OR08-5 The Effect of Short-Term Western-Style Diet Consumption on Primate Ovarian Follicle, Oocyte, and Embryo Development

Abstract

A maternal high-fat diet is associated with reduced oocyte quality, fertilization, as well as altered preimplantation embryo development. It is unclear, especially in women, if these effects are due to the diet itself or the subsequent development of metabolic dysfunction. Thus, a longitudinal study was performed using the clinically relevant rhesus macaque model to test the hypothesis that short-term exposure to a high-fat Western Style Diet (WSD) negatively impacts primate ovarian follicle, oocyte, and preimplantation embryo development. Oocytes were collected from regularly cycling female rhesus macaques (N=10; ages 5-6yrs) after undergoing a controlled ovarian stimulation protocol (COS1) while consuming a Standard Chow Diet (SCD; 13% fat). Animals were then switched to WSD (35% fat) for 6-8 months prior to going through a second COS protocol (COS2). Follicular fluid (FF) was collected from 4 individual follicles per female per COS and pooled for subsequent steroid and cytokine analysis by mass spectrometry and a multiplex assay system (Luminex), respectively. Individually isolated oocytes and oocytes aspirated from the remaining follicles were then assessed for reinitiation of meiosis, in vitro fertilization (IVF) and subsequent blastocyst formation rates. Time-lapse monitoring (TLM) was performed post-IVF to study initial mitotic division kinetics, as well as cellular fragmentation and multipolar divisions. Weight gain by the female macaques post-WSD intake recorded at COS2 was significant (P=0.0001), but insulin resistance (HOMA-IR) at the time of COS2 was not significantly different from COS1. Of the 10 females, 2 were resistant to weight gain and another 2 did not respond to COS2. Excluding the 2 non-responsive females, FF interleukin (IL)-1 receptor antagonist (IL-1RA; P=0.009) and IL-2 (P=0.004) levels decreased post-WSD intake. The levels of cortisone, an inactive metabolite of the biologically active glucocorticoid cortisol, were 18% higher, while mean cortisol levels were 22% lower, in the FF collected from COS2 relative to COS1. This resulted in a reduced cortisol:cortisone ratio post-WSD intake (P=0.028) and negatively correlated with the resident oocyte’s ability to form a blastocyst following IVF (R=-0.66; P<0.05). While 138 blastocysts were obtained from COS1, the total number blastocysts collected from COS significantly decreased to 77 (P=0.036) post-WSD intake (COS2). Lastly, a higher occurrence of multipolar divisions was observed with fertilized oocytes collected post-WSD diet consumption (COS2) compared to fertilized oocytes collected from animals receiving SCD (COS1). These results demonstrate that WSD consumption alters the intrafollicular microenvironment as well as oocyte and preimplantation embryo development in non-human primates even in the absence of large-scale metabolic changes. Funding: NIH P51 OD011092, NCTRI P50 HD071836