Mitochondrial oxygen consumption rate of human embryos declines with maternal age

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EMBRYO BIOLOGY

Mitochondrial oxygen consumption rate of human embryos declines with maternal age Naoharu Morimoto 1,2,3 & Shu Hashimoto 2 & Masaya Yamanaka 1 & Tatsuya Nakano 1 & Manabu Satoh 1 & Yoshiharu Nakaoka 1 & Hisataka Iwata 4 & Atsushi Fukui 3 & Yoshiharu Morimoto 5 & Hiroaki Shibahara 3 Received: 12 February 2020 / Accepted: 23 June 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract Purpose The fertility of women decreases with age because of factors such as an increased incidence of aneuploidies and— possibly—decreased mitochondrial activity in oocytes. However, the relationship between maternal aging and mitochondrial function of their embryos remains unknown. Here, we assessed the relationship between maternal age and mitochondrial functions in their oocytes and embryos Methods The relationships between maternal age and oxygen consumption rates (OCRs), mitochondrial DNA (mtDNA) copy numbers, or blastocyst development was investigated using 81 embryos donated from 63 infertility couples. The developmental rates from morulae to blastocysts were retrospectively analyzed using data of 105 patients. Results The OCRs of morulae decreased with maternal age (r2 = 0.48, P < 0.05) although there were no relationships between maternal age and mtDNA copy number in any stages. The more oxygen consumed at the morula stage, the shorter time was required for embryo development to the mid-stage blastocyst (r2 = 0.236, P < 0.05). According to the clinical data analysis, the developmental rate from morulae to blastocysts decreased with maternal age (P < 0.05, < 37 years, 81.1%, vs. ≥ 37 years, 64.1%). Conclusions The data of the present study revealed that mitochondrial function at the morula stage of human embryos decreased with their maternal age and a decrease of mitochondrial function led to slow-paced development and impaired developmental rate from morulae to blastocysts. Keywords Maternal age . Mitochondrial function . Oxygen consumption rate

Introduction The fertility of women decreases with age [1]. One of the main reasons for the poor development of embryos obtained from Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10815-020-01869-5) contains supplementary material, which is available to authorized users. * Shu Hashimoto [email protected] 1

IVF Namba Clinic, Osaka 550-0015, Japan

2

Reproductive Science, Graduate School of Medicine, Osaka City University, Osaka 545-8585, Japan

3

Department of Obstetrics and Gynecology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan

4

Department of Animal Science, Tokyo University of Agriculture, Kanagawa 243-0034, Japan

5

HORAC Grand Front Osaka Clinic, Osaka 530-0011, Japan

older women is an increased rate of chromosomal aberrations [2] caused by premature bivalent separation into univalents during meiosis [3]. Additionally, a decline in mitochondrial function in oocytes with advancing age has also been proposed as a reason for poor embryo developmental competence