Menstrual function among women exposed to polybrominated biphenyls: A follow-up prevalence study

BACKGROUND: Alteration in menstrual cycle function is suggested among rhesus monkeys and humans exposed to polybrominated biphenyls (PBBs) and structurally similar polychlorinated biphenyls (PCBs). The feedback system for menstrual cycle function potentially allows multiple pathways for disruption directly through the hypothalamic-pituitary-ovarian axis and indirectly through alternative neuroendocrine axes. METHODS: The Michigan Female Health Study was conducted during 1997–1998 among women in a cohort exposed to PBBs in 1973. This study included 337 women with self-reported menstrual cycles of 20–35 days (age range: 24–56 years). Current PBB levels were estimated by exponential decay modeling of serum PBB levels collected from 1976–1987 during enrollment in the Michigan PBB cohort. Linear regression models for menstrual cycle length and the logarithm of bleed length used estimated current PBB exposure or enrollment PBB exposure categorized in tertiles, and for the upper decile. All models were adjusted for serum PCB levels, age, body mass index, history of at least 10% weight loss in the past year, physical activity, smoking, education, and household income. RESULTS: Higher levels of physical activity were associated with shorter bleed length, and increasing age was associated with shorter cycle length. Although no overall association was found between PBB exposure and menstrual cycle characteristics, a significant interaction between PBB exposures with past year weight loss was found. Longer bleed length and shorter cycle length were associated with higher PBB exposure among women with past year weight loss. CONCLUSION: This study suggests that PBB exposure may impact ovarian function as indicated by menstrual cycle length and bleed length. However, these associations were found among the small number of women with recent weight loss suggesting either a chance finding or that mobilization of PBBs from lipid stores may be important. These results should be replicated with larger numbers of women exposed to similar lipophilic compounds

An Asymmetric Opening of HIV-1 Envelope Mediates Antibody-Dependent Cellular Cytotoxicity

The HIV-1 envelope glycoprotein (Env) (gp120-gp41)3 is the target for neutralizing antibodies and antibody-dependent cellular cytotoxicity (ADCC). HIV-1 Env is flexible, sampling different conformational states. Before engaging CD4, Env adopts a closed conformation (State 1) that is largely antibody resistant. CD4 binding induces an intermediate state (State 2), followed by an open conformation (State 3) that is susceptible to engagement by antibodies that recognize otherwise occluded epitopes. We investigate conformational changes in Env that induce ADCC in the presence of a small-molecule CD4-mimetic compound (CD4mc). We uncover an asymmetric Env conformation (State 2A) recognized by antibodies targeting the conserved gp120 inner domain and mediating ADCC. Sera from HIV+ individuals contain these antibodies, which can stabilize Env State 2A in combination with CD4mc. Additionally, triggering State 2A on HIV-infected primary CD4+ T cells exposes epitopes that induce ADCC. Strategies that induce this Env conformation may represent approaches to fight HIV-1 infection