Stage-Specific L-Proline Uptake by Amino Acid Transporter Slc6a19/B0AT1 Is Required for Optimal Preimplantation Embryo Development in Mice

Stage-Specific L-Proline Uptake by Amino Acid Transporter Slc6a19/B0AT1 Is Required for Optimal Preimplantation Embryo Development in Mice.

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.3390/cells12010018
Journal or Publication Title: Cells
Volume: 12
Number: 1
Page Range: p. 18
Date: 21 December 2022
Divisions: Cancer and Gene Regulation
Gene and Stem Cell Therapy
Depositing User: General Admin
Identification Number: 10.3390/cells12010018
ISSN: 2073-4409
Date Deposited: 15 Mar 2023 23:41
Abstract:

L-proline (Pro) has previously been shown to support normal development of mouse embryos. Recently we have shown that Pro improves subsequent embryo development when added to fertilisation medium during in vitro fertilisation of mouse oocytes. The mechanisms by which Pro improves embryo development are still being elucidated but likely involve signalling pathways that have been observed in Pro-mediated differentiation of mouse embryonic stem cells. In this study, we show that B0AT1, a neutral amino acid transporter that accepts Pro, is expressed in mouse preimplantation embryos, along with the accessory protein ACE2. B0AT1 knockout (Slc6a19−/−) mice have decreased fertility, in terms of litter size and preimplantation embryo development in vitro. In embryos from wild-type (WT) mice, excess unlabelled Pro inhibited radiolabelled Pro uptake in oocytes and 4–8-cell stage embryos. Radiolabelled Pro uptake was reduced in 4–8-cell stage embryos, but not in oocytes, from Slc6a19−/− mice compared to those from WT mice. Other B0AT1 substrates, such as alanine and leucine, reduced uptake of Pro in WT but not in B0AT1 knockout embryos. Addition of Pro to culture medium improved embryo development. In WT embryos, Pro increased development to the cavitation stage (on day 4); whereas in B0AT1 knockout embryos Pro improved development to the 5–8-cell (day 3) and blastocyst stages (day 6) but not at cavitation (day 4), suggesting B0AT1 is the main contributor to Pro uptake on day 4 of development. Our results highlight transporter redundancy in the preimplantation embryo.
Keywords: proline; amino acid transporter; Slc6a19; B0AT1; preimplantation embryo; mouse

Creators:
Creators
Email
Treleaven, Tamara
UNSPECIFIED
Zada, Matthew
UNSPECIFIED
Nagarajah, Rajini
UNSPECIFIED
Bailey, Charles G.
UNSPECIFIED
Rasko, John E. J.
UNSPECIFIED
Morris, Michael B.
UNSPECIFIED
Day, Margot L.
UNSPECIFIED
Last Modified: 15 Mar 2023 23:41
URI: https://eprints.centenary.org.au/id/eprint/1434

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