Up-regulated mRNA expression of VEGFA receptors (FLT1 and KDR) in placentas after assisted reproductive technology fertilization

• Published in: Journal of applied genetics Vol. 65; no. 3; pp. 531 - 540
• Main Authors: Mrozikiewicz, Aleksandra E., Kurzawińska, Grażyna, Walczak, Michał, Skrzypczak-Zielińska, Marzena, Ożarowski, Marcin, Jędrzejczak, Piotr
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-09-2024; Springer Nature B.V
• Subjects: Adult; Angiogenesis; Animal Genetics and Genomics; Biomedical and Life Sciences; Case-Control Studies; Down-regulation; Embryo Transfer; Embryos; Female; Fertilization in Vitro; Fetuses; Fibroblast growth factor 2; Flt1 protein; Gender; Gene expression; Genes; Human Genetics; Human Genetics • Original Paper; Humans; In vitro fertilization; Infant, Newborn; Life Sciences; Male; Microbial Genetics and Genomics; Neonates; Placenta; Placenta - metabolism; Plant Genetics and Genomics; Polymerase chain reaction; Pregnancy; Real time; Receptors; Reproductive Techniques, Assisted; Reproductive technologies; RNA, Messenger - genetics; Statistical analysis; Up-Regulation; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism; Vascular Endothelial Growth Factor Receptor-1 - genetics; Vascular Endothelial Growth Factor Receptor-2 - genetics; Women; ART; FLT1; IVF; Placental expression; KDR; FGF2; VEGFA
• ISSN: 1234-1983; 2190-3883
• DOI: 10.1007/s13353-023-00823-2

Placental angiogenesis is a pivotal process for feto-maternal circulation and ensures efficient development of the placenta throughout pregnancy. Many factors during in vitro fertilization and embryo transfer procedures may affect placental gene expression and fetus development. The present study aimed to identify differences in angiogenesis-related gene (
VEGFA
,
FGF2
,
FLT1
, and
KDR
) expression profiles in placentas after assisted reproductive technology fertilization and natural conception in healthy women. In a case-control study, term placentas were collected from Caucasian women after assisted reproductive technology fertilization (
N
= 20) and after natural conception in women with uncomplicated pregnancy (
N
= 9). The mRNA expression in placentas was examined for
VEGFA
,
FGF2
,
FLT1
, and
KDR
genes by real-time quantitative polymerase chain reaction (RT-qPCR). Group stratification was performed for comparison of investigated genes between the type of embryo transferred (fresh/frozen), place of tissue donation (center/margin), and newborns’ gender (male/female). In the ART placentas, significant down-regulation of
VEGFA
gene (
p
= 0.016) and up-regulation of
FLT1
(
p
= 0.026) and
KDR
(
p
< 0.001) gene receptors were observed. Genes encoding
VEGFA
receptors were up-regulated in both fresh (ET) and frozen (FET) embryo transfer groups compared to controls. For the
FLT1
gene, a statistically significant difference was observed between the frozen embryo transfer group and the controls (
p
= 0.032). Relative expression of
KDR
was significantly higher for both embryo transfer groups compared to controls (
p
< 0.001) and between ET and FET (
p
= 0.002). No statistically significant differences were observed between placental expression in different places of tissue donation and newborns’ gender. We observed differences in the placental expression of
VEGFA
and its receptors
FLT1
and
KDR
in pregnancies after assisted reproductive technology compared to naturally conceived pregnancies. More research is needed to clarify these alterations that may affect placental development and fetal health.