Ovarian antibodies, FSH and inhibin B: independent markers associated with unexplained infertility.

Premature menopause and unexplained infertility are associated with ovarian antibodies, a marker of ovarian autoimmunity. In premature menopause, FSH is also elevated while in unexplained infertility FSH concentrations are often normal. The relationship of ovarian antibodies and FSH and inhibin B, as markers of follicle function, was investigated in unexplained infertility. Ovarian antibodies were determined by immunoassay in comparison to normal controls (n = 12); 51.9% were positive at two SD (P < 0.05) and 38.5% were positive at three SD above the control mean (P < 0.01). In this study three SD above the control mean was considered positive. In unexplained infertility, three out of 10 (30%) had elevated day 3 FSH (>10 mIU/ml) and ovarian antibodies, while 17/42 (40%) had normal FSH (<10 mIU/ml) and ovarian antibodies. In women with normal FSH, two out of seven (29%) had low inhibin B concentrations (<33 pg/ml) and ovarian antibodies, and 15/35 (43%) had normal inhibin B concentrations (> 33 pg/ml) and ovarian antibodies. Similarly, when women with and without ovarian antibodies were compared there was no difference in mean FSH or mean inhibin B concentrations. Thus, unlike other endocrine autoimmune disorders, hormone concentrations are not predictors of potential ovarian autoimmunity. This suggests that in unexplained infertility ovarian antibodies are an independent marker of potential ovarian failure, and may precede changes in regulatory hormones.

Ovarian autoimmunity: greater frequency of autoantibodies in premature menopause and unexplained infertility than in the general population.

The objective of this study was to: (1) assess the relative prevalence of ovarian, thyroid, nuclear, and cardiolipin antibodies associated with premature menopause and unexplained infertility and (2) compare ovarian and thyroid antibodies in premature menopause, unexplained infertility, and the general population. Autoantibodies were evaluated in women with premature menopause (n = 30), unexplained infertility with (n = 38) or without (n = 15) prior gonadotropin-induced ovulation, and normal cycling controls (n = 12) and in a population of women obtained from a blood bank (n = 53). Antibodies to ovary (OVAB), thyroid (THYAB; thyroid peroxidase and thyroglobulin), cardiolipin, and eight nuclear antigens were assessed by enzyme immunoassay. Organ-specific antibodies (ovary and thyroid) were present with significantly greater frequency than non-organ-specific antibodies (nuclear and cardiolipin) in premature menopause and unexplained infertility (60% (50/83) vs 16% (13/83) respectively; P < 0.0001). OVAB (53%, 44/83) were significantly more frequent than THYAB (30%, 25/83) in premature menopause and unexplained infertility (P = 0.0030). THYAB did not differ among all groups (P = 0.78). In premature menopause and treated or untreated unexplained infertility OVAB frequencies were 53, 61, and 33%, respectively, and were significantly more frequent than in the population (17%) (P = 0.0001). In unexplained infertility, individuals with no prior gonadotropin-induced ovulation had a lower frequency of OVAB than treated individuals (P = 0.07). The frequency distribution of optical density values for OVAB was significantly higher for premature menopause and unexplained infertility than for population or normal cycling women (P < 0.0001). Thus, only ovarian antibodies were significantly more frequent than other antibody markers of autoimmunity in premature menopause and unexplained infertility.

Polycystic ovary syndrome and ovarian autoimmunity--assessment of ovarian antibodies by EIA.

There are conflicting reports of an association of ovarian antibodies, detected by immunofluorescence, with polycystic ovary syndrome (PCOS). The objective of this study was to evaluate the association of ovarian autoimmunity with PCOS. A validated immunoassay for ovarian antibodies was used to assess serum from women with PCOS and with menopause and normal cycling women as controls. The frequency of ovarian antibodies was similar (25%) among the controls and PCOS. Thus, unlike the association of ovarian antibodies detected with this test in patients with unexplained infertility and premature menopause, the prevalence of ovarian antibody in patients with PCOS is not significantly different to controls.

Formation of an activated N-nitroso compound in nitrite-treated fava beans (Vicia faba).

Fava beans are prominent in the diet of the Colombian population at high gastric cancer risk. Upon nitrite treatment under simulated gastric conditions, a potent mutagen was formed as detected by a forward mutation assay using Salmonella typhimurium TM677 without microsomal activation. The promutagen was partially purified by preparative t.l.c. and normal phase h.p.l.c. of the acetone-soluble portion of a dried aqueous extract. The nitrosated promutagen fully accounted for the mutagenicity observed with whole fava beans. One gram of fresh fava beans yielded approximately 0.35 nmol of mutagen. Mutagenicity data indicated that this mutagen was more potent than N-methyl-N'-nitro-N-nitrosoguanidine. The characteristics of the mutagen were typical of an activated N-nitroso compound, that is a compound in which the N-nitroso moiety is attached to an activating group, such as a carbonyl group. Irradiation of the mutagen yielded a Griess positive reaction. By reverse-phase h.p.l.c. photohydrolysis, a single peak could be ascribed to the mutagen. Its stability varied as a function of pH, being most unstable under alkaline conditions. Cysteine and phosphate concentration had no effect on its rate of decomposition, thereby strongly suggesting that the mutagen is an N-nitrosourea. The results obtained in this study support the hypothesis of carcinogenesis via the intragastric production of activated N-nitroso compounds.

Effect of galactose on beta-galactosidase synthesis in Escherichia coli K-12.

In wild-type strains of Escherichia coli K-12, the rate of thiomethylgalactoside (TMG)-induced beta-galactosidase synthesis is decreased in the presence of galactose or glucose. A spontaneous mutant of a K-12 strain, 58-161, which synthesizes beta-galactosidase at a low rate was isolated. In this mutant, galactose, after a lag of about one generation time, evoked the same final differential rate of enzyme synthesis as did the gratuitous inducer TMG. However, constitutive, TMG-induced and galactose-induced synthesis in the mutant were subject to inhibition by exogenous glucose. It is concluded that repression of beta-galactosidase synthesis derived from glucose is distinct from the inhibition derived from galactose.

Role of lac genes in induction of beta-galactosidase synthesis by galactose.

Strain BL1003, a lacO mutant, synthesizes beta-galactosidase constitutively at a low rate. The enzyme is further inducible by d-galactose to the same differential rate as is seen in the presence of an optimal concentration of thiomethylgalactoside. lacY Mutants derived from strain BL1003 are not inducible by galactose, although they synthesize beta-galactosidase at the low constitutive rate characteristic of the parent. Galactose is a weak inducer of beta-galactosidase synthesis in wild-type Escherichia coli K-12, but it is more effective when the wild type has been preinduced with isopropyl-beta-d-thiogalactoside. Nevertheless, the rise in the differential rate of synthesis in response to galactose in a preinduced wild-type culture is much lower than in strain BL1003. Thus, two factors are involved in the induction of strain BL1003 by galactose: the mutant operator and the constitutive permease. The operator has an altered sensitivity to the i product-galactose complex. The low constitutive level of permease enabled the cells, at the high concentrations of galactose used (5 x 10(-2)m), to maintain a sufficient internal concentration for further induction.