Abstract
The maturation of the oocyte is influenced by cumulus cells (CCs) and associated with pregnancy rate, whereas the influencing factors have not been completely elucidated in the CCs. In this study, we identified new regulators of CCs for high-quality oocytes and successful pregnancies during assisted reproductive techniques. CCs were collected from cumulus–oocyte complexes (COCs) in young (≤33 years old) and old (≥40 years old) women undergoing intracytoplasmic sperm injection (ICSI) procedures. We screened for factors differentially expressed between young vs. old CCs and pregnancy vs. non-pregnancy using whole mRNA-seq-next-generation sequencing (NGS). We characterized the transcriptome of the CCs to identify factors critical for achieving pregnancy in IVF cycles. Women in the young and old pregnancy groups exhibited the up- and downregulation of multiple genes compared with the non-pregnancy groups, revealing the differential regulation of several specific genes involved in ovarian steroidogenesis in CCs. It was shown that the low-density lipoprotein (LDL) receptor to the steroidogenesis pathway was upregulated in CCs with higher maturity rates of oocytes in the pregnancy group. In conclusion, a higher pregnancy rate is related to the signaling pathway of steroidogenesis by the LDL receptor in infertile women undergoing IVF procedures.
Highlights
In assisted reproductive technology (ART), age is a major determinant of successful pregnancy outcomes [1,2,3]
All in vitro fertilization (IVF) patients were stimulated using Gonadotropin-releasing hormone (GnRH) antagonist protocols with no significant difference in the doses of gonadotropin administered
We identified a specific transcriptome profile in the Cumulus cells (CCs) of young and old IVF women
Summary
In assisted reproductive technology (ART), age is a major determinant of successful pregnancy outcomes [1,2,3]. No curative treatment is available for infertility related to advanced age, which manifests as a reduced competence of oocytes and embryos in ART [1]. Among women of advanced age undergoing in vitro fertilization (IVF), those with a history of successful live births may have different GC and CC responses during follicular development from those who have experienced failed pregnancies [11]. Oocytes from women over 40 years old have reduced developmental competence. No critical factors have been identified that can mitigate the risk of not achieving pregnancy at advanced maternal age
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