Sat. Jan 22nd, 2022

Placenta - the smoking gun for cardiovascular disease

The collective activity of massive genes, known as polygenic activity, is involved in the development of hypertension. Some genes are expressed in the kidneys and adrenal glands to regulate blood pressure, but most are related to the development and function of the vascular system. The expression and function of these genes vary from person to person due to differences in the nucleotide sequence (single nucleotide polymorphisms (SNPs) marked with stars) that may be associated with disease. The sum of these differences is assessed by the polygenic risk score (PRS). This represents a person’s genetic risk of developing hypertension during their lifetime. Although maternal hypertension PRS is inversely correlated with offspring birth weight, the actual blood pressure in pregnant women did not have such a relationship with birth weight. Hypertension develops at an older age in women. This study revealed that it is not the blood pressure but the placenta, a vascular organ that mediates the relationship between maternal hypertension PRS and birth weight. A higher genetic risk of hypertension in the mother results in decreased growth of the placenta, which in turn inhibits fetal growth. Credit: Department of Molecular Epidemiology, TMDU

Cardiovascular disease is the leading cause of death worldwide. Although the development of these disorders is most often associated with lifestyle factors such as obesity, increasing evidence suggests that events much earlier in one’s life may also play a role. In a recent article published in BMC Medicine, a team led by researchers at Tokyo Medical and Dental University (TMDU) investigated how low birth weight and fetal growth restriction may be due to the mother having certain variants of hypertension-related genes. Interestingly, these consequences can occur despite the mother not having high blood pressure during pregnancy.

Genetic factors from the mother can affect her child through the direct transmission of certain alleles, but they can also do so indirectly via the intrauterine environment. Studies examining such phenomena have recently suggested that women with genes related to hypertension risk are more likely to give birth to children with low birth weight. Researchers and clinicians therefore assumed that mothers with higher systolic blood pressure would have lower-weight newborns. However, no such correlation was observed. This led the TMDU group to believe that the intrauterine environment plays more of a role in this case. They assumed that all these observations were caused by effects on the placenta.

“We focused on the placenta because it is an extremely vascular organ. Placental weight is also often associated with birth weight,” says Noriko Sato, associate professor at the Department of Molecular Epidemiology, who led the study. “Genome-wide association studies have shown that many blood pressure-related genes are involved in vascular system development and function.”

The researchers studied fetal growth in a cohort of Japanese individuals. They used a person’s genetic risk to develop hypertension during life, called a polygenic risk score, to investigate how the mother’s genetic score affected placental weight and birth weight. Thereafter, the mediating role of the placenta in terms of influence on birth weight was formally verified by the method, called a causal mediation analysis.

“We also focused on genetic variants of vascular-related blood pressure genes to see if the impact on birth weight could ultimately be through influencing placental growth,” explains senior author Naoyuki Miyasaka, professor of Comprehensive Reproductive Medicine. “Almost 100% of the effect of ‘vasculature-related’ genetic scores on birth weight was actually mediated by placental weight.”

The team also found an inverse relationship between the mother’s genetic risk score for systolic blood pressure and the rate of fetal growth towards the end of pregnancy, specifically around 36 weeks of pregnancy.

“Our results suggest that maternal blood pressure-related genes are associated with unwanted fetal growth deceleration by affecting placental growth,” Sato explains. “The intrauterine environment constructed by the placental vasculature is the primarily relevant factor here rather than the mother’s blood pressure at the time of pregnancy.”

This study provides strong evidence that maternal genes associated with hypertension risk can indirectly affect fetal growth and cause long-term effects on a baby via effects on the placenta. Fetal growth restriction at the end of pregnancy occurs in more than a few percent of pregnancies, and it is mostly of unknown cause and difficult to predict. However, the incorporation of genetic risk information for the mother into clinical practice may allow for screening and improved perinatal treatment for mother-child health. Furthermore, the results contribute to the development of new therapeutic targets for the treatment and prevention of hypertension and cardiovascular disease. These results are fascinating because they provide data that can help prevent the development of disease decades before potential onset.

Researchers associate higher maternal blood pressure with changes in the placenta

More information:
Noriko Sato et al., Placenta mediates the effect of maternal hypertension polygenic score on offspring birth weight: a study of birth cohorts with fetal growth rate data, BMC Medicine (2021). DOI: 10.1186 / s12916-021-02131-0

Provided by Tokyo Medical and Dental University

Citation: Placenta: The smoking gun for cardiovascular disease (2021, December 3) retrieved December 3, 2021 from

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