Transcriptome profiles of blastocysts originating from oocytes matured in follicular fluid from preovulatory follicles of greater or lesser maturity.

Abstract

Background: Oocyte competence for early embryo development relies on intercellular communication between the maturing oocyte and preovulatory follicle. Preovulatory follicle maturity, as indicated by serum estradiol concentration or follicle diameter, has previously been linked to pregnancy, follicular fluid metabolites, cumulus-oocyte metabolism, and oocyte competency for embryo development. Such relationships indicate metabolic and developmental programming of the oocyte based on the preovulatory follicle's physiological status, but downstream impacts on the molecular signature of blastocysts have not been examined. We hypothesized that supplementing maturing oocytes with follicular fluid originating from preovulatory follicles of greater or lesser maturity would impact the transcriptome of resulting blastocysts and indicate metabolic programming of the embryo that originated from the oocyte's maturation environment. The objective was to investigate the effect of follicle maturity on the oocyte by examining the transcriptome of blastocysts originating from oocytes matured in the presence of follicular fluid from preovulatory follicles of greater or lesser maturity.

Results: In vitro maturing oocytes were supplemented with follicular fluid collected from preovulatory follicles of greater or lesser maturity. Following identical embryo culture procedures, RNA-sequencing was performed on pools of 2 blastocysts (Greater, n = 12; Lesser, n = 15; all with stage code = 7 and quality code = 1). A total of 12,310 genes were identified in blastocysts after filtering to remove lowly abundant genes. There were 113 genes that differed in expression between blastocysts originating from oocytes matured in greater versus lesser maturity follicular fluid (eFDR < 0.01). Although no pathways were significantly enriched with differentially expressed genes, transcriptome profiles suggested improved Wnt/β-catenin signaling, metabolism, and protection from oxidative stress in blastocysts derived from oocytes matured in greater maturity follicular fluid, while potential unregulated cell growth presented in blastocysts resulting from the lesser follicle maturity treatment.

Conclusions: Follicular fluid from preovulatory follicles of greater physiological maturity may better prepare maturing oocytes for early embryo development. Furthermore, oocytes matured in follicular fluid from preovulatory follicles of lesser maturity may attempt to overcompensate for nutrient deficit during oocyte maturation, leading to uncontrolled cellular growth and increased oxidative stress.