Reproductive Outcomes from Maternal Loss of Nlrp2 Are Not Improved by IVF or Embryo Transfer Consistent with Oocyte-Spec
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REPRODUCTIVE BIOLOGY: ORIGINAL ARTICLE
Reproductive Outcomes from Maternal Loss of Nlrp2 Are Not Improved by IVF or Embryo Transfer Consistent with Oocyte-Specific Defect Sara Arian 1 & Jessica Rubin 1,2 & Imen Chakchouk 1 & Momal Sharif 1 & Sangeetha K. Mahadevan 1 & Hadi Erfani 1 & Katharine Shelly 3 & Lan Liao 4 & Isabel Lorenzo 3 & Rajesh Ramakrishnan 1,5 & Ignatia B. Van den Veyver 1,3,6 Received: 17 June 2020 / Accepted: 11 October 2020 # Society for Reproductive Investigation 2020
Abstract Nlrp2 encodes a protein of the oocyte subcortical maternal complex (SCMC), required for embryo development. We previously showed that loss of maternal Nlrp2 in mice causes subfertility, smaller litters with birth defects, and growth abnormalities in offspring, indicating that Nlrp2 is a maternal effect gene and that all embryos from Nlrp2-deficient females that were cultured in vitro arrested before the blastocysts stage. Here, we used time-lapse microscopy to examine the development of cultured embryos from superovulated Nlrp2-deficient and wild-type mice after in vivo and in vitro fertilization. Embryos from Nlrp2deficient females had similar abnormal cleavage and fragmentation and arrested by blastocyst stage, irrespective of fertilization mode. This indicates that in vitro fertilization does not further perturb or improve the development of cultured embryos. We also transferred embryos from superovulated Nlrp2-deficient and wild-type females to wild-type recipients to investigate if the abnormal reproductive outcomes of Nlrp2-deficient females are primarily driven by oocyte dysfunction or if a suboptimal intra-uterine milieu is a necessary factor. Pregnancies with transferred embryos from Nlrp2-deficient females produced smaller litters, stillbirths, and offspring with birth defects and growth abnormalities. This indicates that the reproductive phenotype is oocyte-specific and is not rescued by development in a wild-type uterus. We further found abnormal DNA methylation at two maternally imprinted loci in the kidney of surviving young adult offspring, confirming persistent DNA methylation disturbances
Sara Arian and Jessica Rubin contributed equally to this work. Summary Sentence Female mice with loss of Nlrp2 have poor reproductive outcomes that are not rescued by in vitro fertilization or transfer of embryos to the uterus of a wild-type female, supporting that this maternal effect mutation causes an oocyte-specific defect. Conference presentation: This work was presented in part at the annual meeting of the Society for Reproductive Investigation (SRI), March 2019, Paris, France, and at the Texas Forum of Reproductive Science (TFRS), April 2017, Houston, Texas. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s43032-020-00360-x) contains supplementary material, which is available to authorized users. * Ignatia B. Van den Veyver [email protected]
4
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, USA
1
Department of Obstetrics and Gynec
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