| Title: | PMCA1 depletion in mouse eggs amplifies calcium signaling and impacts offspring growthdagger |
| Author(s): | Savy V; Stein P; Shi M; Williams CJ; |
| Address: | "Reproductive & Developmental Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA. Biostatistics & Computational Biology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA" |
| ISSN/ISBN: | 1529-7268 (Electronic) 0006-3363 (Print) 0006-3363 (Linking) |
| Abstract: | "Egg activation in mammals is triggered by oscillations in egg intracellular calcium (Ca2+) level. Ca2+ oscillation patterns can be modified in vitro by changing the ionic composition of culture media or in vivo by conditions affecting mitochondrial function, such as obesity and inflammation. In mice, disruption of Ca2+ oscillations in vitro impacts embryo development and offspring growth. Here we tested the hypothesis that, even without in vitro manipulation, abnormal Ca2+ signaling following fertilization impacts offspring growth. Plasma membrane Ca2+ ATPases (PMCA) extrude cytosolic Ca2+ to restore Ca2+ homeostasis. To disrupt Ca2+ signaling in vivo, we conditionally deleted PMCA1 (cKO) in oocytes. As anticipated, in vitro fertilized cKO eggs had increased Ca2+ exposure relative to controls. To assess the impact on offspring growth, cKO females were mated to wild type males to generate pups that had high Ca2+ exposure at fertilization. Because these offspring would be heterozygous, we also tested the impact of global PMCA1 heterozygosity on offspring growth. Control heterozygous pups that had normal Ca2+ at fertilization were generated by mating wild type females to heterozygous males; these control offspring weighed significantly less than their wild type siblings. However, heterozygous offspring from cKO eggs (and high Ca2+ exposure) were larger than heterozygous controls at 12 week-of-age and males had altered body composition. Our results show that global PMCA1 haploinsufficiency impacts growth and support that abnormal Ca2+ signaling after fertilization in vivo has a long-term impact on offspring weight. These findings are relevant for environmental and medical conditions affecting Ca2+ handling and for design of culture conditions and procedures for domestic animal and human assisted reproduction" |
| Keywords: | Male Female Mice Humans Animals *Calcium Signaling/physiology *Calcium/metabolism Fertilization/physiology Zygote/metabolism Oocytes/metabolism Mammals/metabolism DOHaD Pmca1 calcium egg activation fertilization; |
| Notes: | "MedlineSavy, Virginia Stein, Paula Shi, Min Williams, Carmen J eng ZIA ES102985/ImNIH/Intramural NIH HHS/ 2022/09/22 Biol Reprod. 2022 Dec 10; 107(6):1439-1451. doi: 10.1093/biolre/ioac180" |
