Estrogen 17β‑estradiol accelerates the proliferation of uterine junctional zone smooth muscle cells via the let‑7a/Lin28B axis in adenomyosis

Abstract

The estrogen 17β-estradiol has been proven to serve an indispensable role in the occurrence and development of adenomyosis (ADS). The let-7a/Lin28B axis can control cell proliferation by acting as a tumor-inhibiting axis in numerous types of cancer. However, its role in ADS remains unknown. The present study aimed i) to elucidate the role of let-7a in regulating the proliferation of human uterine junctional zone (JZ) smooth muscle cells (SMCs) in ADS, ii) to evaluate whether 17β-estradiol modifies the expression levels of let-7a and Lin28B in JZ SMCs in ADS, and iii) to establish how 17β-estradiol affects the function of the let-7a/Lin28B axis in the proliferation of JZ SMCs in ADS. A total of 36 premenopausal women with ADS were enrolled as the experimental group and 34 women without ADS were recruited as the control group. Reverse transcription-quantitative PCR was used to evaluate the expression level of let-7a, and western blotting was performed to determine the Lin28B expression levels. Lentiviral null vector, let-7a overexpression lentiviral vector GV280 and let-7a inhibition lentiviral vector GV369 were used to infect cells to alter the expression of let-7a for further functional experiments. 17β-estradiol and Cell Counting Kit-8 assays were conducted to determine how 17β-estradiol affects the function of the let-7a/Lin28B axis in the proliferation of JZ SMCs in ADS. The results demonstrated that let-7a was downregulated and Lin28B was upregulated in the JZ SMCs of ADS compared with the control cells (P<0.0001). Moreover, a lower expression of let-7a led to faster proliferation of JZ SMCs (P<0.05), and 17β-estradiol affected the let-7a/Lin28B axis to accelerate the proliferation of JZ SMCs in ADS (P<0.05). These data suggested that 17β-estradiol collaborates with the let-7a/Lin28B axis to affect the development of ADS.

Light‐initiated chemiluminescent assay of 17β‐estradiol metrological traceability system established by manufacturer according to ISO17511:2020 and basic performance evaluation performed by clinical end‐users

“…In addition, decreased blood E 2 concentration can also lead to bone loss, uterine atrophy, and aging. 8 , 9 , 10 , 11 Therefore, the ability to accurately measure E 2 levels is of much clinical significance. Moreover, improving the detection sensitivity of E 2 at low levels is important for the diagnosis and monitoring of various diseases characterized by decreased E 2 levels.…”

“…Similarly, pathological decrease in E 2 caused by dysfunction of the hypothalamic‐pituitary‐ovarian axis and other nonspecific reasons often leads to disorders such as female sexual infantile syndrome, delayed puberty, and secondary amenorrhea. In addition, decreased blood E 2 concentration can also lead to bone loss, uterine atrophy, and aging 8‐11 …”

Menstrual cycle and gynecologic pathology in menstrual-related migraine

“…1) в группе МАМ в сравнении с НММ, при отсутствии достоверных отличий в отношении аномальной длительности менструации, достоверно чаще отмечается длительность menses >6 дней; 2) при МАМ пациентки чаще отмечают более обильные менструации, имеется тенденция к наличию тяжелых менструальных кровотечений, ограничивающих социальную и физическую активность; 3) за исключением аменореи, у пациенток, страдающих МАМ, чаще регистрируются аномальные по длительности и регулярности менструальные циклы; 4) при МАМ чаще встречается ежемесячная боль внизу живота во время менструации, требующая применения обезболивающих препаратов (дисменорея). Перечисленные особенности менструальной функции у женщин с МАМ (а именно: увеличение длительности и обильности менструации, дисменорея) могут указывать на проявление системной или локальной гиперэстрогении [19][20][21][22]. В свою очередь, для патогенеза МАМ полученные данные могут иметь особое значение: более высокий системный/локальный уровень эстрогена, возможно, обусловливает более выраженное перименструальное его снижение и, таким образом, увеличивает риск провокации приступа ММ [15].…”

Lin28B overexpression decreases let-7b and let-7g levels and increases proliferation and estrogen secretion in Dolang sheep ovarian granulosa cells

“…Mammalian follicle development is a key process within the ovary, to which GCs directly contribute through their proliferation and growth (Lv et al, 2019). In this context, previous reports indicate interactions among E2, Lin28B, and the let-7 family; 17-β-estradiol and let-7a-Lin28B axes synergistically affect the occurrence and development of adenomyosis (Huang et al, 2021). Additionally, treating MCF-7 cells with 17-β-estradiol (E2) resulted in rapid and specifically reduced let-7g expression (Qian et al, 2011).…”