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Obesity, known to cause a systemic elevation in monocyte chemotactic protein-1 (MCP-1), adversely affects normal ovarian function. The aim of this study was to determine whether MCP-1 plays a role in ovarian dysfunction that is related to obesity induced by high-fat (HF) diet intake. Wild type (WT) C57BL/6J mice were fed either normal chow (NC) (Group 1, control group) or HF diet (Group 2). To assess whether MCP-1 is involved in HF-diet-induced ovarian dysfunction, MCP-1 knock-out mice were fed HF diet (Group 3). Body weight, body fat composition, number of oocytes collected following ovarian superovulation with gonadotropins, ovarian macrophage markers and expression of genes important in folliculogenesis and steroidogenesis were quantified in the 3 groups of animals. Animals in Group 2 gained significant body weight and body mass, produced the fewest number of oocytes following superovulation, and had significant alterations in ovarian genes involved in folliculogenesis and steroidogenesis as well as genes involved in inflammation. Although animals in Group 3 had the highest body weight and body fat composition, they produced similar number of oocytes compared to animals in Group 1 but had different ovarian gene expression compared to Group 2. These findings suggest that MCP-1 gene knockout could reverse some of the adverse effects of obesity induced by HF diet intake. Future studies assessing ovarian histology in MCP-1 knock out mouse model will confirm our findings. MCP-1 inhibition could represent a future therapeutic target to protect ovarian health from the adverse effects of HF diet ingestion.

The androgen receptor (AR) has context-dependent roles in breast cancer growth and progression. Overall, high tumor AR levels predict a favorable patient outcome, but several studies have established a tumor promotional role for AR, particularly in supporting the growth of estrogen receptor positive (ER-positive) breast cancers after endocrine therapy. Our previous studies have demonstrated that obesity promotes mammary tumor progression after ovariectomy (OVX) in a rat model of postmenopausal breast cancer. Here, we investigated a potential role for AR in obesity-associated post-OVX mammary tumor progression following ovarian estrogen loss. In this model, we found that obese but not lean rats had nuclear localized AR in tumors that progressed 3 weeks after OVX, compared to those that regressed. AR nuclear localization is consistent with activation of AR-dependent transcription. Longer-term studies (8 weeks post-OVX) showed that AR nuclear localization and expression were maintained in tumors that had progressed, but AR expression was nearly lost in tumors that were regressing. The anti-androgen enzalutamide effectively blocked tumor progression in obese rats by promoting tumor necrosis and also prevented the formation of new tumors after OVX. Neither circulating nor mammary adipose tissue levels of the AR ligand testosterone were elevated in obese compared to lean rats; however, IL-6, which we previously reported to be higher in plasma from obese versus lean rats, sensitized breast cancer cells to low levels of testosterone. Our study demonstrates that, in the context of obesity, AR plays a role in driving ER-positive mammary tumor progression in an environment of low estrogen availability, and that circulating factors unique to the obese host, including IL-6, may influence how cancer cells respond to steroid hormones.

Objective: To determine whether obesity alters genes important in cellular growth and inflammation in human cumulus granulosa cells (GCs)., Methods: Eight reproductive-aged women who underwent controlled ovarian hyperstimulation followed by oocyte retrieval for in vitro fertilization were enrolled. Cumulus GC RNA was extracted and processed for microarray analysis on Affymetrix Human Genome U133 Plus 2.0 chips. Gene expression data were validated on GCs from additional biologically similar samples using quantitative real-time polymerase chain reaction (RT-PCR). Comparison in gene expression was made between women with body mass index (BMI) <25 kg/m(2) (group 1; n = 4) and those with BMI ≥25 kg/m(2) (group 2; n = 4)., Results: Groups 1 and 2 had significantly different BMI (21.4 ± 1.4 vs 30.4 ± 2.7 kg/m(2), respectively; P = .02) but did not differ in age (30.5 ± 1.7 vs 32.7 ± 0.3 years, respectively; P = .3). Comparative analysis of gene expression profiles by supervised clustering between group 1 versus group 2 resulted in the selection of 7 differentially expressed genes: fibroblast growth factor 12 (FGF-12), protein phosphatase 1-like (PPM1L), zinc finger protein multitype 2 (ZFPM2), forkhead box M1 (FOXM1), cell division cycle 20 (CDC20), interleukin 1 receptor-like 1 (IL1RL1), and growth arrest-specific protein 7 (GAS7). FOXM1, CDC20, and GAS7 were downregulated while FGF-12 and PPM1L were upregulated in group 2 when compared to group 1. Validation with RT-PCR confirmed the microarray data except for ZFPM2 and IL1RL. As BMI increased, expression of FOXM1 significantly decreased (r = -.60, P = .048)., Conclusions: Adiposity is associated with changes in the expression of genes important in cellular growth, cell cycle progression, and inflammation. The upregulation of the metabolic regulator gene PPM1L suggests that adiposity induces an abnormal metabolic follicular environment, potentially altering folliculogenesis and oocyte quality., (© The Author(s) 2015.)

Objective: Previous studies regarding the effect of obesity on serum anti-müllerian hormone (AMH) levels have been conflicting. Our aim was to determine the effect of obesity on serum AMH levels among women from different racial backgrounds., Methods: The medical records of 350 women (159 Caucasian, 99 African-American, 58 Hispanic, 34 Asian with ages 16-46) evaluated for infertility at an academic-affiliated center and who had AMH levels measured as part of their evaluation were reviewed. Age, AMH, body mass index (BMI), self-reported race, etiology of infertility, smoking history, maximum serum early follicular follicle-stimulating hormone (FSH) levels, antral follicle count (AFC), and history of ovarian surgery, chemotherapy, or radiotherapy were recorded., Results: Age correlated negatively with AMH and antral follicle count across all races (p < 0.05). After adjusting for age, polycystic ovary syndrome diagnosis, and smoking, elevated BMI had a negative correlation with AMH in Caucasian women (β = 0.17, p = 0.01) but not in African-American, Hispanic, or Asian women., Conclusion: Elevated BMI correlates negatively with AMH in Caucasian women but not in African-American, Hispanic, or Asian women. Additional studies are needed to elucidate further the effect of race on the interaction between obesity and ovarian reserve.

Obese postmenopausal women have increased risk of breast cancers with poorer clinical outcomes than their lean counterparts. However, the mechanisms underlying these associations are poorly understood. Rodent model studies have recently identified a period of vulnerability for mammary cancer promotion, which emerges during weight gain after the loss of ovarian function (surgical ovariectomy; OVX). Thus, a period of transient weight gain may provide a life cycle-specific opportunity to prevent or treat postmenopausal breast cancer. We hypothesized that a combination of impaired metabolic regulation in obese animals prior to OVX plus an OVX-induced positive energy imbalance might cooperate to drive tumor growth and progression. To determine if lean and obese rodents differ in their metabolic response to OVX-induced weight gain, and whether this difference affects later mammary tumor metabolism, we performed a nutrient tracer study during the menopausal window of vulnerability. Lean animals preferentially deposited excess nutrients to mammary and peripheral tissues rather than to the adjacent tumors. Conversely, obese animals deposited excess nutrients into the tumors themselves. Notably, tumors from obese animals also displayed increased expression of the progesterone receptor (PR). Elevated PR expression positively correlated with tumor expression of glycolytic and lipogenic enzymes, glucose uptake, and proliferation markers. Treatment with the antidiabetic drug metformin during ovariectomy-induced weight gain caused tumor regression and downregulation of PR expression in tumors. Clinically, expression array analysis of breast tumors from postmenopausal women revealed that PR expression correlated with a similar pattern of metabolic upregulation, supporting the notion that PR+ tumors have enhanced metabolic capacity after menopause. Our findings have potential explanative power in understanding why obese, postmenopausal women display an increased risk of breast cancer.

Background: Male infertility affects approximately 6% of reproductive-aged men. It has been suggested that overweight men or men with obese body mass index (BMI) experience prolonged time to pregnancy, though the influence of male BMI on fertility remains understudied., Aims: We hypothesized that BMI is inversely correlated with fertility, manifested by reduced sperm concentration, motility, and morphology., Methods: Males of age 18 to 50 with semen analyses and self-reported BMI were included (n = 530). Patient parameters analyzed included age, BMI, smoking, urological, and fertility history. Leutinizing hormone (LH), Follicle-stimulating hormone, testosterone, steroid hormone-binding globulin (SHBG) and free androgen index (FAI) levels (n = 55), and selective serotonin reuptake inhibitor (SSRI) use (n = 12) were also measured., Results: The men in this study had a mean BMI of 28.2 ± 4.9 kg/m(2) (range = 15-60), which is considered overweight, and a mean semen concentration of 55.4 ± 46.8 million/mL, which is in normal range, according to WHO standard. No consistent relationship was observed between increasing BMI and sperm concentration, motility, or morphology, although the testosterone levels trended downward with increasing BMI; there was a suggestion for decreased sperm concentration in current smokers. Men treated with combination SSRI and other psychotropic agent therapy (n = 12) had significantly reduced sperm motility (P = .009). Not unexpectedly, prior urological surgery (n = 77) was associated with lower sperm concentration (P = .0001) and morphology (P = .0008). When in vitro fertilization-embryo transfer (IVF-ET) was used as a treatment modality (n = 121), male BMI was not a significant predictor of clinical pregnancy (P = .06)., Conclusions: In our study, we did not observe a significant association between male BMI and sperm concentration, motility or morphology, or clinical pregnancy following IVF-ET. Significantly, SSRI use may affect sperm parameters negatively.

A majority of psychiatric medications are known to generate weight gain and ultimately obesity in some patients. The authors undertook a comprehensive literature review in order to provide a better understanding of novel treatment options in regards to alleviating weight gained by use of antidepressants, antipsychotics, and mood stabilizers. There are no agents for management of this weight gain approved by the Food and Drug Administration (FDA), and existing studies on options are mainly uncontrolled, small-scale projects with limited power to produce coherent conclusions. There is a clear need for larger studies on existing options, and future psychotropics without these side-effects are currently in the pipeline.

A majority of psychiatric medications are known to generate weight gain and ultimately obesity in some patients. There is much speculation about the prevalence of weight gain and the degree of weight gain during acute and longitudinal treatment, but consensus shows that weight gain is prominent. The present review looked at the aetiology and cause of weight gain associated with psychotropic use and presents hypotheses as to why patients gain weight on antipsychotics, mood stabilizers and antidepressants. It is found that most psychotropic medications induce some weight gain, and clinicians are encouraged to utilize active interventions to alleviate the weight gain in order to prevent more serious obesity related comorbidities.

A majority of psychiatric medications are known to generate weight gain and ultimately obesity in some patients. There is much speculation about the prevalence of weight gain and the degree of weight gain during acute and longitudinal treatment with these agents. There is newer literature looking at the aetiology of this weight gain and the potential treatments being used to alleviate this side-effect. We found solid evidence that weight gain is often associated with the mood stabilizers, and antipsychotics and antidepressants. Only few weight neutral or weight loss producing psychotropics are available, and weight gain, outside of an immediate side-effect, may generate secondary side-effects and medical comorbidity. Weight gain may cause hypertension, diabetes, osteoarthritis, sedentary lifestyle, coronary artery disease, etc. Given the likelihood of inducing weight gain with psychotropic medications and the longitudinal impact on physical health, a thorough literature review is warranted to determine the epidemiology, aetiology and treatment options of psychotropic-induced weight gain.