Qing Zhou:
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Infertility is a critical component of reproductive health and remains a highly
prevalent global condition. In many cases, couples with infertility may choose assisted
reproductive technology (ART) to increase their chances of conception. However, an
increasing application of ART treatment worldwide has also generated both scientific
and public interest in its efficacy and safety. Since successful development of embryos
in vitro is one of the key steps in ART and has a crucial influence on pregnancy outcome,
an improved understanding of these processes will help us figure out the underlying
mechanisms in ART failure due to poor embryonic development, especially for couples
without normal embryos for transfer in several cycles.
In this thesis, I discuss maternal and paternal contribution to the development of
human preimplantation embryos. Firstly, I give a brief introduction to the present
clinical status of infertility and great concerns in the field of ART. Secondly, I
systematically introduce the developmental process of human preimplantation embryos,
including maturation of gametes, the process of fertilization, the dynamic
reprogramming of epigenome upon fertilization, the transcriptional activation of
embryonic genome, and the lineage differentiation of embryos at the blastocyst stage.
Lastly, I summarize the clinical situation and scientific findings of couples suffering
from recurrent ART failure due to poor embryonic development.
Next, I present our findings on the maternal and paternal contribution to human
embryogenesis based on the dynamics of parental-of-origin sex chromosomes, as well
as the effects of parental genetic background on embryonic development. The distinct
activation and silencing of sex chromosomes result in an imbalanced dosage of gene
expression, and thus, have potential effects on the sex-specific behaviour of early
embryos. The analysis of couples with recurrent poor embryonic development indicate
that they are highly heterogeneous both phenotypically and genetically. These results
will further knowledge within the ART field and possibly improve the treatment of
infertility. Our findings also enable potential application of whole genome sequencing
to clinical diagnosis and it could contribute to improve genetic counselling of couples with a history of ART failure. Hence, all the results will possibly expand the capabilities
of ART and enhance reproductive health.