O-155 Dietary caloric normalization or restriction as preconception care strategies: impact on oocyte developmental competence and quality in high fat/high sugar-induced obese outbred mice
Authors: Smits A , Pintelon I , Thys S , Bols P E J , Marei W F A , Leroy J L M R 
Published: August 2021

Abstract

Study question
Can diet normalization or caloric restriction (CR) for two weeks be used as a preconception care intervention in obese Swiss mice to restore oocyte development and quality

Summary answer
Diet normalization or CR as short-term preconception care interventions in obese mice only partially restored oocyte quality but did improve overall developmental competence.

What is known already
Maternal metabolic disorders like obesity and metabolic syndrome may result in decreased oocyte and embryo quality, and thus reproductive failure. Overweight and obese patients are advised to lose weight before conception to increase the chance of a healthy pregnancy. However, as human studies show no univocal guidelines, more fundamental research might provide additional answers. In order to avoid interference with increased maternal age, the question remains if oocyte quality can be restored after only a short preconception care intervention (PCCI).

Study design, size, duration
Outbred mice were fed a control (CTRL) or high-fat/high-sugar (HF) diet for seven weeks. Afterwards, HF-mice were put on different PCCIs for two weeks, resulting in four treatment groups: control diet (9w; CTRL_CTRL), HF diet (9w; HF_HF), switch from HF (7w) to an ad libitum control diet for 2w (HF_CTRL) or to a 30% CR diet for 2w (HF_CR). Oocyte developmental competence (n = 357) and quality (12-16 oocytes /treatment, scored blinded) were determined, using 6-8 mice/treatment.

Participants/materials, setting, methods
Body weight changes were recorded. In vivo matured oocytes were collected after superovulation and analysed for quality or in vitro fertilized and cultured. Oocyte quality was determined by staining for lipid content (Bodipy) and mitochondrial inner membrane potential and active mitochondria localization (JC-1). Oocyte developmental competence [cleavage (24h p.i.) and blastocyst rates (5 days p.i.)] was scored. Categorical and numerical data were analysed using binary logistic regression and ANOVA, respectively and corrected for multiple testing.

Main results and the role of chance
Compared to the CTRL group, HF diet increased body weight after 7 weeks by 24.19% (P &lt; 0.001). After the start of the PCCI, both HF_CTRL and HF_CR mice progressively lost weight and reached values similar to control mice after two weeks. HF_HF diet increased the intracellular lipid content in oocytes with 54.3% compared to the CTRL_CTRL group (P &lt; 0.05). This increased content was (partially) normalized in both preconception care intervention groups, even similar to the control levels in the HF_CTRL group. Both HF_HF and HF_CR oocytes showed a tendency to an increased ratio of active/total mitochondria when compared to the CTRL_CTRL group (P = 0.081, P = 0.083 respectively). In addition, active oocyte mitochondria in the HF_HF group were less pericortically distributed compared to controls. This was also the case in both preconception care intervention groups (P &lt; 0.05). After two weeks of PCCI, oocytes from HF_HF mice displayed lower cleavage rates than those from CTRL_CTRL mice (36.26% vs. 64.52%, P &lt; 0.05) but blastocyst rates (26.37% vs. 35.48%, P &gt; 0.1) were not different. HF_CR, but not HF_CTRL, oocytes showed higher cleavage rates (68.48%, P &lt; 0.001) compared with HF_HF oocytes. Moreover, both HF_CTRL (44.64%, P &lt; 0.05) and HF_CR (59.78%, P &lt; 0.001) oocytes showed improved blastocyst rates when compared to the HF_HF group (26.37%).

Limitations, reasons for caution
Although using a mouse model has several advantages, translating these results to the human setting is a limitation of this study. However, to improve this translatability, an outbred mouse model was used. Additional data will be collected to gain more information regarding the best preconception care intervention advice.

Wider implications of the findings
This research aims to provide fundamental insights in order to be able to formulate clear preconception guidelines to obese women planning for pregnancy. In addition, we aim to find the shortest possible intervention period to improve fertility.

Trial registration number
Not applicable