Etiology and pathogenesis of uterine leiomyomas: a review.

Flake, Gordon P.; Andersen, Jessica L.; Dixon, Darlene

doi:10.1289/ehp.5787

Cited by 496 publications

(432 citation statements)

References 280 publications

(353 reference statements)

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“…1 Aetiologies of uterine leiomyomas are unknown but several predisposing factors have been identified including age (late reproductive years), African-American ethnicity, nulliparity, obesity and genetics. 2 It is seven times commoner in blacks compared to Caucasians 3 and can grow so large to cause negative impact on obstetric outcome if co-existing with pregnancy. Estrogen is recognized as promoter of tumour growth.…”

Section: Introductionmentioning

confidence: 99%

Sonographic assessment of pregnancy co-existing with uterine leiomyoma in Owerri, Nigeria

Eze¹,

Odumeru²,

Ochie³

et al. 2013

Afr H. Sci.

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Background: Uterine myomas co-existing with pregnancy could cause obstetric complications. Objectives: To assess sonographically the frequency of occurrence and effect of uterine myomas co-existing with pregnancy. Methods: A longitudinal study was conducted during a period of 23 months. A convenience sample of 816 consecutive consenting pregnant women who met the inclusion criteria was evaluated during routine prenatal ultrasound scan. The women were referred for prenatal sonography. One hundred of the subjects who had myoma co-existing with pregnancy and another 100 subjects without myoma were selected for follow-up. These groups were followed up till delivery and obstetric complications and outcomes were documented. Any changes in size and growth rate of myoma were documented. Results: Subjects with myoma co-existing with pregnancy were 12.3%. This was commoner with increasing maternal age. An increase was observed in myoma mean size from 60mm to 63mm from the 1 st scan sequence to the 2 nd scan sequence and a reduction from 63mm to 59mm in the 3 rd scan sequence. Myoma growth rate was 0.667mm per week. Myomas in pregnancy especially large ones caused more complications during delivery when compared to pregnancies without myomas. Conclusion: Routine sonography is important in pregnancy management of uterine myomas co-existing with pregnancy.

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Section: Introductionmentioning

confidence: 99%

Sonographic assessment of pregnancy co-existing with uterine leiomyoma in Owerri, Nigeria

Eze¹,

Odumeru²,

Ochie³

et al. 2013

Afr H. Sci.

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“…The factors related to tumorigenesis of leiomyomata can be categorized as risk factors, initiators, promoters, and effectors. 1 The causes of leiomyomata (initiators) remain unknown. Most identified leiomyomata-associated factors, such as local growth factors, ER, PR and nonrandom chromosomal alterations were considered to be promoters or effectors.…”

mentioning

confidence: 99%

“…Most identified leiomyomata-associated factors, such as local growth factors, ER, PR and nonrandom chromosomal alterations were considered to be promoters or effectors. 1 Some growth factors have been shown to be overexpressed in leiomyomata, and are hormonally regulated both in vivo and in vitro. These factors are either autocrine or paracrine, which promote mitogenic and fibrogenic action in these tissues.…”

mentioning

confidence: 99%

Expression profile of tuberin and some potential tumorigenic factors in 60 patients with uterine leiomyomata

et al. 2005

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Human uterine leiomyomata are the most common tumors in women of reproductive age. The pathogenesis of leiomyomata remains unknown. An animal model of Eker rats with deleted tuberous sclerosis complex gene 2 (tuberin) shows increased incidence of leiomyomata. The role of tuberin in human leiomyomata is unknown. In this study, we designed a tissue microarray with tissue cores of leiomyomata and the matched myometrium from 60 hysterectomy specimens. We examined the expression of tuberin and tuberous sclerosis complex gene 1 product hamartin, proteins of the insulin-signaling pathway, steroid receptors and some of their cofactors, and human mobility group gene A2 by immunohistochemistry. We found that nearly half of the cases displayed either reduction or loss of tuberin in leiomyomata compared with matched normal myometrium. No change of hamartin was noted. Furthermore, a significant reduction of glucocorticoid receptor was found in leiomyomata with reduced tuberin. The proteins insulin like growth factor 1, insulin-like growth factor receptor b, AKT kinase, and phosphatidylinositol 3-kinase were upregulated. Nearly half of leiomyomata show upregulation of human mobility group gene A2, along with the steroid receptor cofactors. Our findings suggest that there are two broad groups of uterine leiomyomata. One group is associated with an alteration of tuberin and glucocorticoid receptor. The other group is associated with upregulation of human mobility group gene A2 and steroid receptor cofactors.

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“…First, although the endometrial lining is not shed, the porcine estrous cycle occurs approximately every 21 days, and lasts for about 2-3 days, the duration of which more closely approximates menses observed in women compared to the rodent estrous cycle (Yuan and Carlson, 1987;The Merck Veterinary Manual, 8th ed., 1998;Swindle, 1998;Andersen et al, 2002b). This cyclicity of hormonal influences seems to play an important role in the development of uterine fibroids in women (Cramer et al, 1995;Andersen et al, 2002a;Flake et al, 2003), making the potbellied pig an appropriate model in this respect.…”

Section: Discussionmentioning

confidence: 99%

“…Epidemiological studies suggest that hormonal influences play a significant role, due in part to continuous menstrual cycling (Flake et al, 2003). Molecular studies have identified differences in hormone receptor expression and further support a hormonemediated mechanism (Flake et al, 2003). Unfortunately, the lack of a suitable animal model has made it difficult to further elucidate the pathogenesis of fibroid formation, including the role of xenoestrogens in uterine leiomyoma development.…”

Section: Introductionmentioning

confidence: 99%

Uterine Smooth Muscle Tumors in Potbellied Pigs (Sus scrofa) Resemble Human Fibroids: A Potential Animal Model

2004

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Uterine leiomyomas, commonly termed fibroids, clinically affect approximately 25% of women of reproductive age in the United States, with a subclinical incidence as high as 77%. The pathogenesis of fibroid formation remains poorly understood, due in large part to the lack of a suitable animal model. This retrospective study characterizes the clinical, gross, and histopathologic features of similar, spontaneously occurring uterine tumors in potbellied pigs. Medical records available through a local Potbellied Pig Spay/Neuter Program, pig sanctuaries, and the Duchess Fund database were reviewed for evidence of reproductive disease or surgery. One-hundred and six female potbellied pigs were evaluated and uterine neoplasia was identified in 17 animals; tissues were available for 13 of these. Uterine leiomyoma was diagnosed in 11 of 13 cases, leiomyosarcoma in 1 of 13 cases, and undifferentiated sarcoma in 1 case. Pigs presented with clinical signs including abdominal distension or vaginal bleeding or were subclinical and identified during ovariohysterectomy. Tumors ranged from microscopic to 45 kg, were often multiple, and primarily involved the uterine horns. Hematoxylin and eosin and trichrome-stained sections were evaluated for morphological features of human and animal leiomyomas; immunohistochemistry to detect smooth muscle actin was also performed. The cellular pattern/morphology and variable degree of fibroplasia of the leiomyomas were similar to that reported for human fibroids. These results support further investigation of uterine leiomyomas in potbellied pigs as a potentially valuable animal model for studying human fibroids.

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Etiology and pathogenesis of uterine leiomyomas: a review.

Cited by 496 publications

References 280 publications

Sonographic assessment of pregnancy co-existing with uterine leiomyoma in Owerri, Nigeria

Sonographic assessment of pregnancy co-existing with uterine leiomyoma in Owerri, Nigeria

Expression profile of tuberin and some potential tumorigenic factors in 60 patients with uterine leiomyomata

Uterine Smooth Muscle Tumors in Potbellied Pigs (Sus scrofa) Resemble Human Fibroids: A Potential Animal Model

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