Rosita Smith

Metabolic Profile in Sons of Women with Polycystic Ovary Syndrome

CONTEXT Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic disorder with strong familial aggregation. It has been demonstrated that parents and brothers of PCOS women exhibit insulin resistance and related metabolic defects. However, metabolic phenotypes in sons of PCOS women have not been described. OBJECTIVE Our objective was to assess the metabolic profiles in sons of women with PCOS during different stages of life: early infancy, childhood, and adulthood. DESIGN Eighty sons of women with PCOS (PCOS(S)) and 56 sons of control women without hyperandrogenism (C(S)), matched for age, were studied. In early infancy, glucose and insulin were determined in the basal sample. In children and adults, a 2-h oral glucose tolerance test was performed with measurements of glucose and insulin. Adiponectin, leptin, C-reactive protein, SHBG, and serum lipids were determined in the basal sample during the three periods. RESULTS During early infancy, PCOS(S) showed higher weight (P = 0.038) and weight sd score (P = 0.031) than C(S). During childhood, weight (P = 0.003), body mass index (BMI) (P < 0.001), BMI sd score (P < 0.001), waist circumference (P = 0.001), total cholesterol (P = 0.007), and low-density lipoprotein cholesterol (P = 0.022) were higher in PCOS(S) compared with C(S), but after adjusting for BMI, these differences were nonsignificant. During adulthood, PCOS(S) exhibited higher weight (P = 0.022), BMI (P = 0.046), and waist circumference (P = 0.028) than C(S). Fasting insulin (P = 0.030), homeostasis model assessment for insulin resistance (P = 0.034), total cholesterol (P = 0.043), low-density lipoprotein cholesterol (P = 0.034), and 2-h insulin (P = 0.006) were also significantly higher and insulin sensitivity index composite significantly lower in PCOS(S) than in C(S) (P = 0.003). After adjusting for BMI, only 2-h insulin and insulin sensitivity index composite remained significantly different. CONCLUSIONS This study indicates that sons of PCOS women exhibit higher body weight from early infancy. In addition, insulin resistance became evident as the subjects got older, which may place them at risk for the development of type 2 diabetes and cardiovascular disease.

Prenatal Testosterone Excess Reduces Sperm Count and Motility

The reproductive system is extremely susceptible to insults from exposure to exogenous steroids during development. Excess prenatal testosterone exposure programs neuroendocrine, ovarian, and metabolic deficits in the female, features seen in women with polycystic ovary disease. The objective of this study was to determine whether prenatal testosterone excess also disrupts the male reproductive system, using sheep as a model system. The extent of reproductive disruption was tested by assessing sperm quantity and quality as well as Leydig cell responsiveness to human chorionic gonadotropin. Males born to mothers treated with 30 mg testosterone propionate twice weekly from d 30 to 90 and with 40 mg testosterone propionate from d 90 to 120 of pregnancy (T-males) showed a significant reduction (P < 0.05) in body weight, scrotal circumference, and sperm count compared with control males. Mean straight line velocity of sperms was also lower in T-males (P < 0.05). Circulating testosterone levels in response to the human chorionic gonadotropin did not differ between groups. These findings demonstrate that exposure to excess testosterone during fetal development has a negative impact on reproductive health of the male offspring, raising concerns relative to unintended human exposure to steroidal mimics in the environment.

Cumulus cell apoptosis changes with exposure to spermatozoa and pathologies involved in infertility

OBJECTIVE To determine whether the incidence of apoptosis in mature oocyte cumulus cells changes after insemination related to infertility. DESIGN Prospective study. SETTING Public hospital and university. PATIENT(S) One hundred women undergoing in vitro fertilization and embryo transfer (IVF-ET). INTERVENTION(S) Collection of cumulus cells from IVF-ET cycles with different infertility etiologies. MAIN OUTCOME MEASURE(S) Detection of apoptosis in cumulus cells; fertilization, embryo quality, and pregnancy rate. RESULT(S) The incubation of cumulus-oocyte-complexes with spermatozoa led to an increase in cumulus cell apoptosis from 34.2 +/- 3.7 to 44.5 +/- 6.3%. After insemination, cumulus cells of poor quality embryos showed a statistically higher apoptotic rate versus cumulus cells of good quality embryos (61.5 +/- 6.4 vs. 40.6 +/- 3.9%). Cumulus cells arising from oocytes with >or=50% fertilization rates after insemination showed higher apoptosis rates did cumulus cells from oocytes with <50% fertilization rates (46.0 +/- 3.7 vs. 33.8 +/- 4.0%). Patients with endometriosis presented higher apoptotic rates before insemination (77.6 +/- 9.06%). Cumulus cells obtained after aspiration showed no differences in their apoptosis rates for the following factors: age of women, aspirated oocytes, estradiol level, fertilization rate, and embryo quality or pregnancy. The apoptotic profile from pregnant women was less than (but not statistically significantly different from) profiles from nonpregnant women. CONCLUSION(S) These results suggest that the incidence of apoptosis in cumulus cells is associated with exposure to spermatozoa and the cause of infertility.

Adenosinetriphosphatase (Mg-ATPase) activity in the plasma membrane of preimplantation mouse embryo as revealed by electron microscopy

SummaryThe ultrastructural localization of Mg2+-ATPase activity was investigated in unfertilized eggs and in preimplantation mouse embryos. Enzyme activity was detected on the entire surface of unfertilized eggs and in one-cell embryos. From the two-cell stage up to the 12-cell embryo the reaction product was localized both at the exposed surface of the embryo and between blastomeres. At the late morula stage, activity was only present on the free surface of the peripheral cells outside the apical tight junctions. In the early blastocyst the membranar reaction was observed both on the outside membrane of the trophoblastic cells and on the inner surface facing the blastocoele, whereas in the late blastocyst the reaction remained unchanged on the outer surface of the embryo but was absent from the membranes bordering the blastocoele.These results are discussed with reference to the modification of the cell surface membrane during preimplantation development.