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Uterine leiomyomas (ULMs) are benign oestrogen-dependent tumours of the myometrium. They are the most common tumours of the female genital tract, affecting around 77% of the female population. ULMs are more common in Black women than White women. These tumours tend to develop earlier and be more numerous, larger in size and more symptomatic in Black women than other ethnic groups. The molecular mechanism underlying this ethnic disparity is not fully understood. Polymorphism of genes involved in oestrogen synthesis and/or metabolism (COMT, CYP17), variation in the expression levels or function of oestrogen and progesterone receptors or retinoic acid nuclear receptors (retinoid acid receptor-α, retinoid X receptor-α), or aberrant expression of micro-RNAs are some of the molecular mechanisms that may be involved. Keywords molecular genetics; race; leiomyomaUterine leiomyomas (ULMs) are benign, monoclonal tumours of the smooth muscle cells of the myometrium. They are composed of large amounts of extracellular matrix containing collagen, fibronectin and proteoglycan. 1 ULMs may cause significant morbidity through their presence in the uterus and pelvic cavity. These benign tumours are a significant cause of pelvic pain, abnormal uterine bleeding, infertility and pregnancy complications. 2 ULMs are the most common tumours of the female genital tract. Serial sectioning at 2-mm intervals of 100 consecutive total hysterectomy specimens revealed the presence of leiomyomas in 77% of cases. 3 The rate of hospitalization of women for ULMs is 3.0 per 1000 women-years in the USA. Around 200 000 hysterectomies and 30 000 myomectomies Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access OESTROGEN DEPENDENCY OF ULMSThere is plenty of clinical and research evidence that ULMs are oestrogen-dependent tumours. The risk of developing ULMs increases with age during the premenopausal years; however, tumours typically regress and/or become asymptomatic with the onset of menopause. 6 Obesity, age at menarche and unopposed oestrogen exposure have been linked to an increased risk of ULMs, and cigarette smoking, use of oral contraceptives and parity have been identified as protective factors. 7 Moreover, using gonadotrophin-releasing hormone agonists leads to shrinkage of ULMs through the suppression of ovarian oestrogen production to postmenopausal levels. 8 At the molecular level, primary ULM cells express oestrogen receptors (OR) and progesterone receptors (PR). Rodent leiomyoma cells derived from the Eker rat model for this disease proliferate in response to oestrogen in cult...

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide. The tropism of HEV is not restricted to the liver, and the virus replicates in other organs. Not all the extrahepatic targets for HEV are identified. Herein, we found that non-decidualized primary human endometrial stromal cells (PHESCs), which are precursors for the decidua and placenta, are susceptible to HEV infection. PHESCs, isolated from healthy non-pregnant women (n = 5), were challenged with stool-derived HEV-1 and HEV-3. HEV RNA was measured by qPCR, and HEV capsid protein was assessed by flow cytometry, immunofluorescence (IF), and ELISA. HEV infection was successfully established in PHESCs. Intracellular and extracellular HEV RNA loads were increased over time, indicating efficient replication in vitro. In addition, HEV capsid protein was detected intracellularly in the HEV-infected PHESCs and accumulated extracellularly over time, confirming the viral assembly and release from the infected cells. HEV-1 replicated more efficiently in PHESCs than HEV-3 and induced more inflammatory responses. Ribavirin (RBV) treatment abolished the replication of HEV in PHESCs. In conclusion, PHESCs are permissive to HEV infection and these cells could be an endogenous source of HEV infection during pregnancy and mediate HEV vertical transmission.