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Myeloid ecotropic viral integration site 1 (MEIS) 1 involvement in embryonic implantation.

Xu B, Geerts D, Qian K, Zhang H, Zhu G - Hum. Reprod. (2008)

Bottom Line: Analysis of an Affymetrix data set in the public domain showed high expression of MEIS1 in human endometrium.MEIS1 expression was confirmed during the human menstrual cycle by RT-PCR and in situ hybridization and was increased during the secretory compared with proliferative phase of the cycle (P = 0.0001), the time of implantation.Increased or decreased Meis1 expression significantly increased or decreased the expression of integrin beta3, a transcriptional target of HOXA10 and an important factor in early embryo-endometrium interactions (P = 0.006).

View Article: PubMed Central - PubMed

Affiliation: Reproductive Medicine Center, Tongji Hospital, Tongji Medicine College, Huazhong, University of Science and Technology, 1095 JieFang Avenue, Wuhan 430030, People's Republic of China.

ABSTRACT

Background: The HOXA10 homeobox gene controls embryonic uterine development and adult endometrial receptivity. The three-amino-acid loop extension (TALE) family homeobox genes like myeloid ecotropic viral integration site 1 (MEIS) provide enhanced target gene activation and specificity in HOX-regulated cellular processes by acting as HOX cofactors.

Methods and results: Analysis of an Affymetrix data set in the public domain showed high expression of MEIS1 in human endometrium. MEIS1 expression was confirmed during the human menstrual cycle by RT-PCR and in situ hybridization and was increased during the secretory compared with proliferative phase of the cycle (P = 0.0001), the time of implantation. To assess the importance of maternal Meis1 expression in a mouse model, the uteri of Day 2 pregnant mice were injected with Meis1 over-expression or small interfering RNA (siRNA) constructs. Blocking Meis1 expression by siRNA before implantation significantly reduced average implantation rates (P = 0.00001). Increased or decreased Meis1 expression significantly increased or decreased the expression of integrin beta3, a transcriptional target of HOXA10 and an important factor in early embryo-endometrium interactions (P = 0.006). Manipulating Meis1 expression before implantation also dramatically affected the number of pinopodes, uterine endometrial epithelial projections that develop at the time of endometrial receptivity.

Conclusions: The results suggest that in mouse, meis1 contributes to regulating endometrial development during the menstrual cycle and establishing the conditions necessary for implantation.

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Effect of Meis1 expression on mouse litter size.Litter size, as determined by counting the number of implantation sites per uterus examined, at Day 9 of pregnancy. Mice were transfected 1 day after detection of a vaginal plug with pTER/Meis1, control pTER, pcDNA4/MEIS1 or empty pcDNA4. (a) Litter size was reduced by 40% in the group of mice transfected with pTER/Meis1 siRNA compared with pTER controls. This difference was statistically significant according to a two-tailed unpaired t-test (P = 0.00001). (b) Litter size at Day 9 of gestation was not affected by transfection with pcDNA4/MEIS1 compared with pcDNA4-transfected controls (P = 0.08). The experiment was repeated three times, with similar results
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DEN082F5: Effect of Meis1 expression on mouse litter size.Litter size, as determined by counting the number of implantation sites per uterus examined, at Day 9 of pregnancy. Mice were transfected 1 day after detection of a vaginal plug with pTER/Meis1, control pTER, pcDNA4/MEIS1 or empty pcDNA4. (a) Litter size was reduced by 40% in the group of mice transfected with pTER/Meis1 siRNA compared with pTER controls. This difference was statistically significant according to a two-tailed unpaired t-test (P = 0.00001). (b) Litter size at Day 9 of gestation was not affected by transfection with pcDNA4/MEIS1 compared with pcDNA4-transfected controls (P = 0.08). The experiment was repeated three times, with similar results

Mentions: Nulliparous female and male Kunming mice of reproductive age were supplied by Center of Experimental Animals, Tongji Medical College (Wuhan, China). Female mice were mated and examined every 8 h until detection of a vaginal plug, which was designated Day 1 of the pregnancy. The mice were anesthetized 30–60 h following plug detection with 1% butaylone given by i.p. injection. A laparotomy was performed to expose the uterus and 25 µl of the DNA/liposome complex was injected into the base of each uterine horn using a 27-gage needle, as described (Bagot et al., 2000; Hsieh et al., 2002). The incision was closed in two layers (peritoneal and cutaneous) with 4–0 vicryl suture. The mice were euthanized by cervical vertebrae dislocation under anesthesia before excision of the uteri. For the experiments studying the effect of MEIS1 expression manipulation on MEIS1 expression, litter size and pinopode formation, the group sizes were five mice each transfected with pcDNA4/MEIS1, empty pcDNA4, pTER/Meis1 siRNA construct or non-targeting pTER, respectively (20 mice in total). For the experiments studying the effect of MEIS1 expression manipulation on Itgb3 expression, 25 mice each were transfected with pcDNA4/MEIS1, empty pcDNA4, pTER/Meis1 siRNA construct or non-targeting pTER, respectively (100 mice in total). The numbers of mice available for Meis1 expression analysis in Fig. 5 were 19, 17, 19 and 19, respectively (the remainder were not pregnant in spite of the detection of the vaginal plug or died of post-surgical complications). The presented work conformed to the ‘Guiding principles in the Care and Use of Animals’ as described in DHEW publication No. (NIH) 85-23, Revised 1985, Office of Science and Health Reports, DRR/NIH, Bethesda, MD 20982, USA, was approved by the ethical committee of Tongji Medical College and was also covered by Chinese animal husbandry legislation.


Myeloid ecotropic viral integration site 1 (MEIS) 1 involvement in embryonic implantation.

Xu B, Geerts D, Qian K, Zhang H, Zhu G - Hum. Reprod. (2008)

Effect of Meis1 expression on mouse litter size.Litter size, as determined by counting the number of implantation sites per uterus examined, at Day 9 of pregnancy. Mice were transfected 1 day after detection of a vaginal plug with pTER/Meis1, control pTER, pcDNA4/MEIS1 or empty pcDNA4. (a) Litter size was reduced by 40% in the group of mice transfected with pTER/Meis1 siRNA compared with pTER controls. This difference was statistically significant according to a two-tailed unpaired t-test (P = 0.00001). (b) Litter size at Day 9 of gestation was not affected by transfection with pcDNA4/MEIS1 compared with pcDNA4-transfected controls (P = 0.08). The experiment was repeated three times, with similar results
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2387222&req=5

DEN082F5: Effect of Meis1 expression on mouse litter size.Litter size, as determined by counting the number of implantation sites per uterus examined, at Day 9 of pregnancy. Mice were transfected 1 day after detection of a vaginal plug with pTER/Meis1, control pTER, pcDNA4/MEIS1 or empty pcDNA4. (a) Litter size was reduced by 40% in the group of mice transfected with pTER/Meis1 siRNA compared with pTER controls. This difference was statistically significant according to a two-tailed unpaired t-test (P = 0.00001). (b) Litter size at Day 9 of gestation was not affected by transfection with pcDNA4/MEIS1 compared with pcDNA4-transfected controls (P = 0.08). The experiment was repeated three times, with similar results
Mentions: Nulliparous female and male Kunming mice of reproductive age were supplied by Center of Experimental Animals, Tongji Medical College (Wuhan, China). Female mice were mated and examined every 8 h until detection of a vaginal plug, which was designated Day 1 of the pregnancy. The mice were anesthetized 30–60 h following plug detection with 1% butaylone given by i.p. injection. A laparotomy was performed to expose the uterus and 25 µl of the DNA/liposome complex was injected into the base of each uterine horn using a 27-gage needle, as described (Bagot et al., 2000; Hsieh et al., 2002). The incision was closed in two layers (peritoneal and cutaneous) with 4–0 vicryl suture. The mice were euthanized by cervical vertebrae dislocation under anesthesia before excision of the uteri. For the experiments studying the effect of MEIS1 expression manipulation on MEIS1 expression, litter size and pinopode formation, the group sizes were five mice each transfected with pcDNA4/MEIS1, empty pcDNA4, pTER/Meis1 siRNA construct or non-targeting pTER, respectively (20 mice in total). For the experiments studying the effect of MEIS1 expression manipulation on Itgb3 expression, 25 mice each were transfected with pcDNA4/MEIS1, empty pcDNA4, pTER/Meis1 siRNA construct or non-targeting pTER, respectively (100 mice in total). The numbers of mice available for Meis1 expression analysis in Fig. 5 were 19, 17, 19 and 19, respectively (the remainder were not pregnant in spite of the detection of the vaginal plug or died of post-surgical complications). The presented work conformed to the ‘Guiding principles in the Care and Use of Animals’ as described in DHEW publication No. (NIH) 85-23, Revised 1985, Office of Science and Health Reports, DRR/NIH, Bethesda, MD 20982, USA, was approved by the ethical committee of Tongji Medical College and was also covered by Chinese animal husbandry legislation.

Bottom Line: Analysis of an Affymetrix data set in the public domain showed high expression of MEIS1 in human endometrium.MEIS1 expression was confirmed during the human menstrual cycle by RT-PCR and in situ hybridization and was increased during the secretory compared with proliferative phase of the cycle (P = 0.0001), the time of implantation.Increased or decreased Meis1 expression significantly increased or decreased the expression of integrin beta3, a transcriptional target of HOXA10 and an important factor in early embryo-endometrium interactions (P = 0.006).

View Article: PubMed Central - PubMed

Affiliation: Reproductive Medicine Center, Tongji Hospital, Tongji Medicine College, Huazhong, University of Science and Technology, 1095 JieFang Avenue, Wuhan 430030, People's Republic of China.

ABSTRACT

Background: The HOXA10 homeobox gene controls embryonic uterine development and adult endometrial receptivity. The three-amino-acid loop extension (TALE) family homeobox genes like myeloid ecotropic viral integration site 1 (MEIS) provide enhanced target gene activation and specificity in HOX-regulated cellular processes by acting as HOX cofactors.

Methods and results: Analysis of an Affymetrix data set in the public domain showed high expression of MEIS1 in human endometrium. MEIS1 expression was confirmed during the human menstrual cycle by RT-PCR and in situ hybridization and was increased during the secretory compared with proliferative phase of the cycle (P = 0.0001), the time of implantation. To assess the importance of maternal Meis1 expression in a mouse model, the uteri of Day 2 pregnant mice were injected with Meis1 over-expression or small interfering RNA (siRNA) constructs. Blocking Meis1 expression by siRNA before implantation significantly reduced average implantation rates (P = 0.00001). Increased or decreased Meis1 expression significantly increased or decreased the expression of integrin beta3, a transcriptional target of HOXA10 and an important factor in early embryo-endometrium interactions (P = 0.006). Manipulating Meis1 expression before implantation also dramatically affected the number of pinopodes, uterine endometrial epithelial projections that develop at the time of endometrial receptivity.

Conclusions: The results suggest that in mouse, meis1 contributes to regulating endometrial development during the menstrual cycle and establishing the conditions necessary for implantation.

Show MeSH
Related in: MedlinePlus