Exposure of pregnant sows to low doses of estradiol-17ß impacts on the transcriptome of the endometrium and the female preimplantation embryos.
Biol Reprod
; 100(3): 624-640, 2019 03 01.
Article
en En
| MEDLINE
| ID: mdl-30260370
ABSTRACT
Maternal exposure to estrogens can induce long-term adverse effects in the offspring. The epigenetic programming may start as early as the period of preimplantation development. We analyzed the effects of gestational estradiol-17ß (E2) exposure with two distinct low doses, corresponding to the acceptable daily intake "ADI" and close to the no-observed-effect level "NOEL", and a high dose (0.05, 10, and 1000 µg E2/kg body weight daily, respectively). The E2 doses were orally applied to sows from insemination until sampling at day 10 of pregnancy and compared to carrier-treated controls leading to a significant increase in E2 in plasma, bile and selected somatic tissues including the endometrium in the high-dose group. Conjugated and unconjugated E2 metabolites were as well elevated in the NOEL group. Although RNA-sequencing revealed a dose-dependent effect of 14, 17, and 27 differentially expressed genes (DEG) in the endometrium, single embryos were much more affected with 982 DEG in female blastocysts of the high-dose group, while none were present in the corresponding male embryos. Moreover, the NOEL treatment caused 62 and 3 DEG in female and male embryos, respectively. Thus, we detected a perturbed sex-specific gene expression profile leading to a leveling of the transcriptome profiles of female and male embryos. The preimplantation period therefore demonstrates a vulnerable time window for estrogen exposure, potentially constituting the cause for lasting consequences. The molecular fingerprint of low-dose estrogen exposure on developing embryos warrants a careful revisit of effect level thresholds.
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Texto completo:
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Banco de datos:
MEDLINE
Asunto principal:
Porcinos
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Blastocisto
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Endometrio
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Estradiol
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Transcriptoma
Límite:
Animals
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Pregnancy
Idioma:
En
Año:
2019
Tipo del documento:
Article