Expression of Hedgehog Family Genes in the Rat Uterus During Early Pregnancy

Kubota, Kaiyu; Yamauchi, Nobuhiko; Matsumoto, Kenji; Watanabe, Ryoji; Oozono, Shinji; Aramaki, Shigeto; Wood, Chris; Soh, Tomoki; Hattori, Masa Aki

doi:10.1262/jrd.20054

Cited by 8 publications

(16 citation statements)

References 28 publications

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“…On day 4, Ihh expression decreases in the luminal epithelium but remains high in the glandular epithelium . Patterns of Ihh expression in pregnant rats and hamsters are similar to that in the mouse (Khatua et al 2006, Kubota et al 2008. Treatment of ovariectomized mice with progesterone increased expression of Ihh in luminal and glandular epithelium , Takamoto et al 2002; the effect of progesterone was reduced in progesterone receptor (PGR) null mice (Takamoto et al 2002), providing evidence that Ihh is a target of signaling through PGR.…”

Section: Introductionmentioning

confidence: 78%

“…In addition, mRNA levels of Hhip and CouptfII, genes for which transcription is increased by HH signaling, were also elevated in the epithelium and periepithelial stroma (Takamoto et al 2002). In rats, the downstream target gene of HH signaling, Gli1, was expressed in the luminal epithelium as well as in the stroma on day 3.5 of pregnancy (Kubota et al 2008). In the current study, quantitative RT-PCR showed expression of components of the HH signaling pathway typical of target cells in luminal epithelium of uteri on day 4 of pregnancy.…”

Section: Discussionmentioning

confidence: 99%

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Reduced signaling through the hedgehog pathway in the uterine stroma causes deferred implantation and embryonic loss

Harman¹,

Cowan²,

Ren³

et al. 2011

Reproduction

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The role of the hedgehog (HH) signaling pathway in implantation was studied in mice in which the HH signal transducer, smoothened (SMO), was conditionally deleted in the stromal compartment of the uterus, using CRE recombinase expressed through the Amhr2 -mutant mice, Smo mRNA in uterine stroma was reduced 49% compared to that in Amhr2control mice, while levels in the luminal epithelium were not different. Litter size was reduced 60% in mutants compared with controls, but ovulation rate and the number of implantation sites on day 7 of pregnancy did not differ. The number of corpora lutea was equivalent to the number of implantation sites, indicating that most ovulations resulted in implanted embryos. However, on days 13 to 15, the rate of embryo resorption was elevated in mutants. In control mice, on day 5, implantation sites were present and blastocysts were well-attached. In contrast, blastocysts were readily flushed from uteri of mutant mice on day 5 and implantation sites were rare. On days 5.5 and 6, implantation sites were present in mutant mice, and by day 6 embryos could not be flushed from the uterus. The weight of implantation sites on day 7 was decreased by 42% in mutant mice, consistent with delayed development. Signaling through SMO in the endometrial stroma is required for optimal timing of implantation, and deferred implantation leads to defective embryo development and subsequent pregnancy loss.

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Section: Introductionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Reduced signaling through the hedgehog pathway in the uterine stroma causes deferred implantation and embryonic loss

Harman¹,

Cowan²,

Ren³

et al. 2011

Reproduction

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show abstract

“…In addition, similar to the mouse, expression of components of the HH signaling pathway increases around the time of implantation in rats (Kubota et al, 2008;Kubota et al, 2010) and hamsters (Khatua et al, 2006). In another experiment, pieces of uterus in which the luminal epithelium was enzymatically removed were cultured in vitro.…”

Section: Hedgehog Signaling Pathway and The Frtmentioning

confidence: 99%

“…and Gli transcription factors -in mice (Lee et al, 2006a;Matsumoto et al, 2002;Takamoto et al, 2002), hamsters (Khatua et al, 2006), rats (Katayama et al, 2006;Kubota et al, 2008;Kubota et al, 2010), and humans (Wei et al, 2010). Cre sequence was inserted into the Pgr locus (Franco et al, 2010b).…”

Section: Ptch1mentioning

confidence: 99%

“…In addition, expression of Ihh in the luminal and glandular epithelium of the uterus is increased in response to signaling though PGR (Khatua et al, 2006;Lee et al, 2006b;Matsumoto et al, 2002;Takamoto et al, 2002;Wakitani et al, 2008) and expression of Ihh in the epithelium increases before implantation (Kubota et al, 2008;Kubota et al, 2010;Lee et al, 2006a;Wakitani et al, 2008). Conditional deletion of Ihh in the mouse uterus blocked implantation (Franco et al, 2010;Lee et al, 2006a).…”

Section: Introductionmentioning

confidence: 99%

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Dominant Activation of Hedgehog Signaling Alters Development of the Female Reproductive Tract.

Migone

Ren

Harman

et al. 2010

Biology of Reproduction

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Dominant activation of the hedgehog signaling pathway alters development of the female reproductive tract

Migone

Ren

Cowan

et al. 2011

Genesis

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The role of hedgehog (HH) signaling in reproductive tract development was studied in mice in which a dominant active allele of the signal transducer smoothened (SmoM2) was conditionally expressed in the Müllerian duct and ovary. Mutant females are infertile, primarily because they fail to ovulate. Levels of mRNA for targets of HH signaling, Gli1, Ptch1, and Hhip, were elevated in reproductive tracts of 24-day-old mutant mice, confirming overactivation of HH signaling. The tracts of mutant mice developed abnormally. The uterine luminal epithelium had a simple columnar morphology in control mice, but in mutants contained stratified squamous cells typical of the cervix and vagina. In mutant mice, the number of uterine glands were reduced and the oviducts were not coiled. Expression of genes within the Hox and Wnt families that regulate patterning of the reproductive tract were altered. Hoxa13, which is normally expressed primarily in the vagina and cervix, was expressed at 12-fold higher levels in the uterus of mutant mice compared with controls. Wnt5a, which is required for development of the cervix and vagina and postnatal differentiation of the uterus, was expressed at higher levels in the oviduct and uterus of mutant mice compared with controls. Mating mutant females with fertile or vasectomized males induced a severe inflammatory response in the tract. In summary, overactivation of HH signaling causes aberrant development of the reproductive tract. The phenotype observed could be mediated by ectopic expression of Hoxa13 in the uterus and elevated levels of Wnt5a in the oviducts and uterus.

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Expression of Hedgehog Family Genes in the Rat Uterus During Early Pregnancy

Cited by 8 publications

References 28 publications

Reduced signaling through the hedgehog pathway in the uterine stroma causes deferred implantation and embryonic loss

Reduced signaling through the hedgehog pathway in the uterine stroma causes deferred implantation and embryonic loss

Dominant Activation of Hedgehog Signaling Alters Development of the Female Reproductive Tract.

Dominant activation of the hedgehog signaling pathway alters development of the female reproductive tract

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