Turner Syndrome and Fertility

Turner syndrome (TS) is tightly associated with hypergonadotropic hypogonadism and ovarian dysgenesis, typically resulting in infertility in the great majority of patients. Therefore females with TS are usually treated with female sex steroids from 11–12 years of age until the normal age of natural menopause of around 53–54 years of age. Infertility is rated among females with TS as a distressing concern and a detractor from a good quality of life. Options for motherhood for females with TS has expanded during recent years. Originally, only adoption was an option, unless of course for the small minority of TS females that still has ovarian function and are capable of achieving pregnancy through normal means. Oocyte donation has become the mainstream option in many countries and seems to work well, especially if patients have been treated with optimal estrogen and gestagen for a prolonged time before the intervention. It comes with an increased risk of cardiovascular complications and TS oocyte donation pregnancies are viewed as high risk pregnancies necessitating increased vigilance. Oocyte cryopreservation of own oocytes is also becoming an option in a select group of TS and has special challenges. Ovarian tissue cryopreservation is a promising new techniques that has been applied successfully in children with cancer. Currently, several trials are running around the world evaluating this techniques in TS. The genetics and genomics behind the ovarian dysgenesis seen in TS is not understood, but new studies have elucidated global changes in DNA methylation and RNA expression in blood from persons with TS and it is likely that similar changes are present in the ovaries. We still, however, need more thorough research to fully uncover the genetic background of ovarian failure in TS. Gene expression studies and methylation analysis from ovarian TS tissues still needs to be performed.     

血清抑制素B早期预测卵巢储备功能下降及干预治疗的临床价值

目的:探讨血清抑制素B(INHB)早期预测卵巢储备功能的临床价值及干预治疗后对其妊娠率的影响。方法:通过检测血清抑制素B水平筛查出202例卵巢储备功能下降导致不孕的患者,随机分为A、B两组各101例。A组未经治疗直接促排卵,B组经人工周期治疗后促排卵,观察两组的周期妊娠率、临床妊娠率及B组治疗前后激素水平的变化。结果:A组周期妊娠率、临床妊娠率均低于B组,差异均有统计学意义(P<0.05);B组INHB水平治疗后较治疗前升高,差异有统计学意义(P<0.05)。结论:血清INHB水平可作为临床早期预测卵巢储备功能下降的指标之一。尽早给予合理的性激素治疗可使卵巢功能得到改善,提高妊娠率。     

Exposure to polybrominated diphenyl ethers and male reproductive function in Greenland,Poland and Ukraine

Animal and a few human studies suggest that polybrominated diphenyl ethers (PBDEs) may affect male reproductive function. The aim of the present study was to evaluate if male reproductive function was associated with serum level of PBDEs. We evaluated, in a cross-sectional study, the effects of environmental exposure to BDE-47 and BDE-153 on reproductive hormones and semen quality, including markers of DNA damage and apoptosis, in 299 spouses of pregnant women from Greenland, Poland and Ukraine. Adjusted linear regression models indicated no strong associations between BDE-47 or BDE-153 exposure and markers of male semen quality or reproductive hormones. In the largest study to date we demonstrate that BDE-47 and BDE-153 exposure was not associated with altered semen characteristics or reproductive hormones, indicating that male reproductive function is not affected by the exposure level of these compounds in fertile European or Arctic populations.     

Association of inhibin α gene promoter polymorphisms with risk of idiopathic primary ovarian insufficiency in Korean women

ObjectiveThe aim of this study was to investigate whether two polymorphisms in the promoter region of inhibin alpha (INHA) are associated with risk of idiopathic primary ovarian insufficiency (POI) in Korean women, which is a controversial topic.Study designWe genotyped the INHA polymorphisms c.-16C > T (rs35118453) and c.-124A > G (rs11893842) of 136 POI patients and 225 controls in Korean women by polymerase chain reaction and restriction fragment length polymorphism analysis. We then compared differences in genotype and allele frequencies (AF) of the polymorphisms between the two groups to determine odds ratios (OR) and 95% confidence intervals (CI) as measures of the strength of association between genotype and POI.ResultsThere were no significant differences in genotype or AF of the polymorphisms between the POI patients and controls. Haplotype analysis revealed that the T–G haplotype of the two variant alleles was more frequent in POI patients than in the controls (OR = 1.630, 95% CI = 1.081–2.457). Combination genotype analysis showed that the CT + TT/GG genotype frequency was higher in POI patients than in the controls (OR = 2.414, 95% CI = 1.190–4.895).ConclusionsWe provide evidence to suggest that when the two variant alleles are combined, the c.-16C > T and c.-124A > G polymorphisms are associated with increased POI risk in Korean women. We postulate that interactions between the INHA polymorphisms may affect POI risk.     

抑制素/激活素与肾上腺皮质肿瘤

研究显示,组成抑制素/激活素的亚单位α、βA、βB在正常肾上腺皮质有表达,在肾上腺皮质肿瘤中亦有表达。抑制素α亚单位基因突变与肾上腺皮质肿瘤有关。对抑制素基因敲除小鼠的研究显示,激活素可能是肾上腺皮质肿瘤发生的抑制因子,故认为它们可能与肾上腺皮质肿瘤的发生有关。抑制素、激活素通过影响类固醇生成及细胞凋亡,与骨形态生成蛋白相互作用调节醛固酮的生成,从而参与肾上腺皮质肿瘤的发生。抑制素与Calretinin合用可鉴别肾上腺皮质肿瘤与嗜铬细胞瘤,抗抑制素α亚单位抗体也可鉴别肾上腺皮质肿瘤与肾细胞癌。     

Evidence for a role of the Leydig cells in control of the intratesticular secretion of inhibin

Injection of adult male rats with human chorionic gonadotrophin (hCG) caused a dose- and time-dependent increase in the levels of immunoactive inhibin in testicular interstitial fluid (IF), which differed from the pattern of change in testosterone levels. Blockage of the hCG-induced increase in IF levels of testosterone, by administration of aminoglutethimide, only partially attenuated the increase in levels of inhibin. Inhibin levels in IF were only increased by doses of hCG which cause inflammatory changes and focal seminiferous tubule damage, but there was no association between the degree of tubule damage and inhibin levels. It is concluded that one or more luteinizing hormone (LH)-regulated, non-steroidogenic Leydig cell products may be involved in the paracrine control of inhibin secretion. These data are of clinical relevance and of potential physiological significance.     

抑制素与妇女围绝经期综合征

抑制素是一种糖蛋白激素,在妇女主要由卵巢产生,它可以调节促卵泡生成素分泌。文章综述了抑制素的生理功能,与妇女围绝经期综合征发病机理的关系,对妇女围绝经期分期的影响,以及中医药治疗围绝经期综合征对抑制素的调节作用的研究概况。     

Regulation of Sertoli cell activin A and inhibin B by tumour necrosis factor α and interleukin 1α: interaction with follicle-stimulating hormone/adenosine 3',5'-cyclic phosphate signalling

Regulation of crucial events during spermatogenesis involves dynamic changes in cytokine production and interactions across the cycle of the seminiferous epithelium. Regulation of activin A and inhibin B production by the inflammatory cytokines, tumour necrosis factor α (TNFα) and interleukin 1α (IL1α), alone and in conjunction with FSH or a cAMP analogue (dibutyryl cAMP), was examined in cultures of Sertoli cells from 20-day old rats. Both TNFα and IL1α stimulated activin A secretion and expression of its subunit (β(A)) mRNA, and suppressed inhibin B secretion and expression of its subunit (α and β(B)) mRNAs. The actions of TNFα and IL1α were opposed by FSH and dibutyryl cAMP. Both cytokines inhibited FSH/dibutyryl cAMP-stimulated inhibin B secretion and mRNA expression as well as stem cell factor mRNA expression. Both cytokines also inhibited FSH-induced cAMP production, and reduced baseline FSH receptor mRNA expression. These data highlight the reciprocal relationship that exists between FSH/cAMP signalling and inflammatory cytokine signalling pathways in the control of Sertoli cell function, and production of activin A/inhibin B in particular. It is anticipated that these interactions play important roles in the fine control of events during the cycle of the seminiferous epithelium and in the inhibition of spermatogenesis during inflammation.     

Inhibins, activins, their binding proteins and receptors: Interactions underlying paracrine activity in the testis

The inhibin-related peptides are present in the testis from early gestation through adulthood. They are produced from multiple testicular sites in a highly regulated manner, suggesting important paracrine roles. Similarly, receptors for these peptides are located in specific stages of the seminiferous tubule and on particular cell types, and an additional level of control is afforded by specific binding proteins, such as follistatin, which may regulate bioavailability. The actions of these factors include the modulation of interstitial cell function and the increase of spermatogonial proliferation in vitro. It thus appears that activin and inhibin are significant factors in the local control of testicular funtion.     

Tibolone: a compound with tissue specific inhibitory effects on sulfatase

While many transforming growth factor-β (TGFβ) superfamily ligands such as TGFβ, activin, and the bone morphogenic proteins (BMPs) are critical to the control of growth, differentiation, and cell fate, inhibin has a more limited role and is primarily responsible for the regulation of one hormone from one cell-type in the anterior pituitary. Inhibin is an endocrine hormone, produced by the gonads, that inhibits follicle stimulating hormone (FSH) release from the pituitary gonadotrope. The other hormones in the superfamily do not appear to act in an endocrine fashion, but rather control cell function in a paracrine or autocrine manner. Many components of the TGFβ/activin/BMP signal transduction pathway have been elegantly defined; however, the mechanism of inhibin action has not been completely dissected. Several cell surface proteins that associate with inhibin have been identified recently, and these molecules may provide the clues necessary to understand how inhibin regulates reproductive function.