The adverse effects of vitrification on mouse embryo development and metabolic phenotype in offspring

Author:

Chen Qiaoyu123,Zhou Dan1ORCID,Wang Changxin4,Ye Mingming1,Jia Yanping1,Liu Binya1,Bukulmez Orhan5,Norman Robert J.6,Hu Hanxin7,Yeung Shu‐Biu8,Teng Xiaoming1,Liu Wenqiang1,Chen Miaoxin1ORCID

Affiliation:

1. Centre for Assisted Reproduction, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal‐Fetal Medicine and Gynecologic Oncology Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University Shanghai China

2. Department of Anatomy and Developmental Biology Monash University Clayton Victoria Australia

3. Development and Stem Cells Program Monash Biomedicine Discovery Institute Clayton Victoria Australia

4. Department of Pathology The Second Affiliated Hospital, Zhejiang University School of Medicine Hangzhou China

5. Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology The University of Texas Southwestern Medical Center Dallas Texas USA

6. Robinson Research Institute, School of Paediatrics and Reproductive Health The University of Adelaide Adelaide South Australia Australia

7. School of Life Sciences and Technology Tongji University Shanghai China

8. Shenzhen Key Laboratory of Fertility Regulation, Center of Assisted Reproduction and Embryology the University of Hong Kong – Shenzhen Hospital Shenzhen China

Abstract

AbstractEmbryo vitrification is a standard procedure in assisted reproductive technology. Previous studies have shown that frozen embryo transfer is associated with an elevated risk of adverse maternal and neonatal outcomes. This study aimed to explore the effects of mouse blastocyst vitrification on the phenotype of vitrified‐warmed blastocysts, their intrauterine and postnatal development, and the long‐term metabolic health of the derived offspring. The vitrified‐warmed blastocysts (IVF + VT group) exhibited reduced mitochondrial activity, increased apoptotic levels, and decreased cell numbers when compared to the fresh blastocysts (IVF group). Implantation rates, live pup rates, and crown‐rump length at E18.5 were not different between the two groups. However, there was a significant decrease in fetal weight and fetal/placental weight ratio in the IVF + VT group. Furthermore, the offspring of the IVF + VT group at an age of 36 weeks had reduced whole energy consumption, impaired glucose and lipid metabolism when compared with the IVF group. Notably, RNA‐seq results unveiled disturbed hepatic gene expression in the offspring from vitrified‐warmed blastocysts. This study revealed the short‐term negative impacts of vitrification on embryo and fetal development and the long‐term influence on glucose and lipid metabolism that persist from the prenatal stage into adulthood in mice.

Funder

National Natural Science Foundation of China

Shanghai Municipal Health Bureau

Science and Technology Commission of Shanghai Municipality

Publisher

Wiley

Subject

Genetics,Molecular Biology,Biochemistry,Biotechnology

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