Maternal metabolic stress may affect oviduct gatekeeper function

We hypothesized that elevated non-esterified fatty acids (NEFA) modify in vitro bovine oviduct epithelial cell (BOEC) metabolism and barrier function. Hereto, BOECs were studied in a polarized system with 24h-treatments at day 9: 1) CONTROL (0µM NEFA + 0%EtOH), 2) SOLVENT CONTROL (0µM NEFA + 0.45%EtOH), 3) BASAL NEFA (720µM NEFA + 0.45%EtOH in the basal compartment), 4) APICAL NEFA (720µM NEFA + 0.45%EtOH in the apical compartment). FITC-albumin was used for monolayer permeability assessment, and related to Transepithelial Electric Resistance (TER). Fatty acid (FA), glucose, lactate and pyruvate concentrations were measured in spent medium. Intracellular lipid droplets (LD) and FA-uptake were studied using Bodipy 493/503 and immunolabelling of FA-transporters (FAT/CD36, FABP3 and caveolin1). BOEC-mRNA was retrieved for qRT-PCR. Results revealed that APICAL NEFA reduced relative TER-increase (46.85%) during treatment, and increased FITC-albumin flux (27.59%) compared to other treatments. In BASAL NEFA, FAs were transferred to the apical compartment as free FAs: mostly palmitic and oleic acid increased, respectively 56.0 % and 33.5% of initial FA-concentrations. APICAL NEFA allowed no FA-transfer, but induced LD-accumulation and upregulated FA-transporter expression (↑CD36, ↑FABP3, ↑CAV1-protein-expression). Gene expression in APICAL NEFA indicated increased anti-apoptotic (↑BCL2) and anti-oxidative (↑SOD1) capacity, upregulated lipid metabolism (↑CPT1, ↑ACSL1 and ↓ACACA), and FA-uptake (↑CAV1). All treatments had similar carbohydrate metabolism and oviduct function specific gene expression (=OVGP1, ESR1, FOXJ1). Overall, elevated NEFAs affected BOEC-metabolism and barrier function differently depending on NEFA-exposure side. Data substantiate the concept of the oviduct as a gatekeeper that may actively alter early embryonic developmental conditions

Differential effects of high and low glucose concentrations during lipolysis-like conditions on bovine in vitro oocyte quality, metabolism and subsequent embryo development

Lipolytic metabolic conditions are traditionally associated with elevated non-esterified fatty acid (NEFA) concentrations, but may also be accompanied by hyperglycaemia in obesity or by hypoglycaemia during a negative energy balance status. Elevated NEFA concentrations disrupt oocyte and embryo development and quality, but little is known about whether the effects of lipolytic conditions on oocyte developmental competence are modulated by glucose availability. To answer this, bovine cumulus-oocyte complexes (COCs) were matured under different conditions physiological NEFA (72M) and normal glucose (5.5mM), pathophysiologically high NEFA (420M) and normal glucose, high NEFA and high glucose (9.9mM), high NEFA and low glucose (2.8mM). Developmental potential, cumulus expansion and metabolism of COCs exposed to high NEFA and low glucose were affected to a greater extent compared with COCs matured under high NEFA and high glucose conditions. High NEFA and high glucose conditions caused a moderate increase in oocyte reactive oxygen species compared with their high NEFA and low glucose or control counterparts. Blastocyst metabolism and the transcriptome of metabolic and oxidative stress-related genes were not affected. However, both lipolytic conditions associated with hyper-or hypoglycaemia led to surviving embryos of reduced quality with regards to apoptosis and blastomere allocation

Nutrition and maternal metabolic health in relation to oocyte and embryo quality : critical views on what we learned from the dairy cow model

Although fragmented and sometimes inconsistent, the proof of a vital link between the importance of the physiological status of the mother and her subsequent reproductive success is building up. High-yielding dairy cows are suffering from a substantial decline in fertility outcome over past decades. For many years, this decrease in reproductive output has correctly been considered multifactorial, with factors including farm management, feed ratios, breed and genetics and, last, but not least, ever-rising milk production. Because the problem is complex and requires a multidisciplinary approach, it is hard to formulate straightforward conclusions leading to improvements on the ‘work floor’. However, based on remarkable similarities on the preimplantation reproductive side between cattle and humans, there is a growing tendency to consider the dairy cow’s negative energy balance and accompanying fat mobilisation as an interesting model to study the impact of maternal metabolic disorders on human fertility and, more specifically, on oocyte and preimplantation embryo quality. Considering the mutual interest of human and animal scientists studying common reproductive problems, this review has several aims. First, we briefly introduce the ‘dairy cow case’ by describing the state of the art of research into metabolic imbalances and their possible effects on dairy cow reproduction. Second, we try to define relevant in vitro models that can clarify certain mechanisms by which aberrant metabolite levels may influence embryonic health. We report on recent advances in the assessment of embryo metabolism and meantime critically elaborate on advantages and major limitations of in vitro models used so far. Finally, we discuss hurdles to be overcome to successfully translate the scientific data to the field.</jats:p