Vascular endothelial growth factor induces anti‑Müllerian hormone receptor 2 overexpression in ovarian granulosa cells of in vitro fertilization/intracytoplasmic sperm injection patients.
Misregulation of vascular endothelial growth factor A (VEGF‑A) has been implicated in numerous types of ovarian disease, such as polycystic ovarian syndrome, ovarian hyperstimulation syndrome, endometriosis and ovarian cancer. VEGF regulates blood vessel permeability and angiogenesis. In our previous study, VEGF‑regulated gene expression was profiled in the uterus of a transgenic mouse model with repressed VEGF expression, which indicated that VEGF is an important regulator in controlling gene expression in the uterus. The anti‑Müllerian hormone (AMH) is expressed by ovarian granulosa cells (GCs) and acts through its type 2 receptor, AMH receptor 2 (AMHR2). Serum AMH levels are used to predict ovarian reserves and the small antral follicles contribute markedly to the serum AMH level. AMH recruits primordial follicles and inhibits excessive follicular development by follicular stimulating hormone (FSH). However, AMH may be influenced by suppression of gonadotrophin secretion and VEGF inhibition. In the current study, human primary ovarian GCs were isolated from ovarian follicle fluid of in vitro fertilization/intracytoplasmic sperm injection cycles (IVF/ICSI). It was identified that the FSH receptor was consistently expressed in the isolated cells. VEGF‑A treatment stimulated AMHR2 overexpression at the gene and protein levels. In addition, VEGF induced AMHR2 expression on the surface of the isolated GCs from mature follicles. The VEGF treatment was also performed in an ovarian granulosa‑like cell line, KGN. AMH and AMHR2 are co‑expressed in normal GCs; however, as a result of VEGF misregulation, AMHR2 overexpression increases AMH binding, which may attenuate follicular or oocyte maturation. However, the associated function and underlying mechanism requires further investigation.
Reproductive Medical Center, Jilin Province People's Hospital, Changchun, Jilin 130021, P.R. China.
Yanqiu
Y
Fang
Reproductive Medical Center, Jilin Province People's Hospital, Changchun, Jilin 130021, P.R. China.
Xiaodan
X
Lu
Reproductive Medical Center, Jilin Province People's Hospital, Changchun, Jilin 130021, P.R. China.
Lei
L
Liu
Reproductive Medical Center, Jilin Province People's Hospital, Changchun, Jilin 130021, P.R. China.
Xiuying
X
Lin
Reproductive Medical Center, Jilin Province People's Hospital, Changchun, Jilin 130021, P.R. China.
Munan
M
Sun
Reproductive Medical Center, Jilin Province People's Hospital, Changchun, Jilin 130021, P.R. China.
Jianhua
J
Fu
Reproductive Medical Center, Jilin Province People's Hospital, Changchun, Jilin 130021, P.R. China.
Shufen
S
Xu
Reproductive Medical Center, Jilin Province People's Hospital, Changchun, Jilin 130021, P.R. China.
Yan
Y
Tan
D000328:Adult; D000818:Animals; D002460:Cell Line; D005260:Female; D005786:Gene Expression Regulation; D006107:Granulosa Cells / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D018000:Receptors, Peptide / Q000096:biosynthesis*; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis*; D020554:Sperm Injections, Intracytoplasmic; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000494:pharmacology*
D018000:Receptors, Peptide; D018125:Receptors, Transforming Growth Factor beta; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C084621:anti-Mullerian hormone receptor