Despite decades of studying muscle glycogen in many metabolic situations, surprisingly little is known regarding its regulation. Glycogen is a dynamic and vital metabolic fuel that has very limited energetic capacity. Thus its regulation is highly complex and multifaceted. The stores in muscle are not homogeneous and there appear to be various metabolic pools. Each granule is capable of independent regulation and fundamental aspects of the regulation appear to be associated with a complex set of proteins (some are enzymes and others serve scaffolding roles) that associate both with the granule and with each other in a dynamic fashion. The regulation includes altered phosphorylation status and often translocation as well. The understanding of the roles and the regulation of glycogenin, protein phosphatase 1, glycogen targeting proteins, laforin and malin are in their infancy. These various processes appear to be the mechanisms that give the glycogen granule precise, yet dynamic regulation.

Background Obesity is known to be associated with inflammation, oxidative stress and a resulting reduction in sperm DNA integrity. Importantly, obesity is also reported to be associated with an increase in intestinal permeability with the passage of intestinal bacteria into the circulation (metabolic endotoxemia) that triggers a systemic state of inflammation and resultant oxidative stress. Therefore, we hypothesised that this obesity related increase in intestinal permeability and resultant metabolic endotoxemia (ME) may activate inflammation within the male reproductive tract, leading to increased reactive oxygen species production, sperm oxidative stress and a decline in DNA integrity. Results Our pilot study of 37 infertile men confirmed a significant positive correlation between body mass index (BMI), increased intestinal permeability (serum zonulin), metabolic endotoxaemia (LBP), sperm DNA oxidative damage (seminal 8 OhDG) and increasing levels of sperm DNA fragmentation (Halosperm). Metabolic endotoxemia was positively correlated with increasing levels of sperm DNA oxidative damage with this relationship remaining significant, even after adjustment for relevant confounders such as age, BMI and days of abstinence. These observations suggest that metabolic endotoxemia and its associated oxidative stress may be a key driver of sperm DNA damage in obese men. Conclusion This study confirms a link between obesity, increasing intestinal permeability and endotoxin exposure, and oxidative mediated sperm DNA damage. This warrants further investigation to fully understand the effect of metabolic endotoxemia on male reproductive function which could result in the new therapies to improve male fertility potential.

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Obesity is known to be associated with impaired testicular function potentially resulting in androgen deficiency and subfertility. While the underlying cause of obesity-related male hypogonadism is multi-factorial, here, we investigated the impact of dietary fat on testicular endocrine function. Ingestion of a high-fat "fast food" mixed meal, a common practice for obese men, produced a 25% fall in serum testosterone within an hour of eating, with levels remaining suppressed below fasting baseline for up to 4 hr. These changes in serum testosterone were not associated with any significant changes in serum gonadotrophins. The nadir in serum testosterone preceded the post-prandial increase in serum IL-6/IL-17 by several hours, suggesting that inflammation was unlikely the cause. Furthermore, intravenous administration of fat (Intralipid) had no impact on testosterone levels, while an identical oral dose of fat did suppress testosterone. These results suggest that fat does not directly impair Leydig cell function, but rather the passage of fat through the intestinal tract elicits a response that indirectly elicits a post-prandial fall in testosterone. K E Y W O R D Sfat, food, inflammation, post-prandial, testosterone

Oxidative stress is prevalent among infertile men and is a significant cause of sperm DNA damage. Since sperm DNA damage may reduce embryo quality and increase miscarriage rates, it is possible that untreated sperm oxidative stress may impair in vitro fertilization (IVF) live birth rates. Given that the antioxidant Menevit is reported to reduce sperm DNA damage, it was hypothesized that men's consumption of this supplement may alter IVF outcomes. Therefore, a retrospective cohort study was conducted analyzing outcomes for couples undergoing their first fresh embryo transfer. Men were classified as controls if they were taking no supplements, health conscious controls if taking “general health” supplements, or Menevit users. Men with karyotype abnormalities, or cycles using donated, frozen and surgically extracted sperm were excluded. Among the final study cohort of 657 men, live birth rates were significantly higher in Menevit users than controls (multivariate adjusted odds ratio [OR]: 1.57, 95% confidence interval [CI]: 1.01–2.45, P = 0.046), but not between controls taking no supplements and those using general health supplements, thereby suggesting that potential health conscious behavior in supplement users is unlikely responsible for the superior outcomes in Menevit users. Interestingly, in a post hoc sensitivity analysis, live birth rates among Menevit users were statistically superior to controls for lean men (OR: 2.73, 95% CI: 1.18–6.28; P = 0.019), not their overweight/obese counterparts (OR: 1.29, 95% CI: 0.75–2.22, P = 0.37). The results of this large cohort study therefore support a positive association between men's use of the Menevit antioxidant during IVF treatment and live birth rates, especially in lean individuals.

Vaginal ultrasound is the most effective method of imaging the contents of the true pelvis in the female. Saline influsion sonohysterography (SIS) is a simple refinement of the standard vaginal sonographic exam. Here, we briefly describe and demonstrate our use of this latter technique.

Prolonged endometritis is the most common cause of infertility in mares causing great economic impact. Many mares fail to be diagnosed with endometritis despite the availability of different diagnostic tests. Therefore, the purpose of this study was to compare endometrial swab, low-volume lavage (LVL) and endometrial biopsy as diagnostic methods for endometritis and to report the prevalence of this disease in a referral practice population. Fifty-one mares presenting for routine breeding or infertility work-up were examined by transrectal ultrasonography, before collecting samples for endometrial culture and cytology. Seven of the 51 mares had all the tests except endometrial biopsy. A mare was classified positive for endometritis if she demonstrated two or more of the following 5 criteria on a checklist (new gold standard; NGS): (1) abnormal clinical findings (any of uterine fluid on ultrasound, or excessive oedema for follicular size, or history of subfertility); (2) abnormal gross character of the LVL fluid: (cloudy, discolored, debris) before centrifugation; (3) positive endometrial cytology (≥1 neutrophil per high power field, or ≥1% (1 : 100) neutrophil to epithelial cell ratio on cytology); (4) bacterial growth on culture of the LVL pellet; and (5) histological evidence of inflammation (acute, chronic, and mixed) detected on endometrial biopsy. Data were analysed via kappa coefficient (k) and frequencies were calculated for sensitivity and positive predictive value (PPV) with biopsy being the gold standard and compared to the NGS. Endometritis was diagnosed in 35/44 (79.5%) mares by biopsy (5/35 had acute endometritis, 12/35 had chronic; 18/35 had a combination of acute and chronic endometritis). Based on the endometritis criteria (2/5 items on the checklist), 33/51 (64.7%) mares were diagnosed to have endometritis. All 11 of the barren mares were diagnosed by the checklist, while two of these 11 mares had no evidence of endometritis by biopsy, but had clinical signs or cloudy efflux. The character of the endometrial flush was 45% sensitive (k = 0.046), while culture was 22% sensitive, when compared to endometrial biopsy. When each criterion for endometritis was compared against the NGS, endometrial biopsy was the most sensitive diagnostic method (sensitivity = 86%). Abnormal clinical findings showed moderate agreement with the NGS (k = 0.4138), with a sensitivity of 62% and P = 0.0019. Positive endometrial cytology showed similar agreement (k = 0.3761), and sensitivity (sensitivity = 64%, and P = 0.0069). These studies have also shown the importance of using laboratory data in light of clinical findings, since they have shown that no test by itself is sensitive enough to diagnose a mare with subclinical endometritis, and that this disease might be under diagnosed. Since this study was performed in a referral hospital, there may have been a higher prevalence of endometritis than found in general clinical practice. An endometritis checklist could be used in cases where endometrial biopsies are not readily available.