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1 October 2002 Developmental Changes in the Management of Acid Loads During Preimplantation Mouse Development
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Intracellular pH recovery in Quackenbush Swiss mouse preimplantation embryos following acid loading was investigated under conditions of H -monocarboxylate cotransporter inactivity. Isoform-sensitive inhibitors of Na -H exchange (NHE) were used to block the Na -dependent component of the response. A biphasic dose-response curve for HOE-694 and N-methylisopropylamiloride (MIA) suggested that two isoforms (putatively NHE1 and NHE3) are active in the oocyte, 1-cell, and 2-cell stages. By the blastocyst stage, loss of one of the MIA-sensitive NHE activities (putatively NHE3) was observed in isolated inner cell masses, and an MIA-resistant component of the recovery was identified. The MIA-resistant component was inhibited by 2 mM amiloride and enhanced by external K and by 4,4′-diisothiocyanostilbene-2,2′-disulfonate, suggesting NHE4 activity. However, unlike NHE4 in other tissues, the MIA-resistant component did not transport Li in exchange for H , and reverse transcription-polymerase chain reaction detected NHE4 mRNA in the oocyte but not in later stages. Trophoblast, whether in intact or collapsed blastocysts, did not show measurable NHE activity or MIA-sensitive activity during recovery from acid load. Both trophoblast and pluriblast manifested an H conductance in response to acid load. This H conductance was first detected at the 8-cell stage and was blocked by zinc in the isolated inner cell mass but not in trophoblast. No other effective inhibitors of its activity were found.

E. A. Harding, C. A. Gibb, M. H. Johnson, D. I. Cook, and M. L. Day "Developmental Changes in the Management of Acid Loads During Preimplantation Mouse Development," Biology of Reproduction 67(5), 1419-1429, (1 October 2002).
Received: 19 March 2002; Accepted: 1 June 2002; Published: 1 October 2002

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