Interaction of apolipoprotein E gene polymorphisms on miscarriage risk in black and white American women.

OBJECTIVE: To evaluate whether [1] apolipoprotein E (APOE) polymorphisms can differentially regulate miscarriage risk and [2] whether this genotype effect could also be modulated by the race within populations. DESIGN: Data were derived from the Coronary Artery Risk Development in Young Adults (CARDIA), a longitudinal study with black and white participants from four U.S. SETTING: Not applicable. PATIENT(S): Women without miscarriages (controls) and women who miscarried at least once (cases). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): A group of women (n = 1,372) successfully followed for 25 years and with their APOE alleles identified were analyzed for miscarriage risk throughout their reproductive life. Additionally, a larger longitudinal analysis encompassing all the participants who had their APOE characterized (n = 2,140) was also performed for the association between APOE and miscarriage risk. RESULT(S): In white women followed up for 25 years, the odds ratio for miscarriage associated with APOE*2 allele presence was 1.61 (95% confidence interval, 1.04-2.50) compared with APOE*33 carriers. This was a race-dependent phenomenon as no associations between APOE alleles and miscarriage was observed in black women. Likewise, Cox regression analysis showed that cumulative miscarriage risk in white women was 37.2% in the APOE*2 carriers compared with 27.8% and 24.8% in APOE*33 and APOE*4 carriers, respectively. With APOE*33 as the reference, the age-adjusted hazard ratio associated with carrying the APOE*2 allele was 1.47 (95 confidence interval, 1.06-2.05). CONCLUSION(S): This variable miscarriage risk, produced by an interaction between genotype and race, may reconcile, at least partially, the conflicting reports of the association of APOE and miscarriage risk.

Effects of adipocyte-secreted factors on decidualized endometrial cells: modulation of endometrial receptivity in vitro

Obesity is defined as an excessive accumulation of adipose tissue that may lead to health complications. Mounting evidence indicates that obesity has a negative impact on fertility. Yet, the link between adipose tissue biology and infertility remains unclear. We aimed to investigate the communication between the adipose tissue and the reproductive system and the importance of this cross talk for the development of a receptive endometrium. To that end, we generated an in vitro model with endometrial and adipocyte cell lines. Sexual hormones, progesterone and estradiol, were used to decidualize endometrial cells and sensitize adipocytes. Decidualization produced a simultaneous increase of adipokine receptors in endometrial cells paralleling changes in their receptivity status. Furthermore, sensitization of 3T3-L1 adipocytes increased mRNA levels of leptin and resistin and decreased the expression of adiponectin and chemerin levels. This was accompanied by increased isoproterenol-induced lipolysis and reduced insulin-stimulated glucose uptake. Lastly, conditioned culture medium of those sensitized adipocytes was used to feed endometrial cells. This treatment resulted in (i) upregulation of genes previously identified as positive regulators of endometrial receptivity, such as leukemia inhibitory factor and glutathione peroxidase 3, and (ii) downregulation of interleukin-15 and mucin1, both genes negatively related with endometrial receptivity. Our results indicate that the endocrine communication between adipose tissue and the reproductive system is bidirectional and stress the importance of the adipose tissue to modulate the reproductive fitness

Effects of adipocyte-secreted factors on decidualized endometrial cells: modulation of endometrial receptivity in vitro.

Obesity is defined as an excessive accumulation of adipose tissue that may lead to health complications. Mounting evidence indicates that obesity has a negative impact on fertility. Yet, the link between adipose tissue biology and infertility remains unclear. We aimed to investigate the communication between the adipose tissue and the reproductive system and the importance of this cross talk for the development of a receptive endometrium. To that end, we generated an in vitro model with endometrial and adipocyte cell lines. Sexual hormones, progesterone and estradiol, were used to decidualize endometrial cells and sensitize adipocytes. Decidualization produced a simultaneous increase of adipokine receptors in endometrial cells paralleling changes in their receptivity status. Furthermore, sensitization of 3T3-L1 adipocytes increased mRNA levels of leptin and resistin and decreased the expression of adiponectin and chemerin levels. This was accompanied by increased isoproterenol-induced lipolysis and reduced insulin-stimulated glucose uptake. Lastly, conditioned culture medium of those sensitized adipocytes was used to feed endometrial cells. This treatment resulted in (i) upregulation of genes previously identified as positive regulators of endometrial receptivity, such as leukemia inhibitory factor and glutathione peroxidase 3, and (ii) downregulation of interleukin-15 and mucin1, both genes negatively related with endometrial receptivity. Our results indicate that the endocrine communication between adipose tissue and the reproductive system is bidirectional and stress the importance of the adipose tissue to modulate the reproductive fitness.