HOX gene expression is altered in the endometrium of women with endometriosis

Taylor, Hugh S.; Bagot, Catherine; Kardana, Andrew; Olive, David L.; Arıcı, Aydın

doi:10.1093/humrep/14.5.1328

Cited by 354 publications

(263 citation statements)

References 30 publications

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“…Hoxa10 antisense treatment reduces maternal Hoxa10 expression and reduces litter size, demonstrating that maternal Hoxa10 is necessary for endometrial receptivity to blastocyst implantation. Similarly, in humans with endometriosis and decreased implantation rates, maternal uterine HOXA10 is also decreased (Taylor et al, 1999). This finding suggests a similar role in human endometrial development and receptivity to implantation.…”

Section: Introductionmentioning

confidence: 62%

Maternal Hoxa10 is required for pinopod formation in the development of mouse uterine receptivity to embryo implantation

2001

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Hoxa10 is a homeobox gene that is expressed both during the embryogenesis of the genitourinary tract and in the adult reproductive tract. Maternal Hoxa10 expression is necessary for endometrial receptivity to blastocyst implantation. The mechanism by which Hoxa10 induces endometrial development to a state of receptivity is unknown as HOXA10-deficient endometrium appears histologically normal. We altered the expression of Hoxa10 in the uterus of cycling adult female mice and examined the uterus at the time of implantation by transmission electron microscopy for alterations in epithelial morphology. Pinopods are projections on the surface of the uterine endometrial epithelial cells that develop transiently at the time of endometrial receptivity. Blocking Hoxa10 expression by transfection of Hoxa10 antisense into the cycling mouse uterus before implantation dramatically decreased pinopod number. Constitutively expressing Hoxa10 in the uterus just before the normal time of pinopod formation resulted in increased pinopod number. Therefore, Hoxa10 is necessary for pinopod development. Hox genes have been implicated in both the regulation of cellular proliferation and the determination of developmental fate. Hoxa10 exemplifies this dual role in the uterus by regulating both endometrial stromal cell proliferation and epithelial cell morphogenesis. Taken together, these results demonstrate that maternal Hoxa10 has an essential role in pinopod development and this function of Hoxa10 likely contributes to endometrial receptivity for the purpose of blastocyst implantation.

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Section: Introductionmentioning

confidence: 62%

Maternal Hoxa10 is required for pinopod formation in the development of mouse uterine receptivity to embryo implantation

2001

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“…6 However, indirect evidence has suggested a role for maternal Hoxa10 expression in implantation. 10,14 We have previously shown that four genes of the HOXA cluster demonstrate continued expression in the adult reproductive tract. 5 Furthermore, we have shown that HOXA10 is expressed in the adult endometrium in a dynamic way that varies with the menstrual cycle suggesting a role for maternal HOXA10 in implantation.…”

Section: Discussionmentioning

confidence: 99%

“…We have previously shown that, based on the rise in HOXA10 expression at the time of implantation, maternal HOXA10 is probably similarly required for this process in women. 7,10 The alteration of human HOXA10 expression in the adult endometrium is a potential contraceptive agent or fertility treatment.…”

Section: Introductionmentioning

confidence: 99%

Alteration of maternal Hoxa10 expression by in vivo gene transfection affects implantation

2000

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Mice with a targeted mutation of the Hoxa10 gene demonstrate uterine factor infertility. It is unclear if the defect in the uterine environment arises due to the absence of Hoxa10 expression during embryonic development or in the adult. We have recently demonstrated that HOXA10 expression in human endometrium rises dramatically at the time of implantation, suggesting maternal expression of Hoxa10/HOXA10 may be essential to the process. To assess the importance of maternal Hoxa10 expression, the uteri of day 2 pregnant mice were injected with a DNA/liposome complex containing constructs designed to alter maternal Hoxa10 expression before implantation. Transfection with a Hoxa10 antisense oligodeoxyribonucleotide significantly decreased the number

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“…In humans, the expression of both HOXA10 and HOXA11 rises dramatically during the implantation window and remains elevated throughout the secretory phase. However, patients with endometriosis do not show this rise in HOXA10 and HOXA11 (Taylor et al 1999a;Kim et al 2007;Lee et al 2009). …”

Section: Hox Genes and Endometriosismentioning

confidence: 94%

The Role ofHoxGenes in Female Reproductive Tract Development, Adult Function, and Fertility

Taylor

2015

Cold Spring Harb Perspect Med

196

158

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HOX genes convey positional identity that leads to the proper partitioning and adult identity of the female reproductive track. Abnormalities in reproductive tract development can be caused by HOX gene mutations or altered HOX gene expression. Diethylstilbestrol (DES) and other endocrine disruptors cause Mü llerian defects by changing HOX gene expression. HOX genes are also essential regulators of adult endometrial development. Regulated HOXA10 and HOXA11 expression is necessary for endometrial receptivity; decreased HOXA10 or HOXA11 expression leads to decreased implantation rates. Alternation of HOXA10 and HOXA11 expression has been identified as a mechanism of the decreased implantation associated with endometriosis, polycystic ovarian syndrome, leiomyoma, polyps, adenomyosis, and hydrosalpinx. Alteration of HOX gene expression causes both uterine developmental abnormalities and impaired adult endometrial development that prevent implantation and lead to female infertility.

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HOX gene expression is altered in the endometrium of women with endometriosis

Cited by 354 publications

References 30 publications

Maternal Hoxa10 is required for pinopod formation in the development of mouse uterine receptivity to embryo implantation

Maternal Hoxa10 is required for pinopod formation in the development of mouse uterine receptivity to embryo implantation

Alteration of maternal Hoxa10 expression by in vivo gene transfection affects implantation

The Role ofHoxGenes in Female Reproductive Tract Development, Adult Function, and Fertility

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