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Persistence and intergenerational transmission of differentially expressed genes in the testes of intracytoplasmic sperm injection conceived mice

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Abstract

Intracytoplasmic sperm injection (ICSI) is commonly used to solve male infertility problems. Previous studies showed that early environmental exposure of an embryo may influence postnatal development. To detect whether ICSI operations affect the reproductive health of a male or his offspring, we established assisted reproductive technologies (ART) conceived mouse models, and analyzed gene expression profiles in the testes of both ICSI and naturally conceived (NC) newborn F1 mice using micro-array analysis. Among the differentially expressed genes, we focused on the expression of eight male reproduction-related genes. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) was used to analyze the expression of these genes in the testes of both adult and old F1 generation mice and adult F2 generation mice. Our results showed that down-regulated and somatic cell-expressed genes in newborn mice retained their differential expression patterns in adult and old F1 generation individuals, implying the persistence and fetal origin of the alteration in the expression of these genes. The intergenerational transmission of differential gene expression was observed, but most changes tended to be reduced in adult F2 generations. Controlled ovarian hyperstimulation (COH) and in vitro fertilization (IVF) mice models were added to explore the precise factors contributing to the differences in ICSI offspring. The data demonstrated that superovulation, in vitro culture, and mechanical stimulation involved in ICSI had a cumulative effect on the differential expression of these male reproductive genes.

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Authors and Affiliations

  1. Key Laboratory of Reproductive Genetics (Zhejiang), Ministry of Education, and Centre of Reproductive Medicine, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, China

    Li-ya Wang, Ning Wang, Fang Le, Le-jun Li, Xiao-zhen Liu, Ying-ming Zheng, Hang-ying Lou, Xiang-rong Xu, Xiao-ming Zhu, Yi-min Zhu, He-feng Huang & Fan Jin

  2. Department of Gynecologic Oncology, Henan Cancer Hospital, Zhengzhou, 450003, China

    Lei Li

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  1. Li-ya Wang
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  2. Ning Wang
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  3. Fang Le
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  4. Lei Li
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  5. Le-jun Li
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  6. Xiao-zhen Liu
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  7. Ying-ming Zheng
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  8. Hang-ying Lou
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  12. He-feng Huang
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  13. Fan Jin
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Correspondence to Fan Jin.

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The two authors contributed equally to this work

Project supported by the National Basic Research Program (973) of China (Nos. 2007CB948104 and 2012CB944901), the National Natural Science Foundation of China (Nos. 81070532, 81070541, and 81200475), and the Zhejiang Provincial Natural Science Foundation of China (Nos. Y2090084, Y2100397, and Y2100199)

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Wang, Ly., Wang, N., Le, F. et al. Persistence and intergenerational transmission of differentially expressed genes in the testes of intracytoplasmic sperm injection conceived mice. J. Zhejiang Univ. Sci. B 14, 372–381 (2013). https://doi.org/10.1631/jzus.B1200321

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  • DOI: https://doi.org/10.1631/jzus.B1200321

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