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Impact of preimplantational oral low-dose estradiol-17β exposure on the endometrium: The role of miRNA


Flöter, Veronika L; Lorenz, Anne-Kathrin; Kirchner, Benedikt; Pfaffl, Michael W; Bauersachs, Stefan; Ulbrich, Susanne E (2018). Impact of preimplantational oral low-dose estradiol-17β exposure on the endometrium: The role of miRNA. Molecular Reproduction and Development, 85(5):417-426.

Abstract

Porcine conceptuses synthesize estrogens between Day 11 and 12 as signal for maternal recognition of pregnancy. A preimplantational estrogen exposure to pregnant gilts has been associated with embryonic losses and changes in endometrial mRNA expression. MicroRNAs (miRNAs) play a key role in the mRNA regulation by modulating the expression. Effects of estrogens on endometrial miRNAs have not been investigated in this context so far. Thus, we studied the endometrial expression profile of miRNAs in the pig at gestational Day 10 after daily estradiol-17β (E2) application starting at fertilization using either 0, 0.05 (ADI-acceptable daily intake), 10 (NOEL-no-observed-effect level) and 1,000 (high dose) µg E2/kg body weight/day, respectively. In endometrial homogenates, E2 (p < 0.001) and total estrogen concentrations (p < 0.001) were significantly increased, namely 28- and 160-fold, respectively, in the high dose group as compared to the control. Additionally, total estrogens were sixfold elevated in the NOEL group. Interestingly, high-throughput sequencing of small non-coding RNA libraries did not indicate any differentially expressed miRNAs between the treatment groups and the control group. The expression of 12 potential E2 target miRNAs investigated by RT-qPCR were equally unaffected. Thus, preimplantational E2 exposure resulted in significantly higher endometrial estrogen concentrations, but did not perturb the expression profile of endometrial miRNAs.

Abstract

Porcine conceptuses synthesize estrogens between Day 11 and 12 as signal for maternal recognition of pregnancy. A preimplantational estrogen exposure to pregnant gilts has been associated with embryonic losses and changes in endometrial mRNA expression. MicroRNAs (miRNAs) play a key role in the mRNA regulation by modulating the expression. Effects of estrogens on endometrial miRNAs have not been investigated in this context so far. Thus, we studied the endometrial expression profile of miRNAs in the pig at gestational Day 10 after daily estradiol-17β (E2) application starting at fertilization using either 0, 0.05 (ADI-acceptable daily intake), 10 (NOEL-no-observed-effect level) and 1,000 (high dose) µg E2/kg body weight/day, respectively. In endometrial homogenates, E2 (p < 0.001) and total estrogen concentrations (p < 0.001) were significantly increased, namely 28- and 160-fold, respectively, in the high dose group as compared to the control. Additionally, total estrogens were sixfold elevated in the NOEL group. Interestingly, high-throughput sequencing of small non-coding RNA libraries did not indicate any differentially expressed miRNAs between the treatment groups and the control group. The expression of 12 potential E2 target miRNAs investigated by RT-qPCR were equally unaffected. Thus, preimplantational E2 exposure resulted in significantly higher endometrial estrogen concentrations, but did not perturb the expression profile of endometrial miRNAs.

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Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Veterinary Clinic > Department of Farm Animals
Dewey Decimal Classification:570 Life sciences; biology
630 Agriculture
Scopus Subject Areas:Life Sciences > Genetics
Life Sciences > Developmental Biology
Life Sciences > Cell Biology
Uncontrolled Keywords:Developmental Biology, Genetics, Cell Biology
Language:English
Date:9 March 2018
Deposited On:22 Aug 2018 15:03
Last Modified:29 Jul 2020 07:33
Publisher:Wiley-Blackwell Publishing, Inc.
ISSN:1040-452X
Additional Information:This is the peer reviewed version of the following article: Flöter VL, Lorenz A‐K, Kirchner B, Pfaffl MW, Bauersachs S, Ulbrich SE. Impact of preimplantational oral low‐dose estradiol‐17β exposure on the endometrium: The role of miRNA. Mol Reprod Dev. 2018;85:417–426, which has been published in final form at https://doi.org/10.1002/mrd.22975. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving (http://olabout.wiley.com/WileyCDA/Section/id-820227.html#terms).
OA Status:Green
Publisher DOI:https://doi.org/10.1002/mrd.22975
PubMed ID:29542831

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