Nuclear Receptors in Ovarian Function.

The ovary undergoes cycles of hormone production that regulate physiological changes necessary for folliculogenesis, ovulation and luteinisation, ultimately contributing to female reproductive success. Crucial to these biological processes is stage-specific nuclear receptor signalling. While the transcriptional regulatory roles of steroid receptors in female fertility and especially ovarian functions have long been documented, non-steroid receptors also play an important part in regulating gene expression at various stages of ovarian development. The recent application of high-throughput genomic and transcriptomic technologies has begun to shed light on the molecular mechanisms underlying ovarian nuclear receptor actions and pointed to a complex interplay between highly specific transcription co-regulators as well as between nuclear receptors in mediating mutual as well as unique target genes. Interrelationships between nuclear receptors as well as the involvement of context-specific protein and non-protein co-regulators are likely keys to the precise and specific nuclear receptor action in the ovary. Leveraging such knowledge on the nuclear receptor network is especially valuable in the development of novel fertility treatments as well as female contraceptives.

Human cumulus cell gene expression as a biomarker of pregnancy outcome after single embryo transfer.

OBJECTIVE: To identify the cumulus cell gene expression associated with oocyte developmental competence, specifically live birth, after single ET (SET) assisted reproductive technology. DESIGN: Retrospective gene expression analysis in human cumulus cells from oocytes that established a pregnancy resulting in live birth versus no pregnancy after SET. SETTING: Independent IVF clinic and research institute. PATIENT(S): Women undergoing IVF/intracytoplasmic sperm injection with SET. INTERVENTION(S): Quantitative reverse-transcriptase-polymerase chain reaction analysis was performed on cumulus masses collected before insemination. Oocytes and embryos were cultured and transferred independently in 38 patients undergoing elective SET. Paired cumulus samples from oocytes that developed into high- versus low-grade embryos also were compared. MAIN OUTCOME MEASURE(S): Gene expression profiles of metabolic (ALDOA, LDHA, PFKP, PKM2), signaling (AHR, GREM1, PTGS2, STS), extracellular matrix (HAS2, PTX3, TNFAIP6, VCAN), and loading control GAPDH in individual cumulus masses. RESULT(S): VCAN and PTGS2 mRNA expression was significantly higher in cumulus cells from oocytes yielding a pregnancy resulting in a live birth, while PTX3 mRNA expression trended toward higher expression in pregnant samples. Cumulus cell levels of VCAN, GREM1, and PFKP correlated with birth weight in patients at 38 weeks of gestation. No genes correlated with clinical embryo morphology scores. CONCLUSION(S): Cumulus cell VCAN, PTGS2, GREM1, and PFKP expression may identify oocytes with high developmental potential, leading to enhanced implantation rates and greater developmental capacity throughout gestation.