Obesity is associated with a higher level of pro-inflammatory cytokines in follicular fluid of women undergoing medically assisted procreation (PMA) programs.

INTRODUCTION: Cytokines are glycoproteins that modulate reproductive function through a series of various mechanisms (by both conditioning gonadal steroidogenesis and contributing to the preservation of an inflammatory microenvironment). AIM OF THE STUDY: To evaluate the impact of certain clinical variables (i.e., age, obesity, insulin resistance index, serum antithyroid antibodies serum levels) on the serum concentrations of cytokines TNF-alpha, IL-6, and IL-10 in the follicular fluid of women undergoing a medically assisted procreation (PMA) cycle. MATERIALS AND METHODS: A total of 40 female patients undergoing an intracytoplasmic sperm injection (ICSI) in oocytes, following ovarian stimulation by purified FSH and hCG carried out after suppression of ovarian function. The follicular fluid, obtained by surgical ultrasonography-guided withdrawal, was stored at -30 degrees C. Subsequently the cytokines were assayed by ELISA technique. RESULTS: Women suffering from class II obesity showed follicular levels of TNF-alpha significantly higher (p < 0.05) than women with a normal body mass index (BMI). Significantly higher concentrations of TNF-alpha and IL-6 were found in women with HOMA index > 2.5. Women clinically presenting with concomitant obesity and high serum levels of antithyroid antibodies were found to have higher follicular levels of TNF-alpha and IL-6 (p < 0.05) in comparison with women suffering from obesity only or low antithyroid antibodies levels only, or from both these conditions. CONCLUSION: Obesity is a common clinical condition associated with a higher concentration of inflammatory substances in the follicular fluid of infertile women. It is not understood, as yet, the possible pejorative role exerted by the presence of other clinical conditions, such as insulin resistance and high levels of antithyroid antibodies, that are conditions frequently encountered in the clinical practice.

Adipogenesis is inhibited by brief, daily exposure to high-frequency, extremely low-magnitude mechanical signals.

Obesity, a global pandemic that debilitates millions of people and burdens society with tens of billions of dollars in health care costs, is deterred by exercise. Although it is presumed that the more strenuous a physical challenge the more effective it will be in the suppression of adiposity, here it is shown that 15 weeks of brief, daily exposure to high-frequency mechanical signals, induced at a magnitude well below that which would arise during walking, inhibited adipogenesis by 27% in C57BL/6J mice. The mechanical signal also reduced key risk factors in the onset of type II diabetes, nonesterified free fatty acid and triglyceride content in the liver, by 43% and 39%, respectively. Over 9 weeks, these same signals suppressed fat production by 22% in the C3H.B6-6T congenic mouse strain that exhibits accelerated age-related changes in body composition. In an effort to understand the means by which fat production was inhibited, irradiated mice receiving bone marrow transplants from heterozygous GFP+ mice revealed that 6 weeks of these low-magnitude mechanical signals reduced the commitment of mesenchymal stem cell differentiation into adipocytes by 19%, indicating that formation of adipose tissue in these models was deterred by a marked reduction in stem cell adipogenesis. Translated to the human, this may represent the basis for the nonpharmacologic prevention of obesity and its sequelae, achieved through developmental, rather than metabolic, pathways.

Rapid establishment of chemical and mechanical properties during lamellar bone formation.

The development of prophylaxes and treatments of bone diseases that can effectively increase the strength of bone as a structure necessitates a better understanding of the time course by which chemical properties define the stiffness of the material during primary and secondary mineralization. It was hypothesized that these processes would be relatively slow in the actively growing skeleton. Seven-week-old Sprague-Dawley female rats (n = 8) were injected with multiple fluorochrome labels over a time span of 3 weeks and killed. Chemical and mechanical properties of the tibial mid-diaphysis were spatially characterized between the endocortical and periosteal surface by in situ infrared microspectroscopy and nanoindentation. The phosphate-to-protein ratio of bone 2-6 days old was 20% smaller at the periosteal surface and 22% smaller at the endocortical surface (P < 0.05 each) compared to older intracortical regions. The ratios of carbonate to protein, crystallinity, type A/type B carbonate, collagen cross-linking, and bone elastic modulus did not differ significantly between bone 2-6, 10-14, and 8-22 days old and intracortical regions. Intracortical properties of 10-week-old rats, except for the carbonate-to-protein ratio which was 23% smaller (P < 0.01), were not significantly different from intracortical matrix properties of young adult rats (5 months, n = 4). Spatially, the phosphate-to-protein ratio (R(2) = 0.33) and the phosphate-to-carbonate ratio (R(2) = 0.55) were significantly correlated with bone material stiffness, while the combination of all chemical parameters raised the R(2) value to 0.83. These data indicate that lamellar bone has the ability to quickly establish its mechanical and chemical tissue properties during primary and secondary mineralization even when the skeleton experiences rapid growth.