T. Zore

Sex differences in obesity, lipid metabolism, and inflammation—A role for the sex chromosomes?

Background Sex differences in obesity and related diseases are well established. Gonadal hormones are a major determinant of these sex differences. However, sex differences in body size and composition are evident prior to exposure to gonadal hormones, providing evidence for gonadal-independent contributions attributable to the XX or XY sex chromosome complement. Large-scale genetic studies have revealed male/female differences in the genetic architecture of adipose tissue amount and anatomical distribution. However, these studies have typically neglected the X and Y chromosomes. Scope of the review Here we discuss how the sex chromosome complement may influence obesity, lipid levels, and inflammation. Human sex chromosome anomalies such as Klinefelter syndrome (XXY), as well as mouse models with engineered alterations in sex chromosome complement, support an important role for sex chromosomes in obesity and metabolism. In particular, the Four Core Genotypes mouse model—consisting of XX mice with either ovaries or testes, and XY mice with either ovaries or testes—has revealed an effect of X chromosome dosage on adiposity, hyperlipidemia, and inflammation irrespective of male or female gonads. Mechanisms may include enhanced expression of genes that escape X chromosome inactivation. Major conclusions Although less well studied than effects of gonadal hormones, sex chromosomes exert independent and interactive effects on adiposity, lipid metabolism, and inflammation. In particular, the presence of two X chromosomes has been associated with increased adiposity and dyslipidemia in mouse models and in XXY men. The enhanced expression of genes that escape X chromosome inactivation may contribute, but more work is required.

Mode of conception does not appear to affect placental volume in the first trimester

OBJECTIVEnTo study whether infertility treatments, including IVF and non-IVF fertility treatments, are associated with diseases of placental insufficiency in early gestation. First trimester placental volumes by ultrasound and chorionic villi weight during sampling (CVS) were performed to detect differences between pregnancies conceived spontaneously versus with fertility treatments.nnnDESIGNnRetrospective cohort.nnnSETTINGnAcademic tertiary center.nnnPATIENT(S)nWomen with singleton pregnancies undergoing CVS and first trimester ultrasound from April 2007 to Novemberxa02015.nnnINTERVENTION(S)nEstimated placental volume (EPV) was calculated from ultrasound images using a validated computation and CVS estimated tissue weight was performed using a validated visual analogue scale.nnnMAIN OUTCOME MEASURE(S)nAdjusted linear regression was used to compare EPV and CVS weight based on mode of conception.nnnRESULT(S)nA total of 1,977 spontaneous and 334 conceived with fertility treatments (133 non-IVF and 201 IVF) pregnancies were included. Significant differences in maternal age, gravidity, hypertension, and smoking status were identified. EPV and CVS weight were correlated with maternal age, gestational age, and maternal hypertension. Adjusted linear regression showed no difference in EPV in pregnancies conceived with fertility treatments versus spontaneously. The CVS weight was significantly lower in the IVF conceptions in unadjusted univariate analyses. However, after adjusted regression, this was no longer significant.nnnCONCLUSION(S)nMode of conception does not appear to affect first trimester placental size. As differences in maternal age, hypertension, and smoking status differ among the groups and are correlated to placental size, it may be the underlying patient population leading to abnormal placentation and insufficiency, not the fertility treatments used.

Polycystic Ovarian Syndrome: Long-Term Health Consequences

Polycystic ovarian syndrome (PCOS) is the most common endocrinopathy in women and can be associated with significant adverse sequelae that can affect overall long-term health and well-being. This review provides a succinct but comprehensive overview of our current understanding concerning the known morbidities of PCOS, beginning with a review of the importance of the different phenotypes of PCOS in determining long-term morbidity, the confounding impact of obesity on health outcomes in PCOS, and the immediate short-term consequences of the disorder (including dermatologic, reproductive, and mood disturbances). The longer-term morbidities of PCOS are then reviewed including metabolic consequences (impaired glucose tolerance and type 2 diabetes mellitus, metabolic syndrome, and nonalcoholic fatty liver disease), dyslipidemia and vascular dysfunction (including hypertension and increased incidences of cerebrovascular accidents and thromboembolisms on oral contraceptives), neoplastic (primarily endometrial adenocarcinoma), and mental health disorders (including greater incidences of depressive and anxiety disturbances and psychosexual dysfunction). In conclusion, strategies for the prevention and amelioration of long-term morbidities in PCOS are presented.