Retinoic acid decreases the viability of mouse blastocysts in vitro

Huang, Fay; Shen, Chung‐Chang; Chang, Shiuh‐Young; Wu, Tsu‐Juey; Hsuuw, Yan‐Der

doi:10.1093/humrep/deg018

Cited by 56 publications

(49 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In cultured mouse blastocysts, the antiproliferative and pro-apoptotic effects of 10 µm ATRA were mainly targeted to the ICM (Huang et al 2005). These studies did not contain protein in the medium and the high supraphysiological concentrations of ATRA used may explain why these detrimental effects of 10 µm ATRA in mice (Huang et al 2003) differ to the results obtained in the present study. In addition, there are important species-specific differences, because RARβ mRNA expression has been shown in mice (Wu et al 1981), but not in bovine blastocysts (Mohan et al 2001).…”

Section: Discussioncontrasting

confidence: 74%

See 1 more Smart Citation

127 Development and Quality of Bovine Morulae Cultured in Serum-Free Medium With Retinoic Receptor Specific Agonists

Gómez¹,

Caamaño²,

Muñoz³

et al. 2008

Reprod. Fertil. Dev.

View full text Add to dashboard Cite

Abstract.Retinoids regulate development and differentiation of the bovine blastocyst in vitro, although the underlying mechanisms remain to be clarified. A challenge in reproductive biotechnology is the identification of pathways that regulate early embryonic development and their influence on blastocyst differentiation, apoptosis and survival to cryopreservation as traits of embryo quality. The present paper analyses the effects of short-term exposure (24 h) to retinoids on in vitroproduced bovine morulae. Immature cumulus oocyte complexes were in vitro matured and fertilised. Presumptive zygotes were subsequently cultured in modified synthetic oviduct fluid up to Day 6, in which morulae were randomly allocated to the different experimental groups. The treatments consisted of 0.1 µm LG100268 (LG; a retinoid X receptor agonist), 0.7 µm all-trans retinoic acid (ATRA; a retinoic acid receptor agonist) or no additives. Day 8 blastocyst development was increased in the ATRA-treated group compared with the LG and untreated embryos. In Day 7 embryos, the number of total cells and cells allocated to the trophectoderm were higher in the ATRA-treated group compared with untreated embryos. Apoptosis in the inner cell mass increased after LG treatment, whereas ATRA had no effect. After vitrification and warming, survival and hatching rates of Day 7 blastocysts did not change with retinoid treatment. Within the LGtreated and untreated blastocyst groups, survival and hatching rates were higher for Day 7 than Day 8 embryos; however, Day 8 blastocysts treated with ATRA showed improved hatching rates. In conclusion, treatment of morulae with ATRA in serum-free medium improves embryo development and quality without increasing the incidence of apoptosis and necrosis.

show abstract

Section: Discussioncontrasting

confidence: 74%

“…In the mouse, exposure of blastocysts to excessATRA directly affects the ICM (Huang et al 2005), leading to adverse effects on development (Huang et al 2001(Huang et al , 2003.…”

Section: Discussionmentioning

confidence: 99%

127 Development and Quality of Bovine Morulae Cultured in Serum-Free Medium With Retinoic Receptor Specific Agonists

Gómez¹,

Caamaño²,

Muñoz³

et al. 2008

Reprod. Fertil. Dev.

View full text Add to dashboard Cite

show abstract

“…We previously reported that overexposure (48 h) of cattle oocytes to 9-cis-RA prior to fertilization reduced blastocyst rates, in contrast to oocytes incubated for 24 h with 9-cis RA either during meiotic inhibition or in vitro maturation [11,14,15]. The detrimental effects of high dosage were reported by Huang et al [16] in mice embryos exposed for 24 h to 10 mM ATRA. These authors found antiproliferative and pro-apoptotic effects that mainly targeted the ICM [17].…”

Section: Discussionmentioning

confidence: 88%

Retinoid receptor-specific agonists regulate bovine in vitro early embryonic development, differentiation and expression of genes related to cell cycle arrest and apoptosis

et al. 2007

View full text Add to dashboard Cite

A major goal in reproductive biotechnology is the identification of pathways that regulate early embryonic development and the allocation of cells to the inner cell mass (ICM) and trophectoderm (TE). Retinoids regulate the development and differentiation of the bovine blastocyst in vitro, although the involvement of the retinoid X receptors (RXRs) remains to be clarified. This paper compares the effect of a synthetic RXR agonist (LG100268; LG) with that of the retinoic acid receptor (RAR) agonist all-trans retinoic acid (ATRA) on blastulation. In vitro-produced morulae were treated for 48 h with LG (0.1 mM, 1 mM and 10 mM), ATRA 0.7 mM, or no additives. Treatment with ATRA did not increase the rate of development; however, the LG 0.1 mM treatment increased both the blastocyst development and hatching rate. Cell numbers increased in the ICM with LG 10 mM, while a dosedependent reduction was observed in the TE in the presence of LG. Gene expression levels of p53 and p66 did not vary with LG but increased with ATRA. Both LG and ATRA activated bax, a pro-apoptotic gene and H2A.Z, a cell cycle-related gene. The above effects suggest the existence of active p53-dependent and -independent apoptotic pathways for ATRA and LG, respectively, in the bovine embryo. The expression of p53 and H2A.Z showed a strong, positive correlation (r = 0.93; p < 0.0001) in all experimental groups; both proteins are linked through the cell cycle. Agonists of RXR could be used to control blastocyst development and differentiation. #

show abstract

“…Most studies on retinoids have focused on later stages of embryonic development, although exposure of zygotes to RA during early embryonic development yields anomalies during pre-gastrulation and organogenesis (Rutledge 1997). Recently, RA treatment during the pre-implantation period in the mouse (Huang et al 2001(Huang et al , 2003 was shown to cause developmental retardation, inhibition of cell proliferation and induction of apoptosis. In previous reports, development of blastocysts to term was not analysed (Shaw et al 1995, Whaley et al 1997, Eberhardt et al 1999, and the precise stage (oocyte, embryo or both) during which retinoids exerted their effects was not determined.…”

Section: Embryos Transferred Pregnancy (%)mentioning

confidence: 99%

Oocytes recovered from cows treated with retinol become unviable as blastocysts produced in vitro

Hidalgo¹,

Díez²,

Duque³

et al. 2005

Reproduction

View full text Add to dashboard Cite

Retinoids have been shown to enhance developmental competence of the oocyte in cattle, sheep and pigs. In this study we investigated whether exogenous retinol stimulates the bovine oocyte during its intrafollicular growth and the time limits of exposure to exogenous retinol. In addition, we also determined the efficiency of ovum pick-up techniques in combination with retinol treatment and the viability of embryos after transfer to recipients. In Experiment 1, heifers were injected with retinol or vehicle, and concentrations of retinol in the blood were analysed on Day 0 (prior to injection), Day 1 and, together with follicular fluid, Day 4. Blood retinol increased by Day 1 and cleared on Day 4, but retinol remained higher within the follicle. In Experiment 2, oocyte donors were injected weekly with retinol or vehicle four times during a twice-per-week cycle of eight recovery sessions (starting 4 days before the first session), followed by a second eight-session cycle without treatment. Oocytes recovered were fertilized and culturedin vitro.Retinol treatment yielded higher numbers of low-quality oocytes throughout, although retinol measured during cycles did not change. Total oocytes, and morulae and blastocyst rates, increased during the first five sessions following treatment with retinol. As previously shown with oocytes from slaughterhouse ovaries, retinoic acid stimulated blastocyst development. Following transfer to recipients, blastocysts from oocytes exposed to retinol were unable to establish pregnancy. Our study confirms the existence of an effect of retinol on the intrafollicular oocyte in the cow and provides evidence regarding the teratogenic effect of retinol.

show abstract

Retinoic acid decreases the viability of mouse blastocysts in vitro

Abstract: This is the first evidence that retinoic acid induces cell death (apoptosis) and inhibits cell proliferation in mouse blastocysts. This results in the retardation of early postimplantation blastocyst development and subsequent blastocyst death.

Cited by 56 publications

References 37 publications

127 Development and Quality of Bovine Morulae Cultured in Serum-Free Medium With Retinoic Receptor Specific Agonists

127 Development and Quality of Bovine Morulae Cultured in Serum-Free Medium With Retinoic Receptor Specific Agonists

Retinoid receptor-specific agonists regulate bovine in vitro early embryonic development, differentiation and expression of genes related to cell cycle arrest and apoptosis

Oocytes recovered from cows treated with retinol become unviable as blastocysts produced in vitro

Contact Info

Product

Resources

About