Transforming Growth Factor (TGF) β and Endometrial Vascular Maturation

Abstract

Appropriate growth and development of the endometrium across the menstrual cycle is key for a woman’s quality of life and reproductive well-being. Recurrent pregnancy loss (RPL) and heavy menstrual bleeding (HMB) affect a significant proportion of the female population worldwide. These endometrial pathologies have a significant impact on a woman’s quality of life as well as placing a high economic burden on a country’s health service. An underlying cause for both conditions is unknown in approximately 50% of cases. Previous research has demonstrated that aberrant endometrial vascular maturation is associated with both RPL and HMB, where it is increased in RPL but reduced in HMB. TGFβ1 is one of the key growth factors that regulate vascular maturation, by inducing phenotypic switching of vascular smooth muscle cells (VSMCs) from a synthetic phenotype to a more contractile one. Our previous data demonstrated an increase in TGFβ1 in the endometrium of RPL, while others have shown a decrease in women with HMB. However, TGFβ1 bioavailability is tightly controlled, and we therefore sought to perform an extensive immunohistochemical analysis of different components in the pathway in the endometrium of normal controls, women with HMB or RPL. In addition, two in vitro models were used to examine the role of TGFβ1 in endometrial vascular maturation and endothelial cell (EC):VSMC association. Taken all together, the immunohistochemical data suggest a decrease in bioavailability, receptor binding capacity, and signaling in the endometrium of women with HMB compared with controls. In contrast, there is an increase in the bioavailability of active TGFβ1 in the endometrium of women with RPL compared with controls. Endometrial explants cultured in TGFβ1 had an increase in the number of vessels associated with contractile VSMC markers, although the total number of vessels did not increase. In addition, TGFβ1 increased EC:VSMC association in an in vitro model. In conclusion, TGFβ1 is a key regulator of endometrial vascular maturation and could be considered as a therapeutic target for women suffering from HMB and/or RPL.

TGFβ1 as a Predictive Biomarker for Collateral Formation Within Ischemic Moyamoya Disease

“…The TGFβ1 was observed to be overexpressed in the MCA of MMD, and the TGFβ1 is secreted as a multifunctional polypeptide growth factor in the plasma ( 16 , 17 ). ELISA was performed to detect the concentration of TGFβ1 in plasma.…”

“…Transforming growth factor-beta 1 (TGFβ1) is secreted as a latent form and functions as a multifunctional polypeptide growth factor acting as a significant modulator of cellular growth and differentiation, also playing a vital role in regulating the expression of potent angiogenic factors ( 16 , 17 ). There is a high level of TGFβ1 in the serum of patients with MMD that has been shown in previous research ( 17 – 19 ).…”

Expression deregulation of matrix metalloproteinases and vasoconstriction related genes in Pakistani females with abnormal uterine bleeding

“…Moreover, females of different age groups had shown reduced levels of TGFB3 compared to healthy female group. Reported data has suggested the possible association of aberrant vascular maturity to heavy menstrual bleeding (HMB) and recurrent pregnancy loss [44]. Reduced expression of TGFβ1 was observed in women with heavy menstrual bleeding [50].…”

“…TGFB playing its role in tumor progression by stimulating tumor growth and metabolism and is one of the key element involved in pathology of uterine fibroid [17]. Low expression and down signaling of TGFB1 was observed in endometrium of female diagnosed with heavy menstrual bleeding [44]. TGFB involved in vascular growth directly by interacting with extra cellular matrix (ECM).…”

The Menstrual Endometrium: From Physiology to Future Treatments

“…The decreased bioavailability of HIF1A and TGFB in patients with AUB-E may affect vascular repair and/or angiogenesis after endometrial shedding ( 65 ). Defects in spiral arteriole maturation have been described in AUB.…”