The number of children born after assisted reproductive technology (ART) is accumulating rapidly, and the health problems of the children are extensively concerned. This study aims to evaluate whether ART procedures alter behaviours in male offspring. Mouse models were utilized to establish three groups of offspring conceived by natural conception (NC), in vitro fertilization and embryo transfer (IVF-ET), and frozen-thawed embryo transfer (IVF-FET), respectively. A battery of behaviour experiments for evaluating anxiety and depression levels, including the open field test (OFT), elevated plus maze (EPM) test, light/dark transition test (L/DTT), tail suspension test (TST), forced swimming test (FST), and sucrose preference test (SPT) was carried out. Aged (18 months old), but not young (3 months old), male offspring in the IVF-ET and IVF-FET groups, compared with those in the NC group, exhibited increased anxiety and depression-like behaviours. The protein expression levels of three neurotrophins in PFC or hippocampus in aged male offspring from the IVF-ET and IVF-FET groups reduced at different extent, in comparison to NC group. RNA sequencing (RNA-Seq) was performed in the hippocampus of 18 months old offspring to further explore the gene expression profile changes in the three groups. KEGG analyses revealed the coexisted pathways, such as PI3K-Akt signalling pathway, which potentially reflected the similarity and divergence in anxiety and depression between the offspring conceived by IVF-ET and IVF-FET. Our research suggested the adverse effects of advanced age on the psychological health of children born after ART should be highlighted in the future.
Ning-Xin Qin, Yi-Ran Zhao, Wei-Hui Shi, Zhi-Yang Zhou, Ke-Xin Zou, Chuan-Jin Yu, Xia Liu, Ze-Han Dong, Yi-Ting Mao, Cheng-Liang Zhou, Jia-Le Yu, Xin-Mei Liu, Jian-Zhong Sheng, Guo-Lian Ding, Wen-Long Zhao, Yan-Ting Wu, and He-Feng Huang
Xue-Ying Zhang, Yi-Meng Xiong, Ya-Jing Tan, Li Wang, Rong Li, Yong Zhang, Xin-Mei Liu, Xian-Hua Lin, Li Jin, Yu-Ting Hu, Zhen-Hua Tang, Zheng-Mu Wu, Feng-Hua Yin, Zheng-Quan Wang, Ye Xiao, Jian-Zhong Sheng, and He-Feng Huang
Fertilization failure often occurs during in vitro fertilization (IVF) cycles despite apparently normal sperm and oocytes. Accumulating evidence suggests that mitochondria play crucial roles in the regulation of sperm function and male fertility. 3-Nitrophthalic acid (3-NPA) can induce oxidative stress in mitochondria, and melatonin, as an antioxidant, can improve mitochondrial function by reducing mitochondrial oxidative stress. The role of sperm mitochondrial dysfunction in fertilization failure during IVF is unclear. The present study revealed that spermatozoa with low, or poor, fertilization rates had swollen mitochondria, increased mitochondria-derived ROS, and attenuated mitochondrial respiratory capacity. 3-NPA treatment enhanced mitochondrial dysfunction in sperm. Spermatozoa with poor fertilization rates, and spermatozoa treated with 3-NPA, had reduced penetration ability. The concentration of melatonin was decreased in semen samples with low and poor fertilization rates. Melatonin, not only decreased excessive mitochondria-derived ROS, but also ‘rescued’ the reduced penetration capacity of spermatozoa treated with 3-NPA. Taken together, the study suggested that mitochondria-derived ROS and mitochondrial respiratory capacity are independent bio-markers for sperm dysfunction, and melatonin may be useful in improving sperm quality and overall male fertility.