Compared with the NC group, the weight of gestational sac at 8.5 days of gestation decreased significantly in the inhibitor group (P < 0.001). The expression levels of fetal growth and angiogenesis (Opn, Ogn, Angpt2, Angpt4, CD31, Hif-1α, Tgf-1β, Tie-2, Vegfr2 and Vegfr3) in decidua tissues also significantly decreased, and the differences were statistically significant (P < 0.05). The fetus weight (P=0.003), placental weight (P=0.033) and placental efficiency (P < 0.001) at 12.5 days of gestation in mice were decreased in inhibitor group; The mRNA expression levels of Angpt4, CD31, Hif-1α, Tgf-1β, Tie-2, Vegfr2 and Vegfr3 in placental angiogenesis decreased significantly in the inhibitor group (P < 0.05). The expression level of CD31 protein in placental tissue of mice significantly decreased in the inhibitor group (P < 0.05).

Conclusion Inhibition of lactic acid in vivo can reduce the expression of placental angiogenesis and fetal growth in mice during early pregnancy.