Endometrial calbindins are critical for embryo implantation: Evidence from<i>in vivo</i>use of morpholino antisense oligonucleotides

Luu, K.; Nie, Guiying; Salamonsen, Lois A.

doi:10.1073/pnas.0401069101

Cited by 77 publications

(83 citation statements)

References 33 publications

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“…Calcium regulation at the endometrial-embryo interface is thought to be a potential important physiological response during this process (Li et al 2002, Wang et al 2003, Luu et al 2004. However, the molecules and pathways involved in the calcium homeostasis regulation are far away from being well elaborated.…”

Section: Introductionmentioning

confidence: 99%

Extracellular Ca2+-sensing receptor expression and hormonal regulation in rat uterus during the peri-implantation period

Xiao¹,

Yuan²,

Li³

et al. 2005

Reproduction

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The extracellular Ca 21 -sensing receptor (CaR) is a member of the superfamily of G protein-coupled receptors (GPCRs). It is an important mediator of a wide range of Ca 21 -dependent physiological responses in various tissues. In reproductive tissues it has been reported to play a significant role in promoting or maintaining placentation. Meanwhile, another Ca 21 regulated gene stanniocalcin-1 (STC-1) has been documented to be involved in decidualization and uterine remodelling. The phenomenon that CaR mediates STC-1's transcription responding to extracellular calcium in fish urges us to suppose that CaR, like STC-1, may also play a role in implantation and decidualization. To resolve this conjecture, we have examined the expression and hormonal regulation of the CaR gene in rat uterus during peri-implantation period. CaR mRNA was expressed at a moderate level in the luminal epithelium of the early stage of pregnancy (from day 1 to day 3). From day 2-3 it began to be expressed more strongly in the stromal cells immediately underneath the luminal epithelium, but decreased to a basal level on day 4. From day 6 to day 9 continuously, both CaR mRNA and protein were highly expressed in the primary decidua. Expression of CaR mRNA and protein in these cells was also observed when a delayed implantation was terminated by estrogen treatment to allow the embryo implantation. In contrast, only basal level expression of the molecules was detected in the cells of animals subjected to a normal-delayed implantation or the pseudopregnant condition. Embryo transplantation experiment confirmed that CaR expression at the implantation site was induced by the implanting blastocyst. Consistent with the normal pregnant process, CaR mRNA and protein in the cells were also induced by an artificial decidualization procedure. Further experiments demonstrated that treatment of the ovariectomized rat with estrogen or/and progesterone stimulated a high level expression of CaR mRNA in the uterine epithelial and glandular epithelium. In conclusion, CaR was specifically induced during the processes of implantation and subsequent decidualization and may play a role in these processes.Reproduction (2005) 129 779-788

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Section: Introductionmentioning

confidence: 99%

Extracellular Ca2+-sensing receptor expression and hormonal regulation in rat uterus during the peri-implantation period

Xiao¹,

Yuan²,

Li³

et al. 2005

Reproduction

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“…In situ hybridization localized the mRNA predominantly in the luminal epithelium and this luminal expression was downregulated specifically at the site of embryo contact (Nie et al 2000). The expression pattern and cellular localization of CaBP-d28k protein in the mouse uterus was found to be very similar to that of CaBP-d9k, suggesting that these two proteins might exert similar functions in the mouse uterus (Luu 2004). Recently, by using wildtype and CaBP-d28k null mice, as well as morpholino antisense oligonucleotides, we have demonstrated that embryo implantation cannot occur in the mouse uterus during early pregnancy when both CaBP-d9k and CaBP-d28k proteins are absent, but is unaffected when either calbindin is present (Luu 2004).…”

Section: Introductionmentioning

confidence: 84%

“…The expression pattern and cellular localization of CaBP-d28k protein in the mouse uterus was found to be very similar to that of CaBP-d9k, suggesting that these two proteins might exert similar functions in the mouse uterus (Luu 2004). Recently, by using wildtype and CaBP-d28k null mice, as well as morpholino antisense oligonucleotides, we have demonstrated that embryo implantation cannot occur in the mouse uterus during early pregnancy when both CaBP-d9k and CaBP-d28k proteins are absent, but is unaffected when either calbindin is present (Luu 2004). These results indicate that, in the mouse, uterine calbindins play critical roles at implantation, but that they have overlapping functions.…”

Section: Introductionmentioning

confidence: 86%

“…We have previously established that CaBP-d9k or CaBPd28k are essential for successful embryo implantation in the mouse uterus where these two proteins have overlapping functions (Luu 2004). We therefore hypothesized that one or both of these proteins would be expressed in the primate endometrium and contribute to the complex events of implantation.…”

Section: Discussionmentioning

confidence: 99%

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Endometrial expression of calbindin (CaBP)-d28k but not CaBP-d9k in primates implies evolutionary changes and functional redundancy of calbindins at implantation

et al. 2004

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The endometrium is hostile to embryo implantation except during the 'window of receptivity'. A change in endometrial gene expression is required for the development of receptivity. Calbindin-d9k (CaBP-d9k) and calbindin-d28k (CaBP-d28k) are proteins possessing EF-hand motifs which have high affinity for Ca 21 ions. Previously, it has been demonstrated that, in mouse endometrium, the expression of both calbindins is highly regulated during implantation and that both proteins play critical but functionally redundant roles at implantation. This study was the first to determine the expression of these two calbindins in the human and rhesus monkey endometrium. Initial RT-PCR analysis demonstrated that CaBP-d28k but not CaBP-d9k mRNA expression is detectable in the endometrium of both species. Western blot analysis confirmed the presence of immunoreactive CaBP-d28k protein in the primate endometrium. Furthermore, the endometrial expression pattern of CaBP-d28k mRNA and protein was examined by Northern blot analysis and immunohistochemistry respectively in both species across the menstrual cycle and during early pregnancy. Semi-quantitative statistical analysis of the immunohistochemistry results revealed that, in the human, CaBP-d28k protein expression was maximal in luminal and glandular epithelium during the mid-secretory phase, coinciding with the time when the endometrium is receptive to embryo implantation. Expression in rhesus monkey showed a similar trend. These results suggest that, in the primate endometrium, only CaBP-d28k is expressed and that the specific regulation of this calbindin is potentially important for the establishment of uterine receptivity.

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“…CaBP-9k and CaBP-28k are essential factors for early embryo implantation [16][17][18] and are affected by the sex steroid hormones E2 and P4. CaBP-9k expression is increased by E2 and P4 at estrus in rats but unaffected at diestrus in mice [1,11].…”

Section: Discussionmentioning

confidence: 99%

Duodenal and Renal Transient Receptor Potential Vanilloid 6 Is Regulated by Sex Steroid Hormones, Estrogen and Progesterone, in Immature Rats

Jung

Kim

Yang

et al. 2011

The Journal of Veterinary Medical Science

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ABSTRACT. Transient receptor potential vanilloid 6 (TRPV6) is a major calcium channel located in the apical and basolateral membranes of cells and distributed widely in many other organs, especially the exocrine tissues, intestine and uterus. Uterine TRPV6 is affected by sex steroid hormonal changes during the estrous cycle and pregnancy. To determine whether sex steroid hormones influence the expression of TRPV6 in other tissues, we further examined TRPV6 mRNA expression in the duodenum and kidney by reverse transcriptase and real-time PCRs and its protein levels by Western blot analysis and immunohistochemistry (IHC). Immature rats were injected with 17-estradiol (E2; 40 g/kg) and/or progesterone (P4; 4 mg/kg) for three days. Treatment with a mixture of E2 and P4 (E2/P4) increased TRPV6 expression in the duodenum, and this increase was maintained when the rats were treated with receptor antagonists of estrogen (ICI 182,780; 10 mg/kg) or progesterone (RU 486; 10 mg/kg) 30 min before E2/P4 injection. However, no difference was observed in renal TRPV6 protein levels following the treatment with sex steroid hormones and/or antagonists by Western blot analysis and IHC. These results suggest that duodenal TRPV6 expression may be induced by E2 combined with P4, whereas the renal TRPV6 level is unaffected by these steroids.KEY WORDS: duodenum, immature rats, kidney, transient receptor potential vanilloid 6 (TRPV6).J. Vet. Med. Sci. 73(6): 711-716, 2011 Calcium, the most abundant cation ion in the human body, is involved in organizing the bones and teeth and working in the extra-and intracellular fluids. As a universal intracellular messenger, calcium ion modulates neurotransmission, muscle constructions and secretion. Calcium ion enters the cell through the tight junctions between epithelial cells or through the apical and basolateral cell membranes. Calcium ion removal from epithelial cells requires apical calcium entry channels, including the intracellular calcium binding protein calbindin-D 9k , and the calcium pump plasma membrane calcium ATPase (PMCA1b) [5,10,13]. Transcellular calcium transport occurs through apical transient receptor potential vanilloid (TRPV) calcium channels [21]. The intestine, kidney and placenta are the three major organs implicated in calcium transport by calcium absorption from the diet, renal reabsorption and calcium transport from the maternal to fetal circulation, respectively [5]. In particular, maintenance of the uterine calcium balance is of crucial importance for many physiological functions, including smooth muscle contraction and embryo implantation. To obtain the calcium ion levels required for pregnancy and labor, the body uses numerous calcium transport genes, including CaBPs, PMCA and TRPVs [10,13]. These genes are regulated by various factors, i.e., vitamin D, dietary calcium ion and steroid hormones, and many reports have shown the expression of TRPV6 gene during the estrous cycle and pregnancy [3,6,[28][29][30].The actions of sex steroid hormones, i.e., estrogen (E2)...

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Endometrial calbindins are critical for embryo implantation: Evidence fromin vivouse of morpholino antisense oligonucleotides

Cited by 77 publications

References 33 publications

Extracellular Ca2+-sensing receptor expression and hormonal regulation in rat uterus during the peri-implantation period

Extracellular Ca2+-sensing receptor expression and hormonal regulation in rat uterus during the peri-implantation period

Endometrial expression of calbindin (CaBP)-d28k but not CaBP-d9k in primates implies evolutionary changes and functional redundancy of calbindins at implantation

Duodenal and Renal Transient Receptor Potential Vanilloid 6 Is Regulated by Sex Steroid Hormones, Estrogen and Progesterone, in Immature Rats

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