Vitamin E modulates androgen receptor gene expression to attenuate ovarian dysfunctions in a rat model of dehydroepiandrosterone-induced polycystic ovary

Objective:To investigate the protective effect of vitamin E in dehydroepiandrosterone(DHEA)-induced polycystic ovary in rats.Methods:Premature female Wistar rats were randomly allocated into four groups,with 7 rats in each group.Group栺received corn oil(vehicle)and served as the control group;group栻received 0.2 mL of 0.06 mg/g DHEA in corn oil;group栿received 200 mg/kg vitamin E;group桇received DHEA plus vitamin E.All treatments lasted for 15 days,with DHEA administered subcutaneously,while vitamin E and corn oil were administered orally.After the experiment,serum samples and ovaries were harvested for biochemical,immunohistochemical,hormonal,and histological analysis.The ovarian mRNA expression of androgen receptor was analyzed by reverse transcriptase quantitative polymerase chain reaction(qPCR).Results:The antioxidant and metabolic enzyme activity significantly decreased in the DHEA-treated rats compared to the control rats(P<0.05).Administration of vitamin E to DHEAtreated rats significantly decreased cytokines and malondialdehyde compared to the DHEA-treated rats.The histological analysis showed reduced atretic and cystic ovaries,increased E-cadherin and Bcl-2 expression,and reduced expression of Bax in the DHEAtreated rats co-treated with vitamin E.The mRNA expression of androgen receptor was upregulated in the DHEA-treated rats compared to the control rats.Conclusions:Vitamin E ameliorates the hyperandrogenic effect of DHEA-induced polycystic ovaries via metabolic,antioxidant,and anti-apoptotic pathways.

Characterization and functions of beta defensins in the epididymis

The epididymal β-defensins have evolved by repeated gene duplication and divergence to encode a family of proteins that provide direct protection against pathogens and also support the male reproductive tract in its primary function. Male tract defensins also facilitate recovery from pathogen attack. The β-defensins possess ancient conserved sequence and structural features widespread in multi-cellular organisms, suggesting fundamental roles in species survival. Primate SPAG11, the functional fusion of two ancestrally independent β-defensin genes, produces a large family of alternatively spliced transcripts that are expressed according to tissue-specific and species-specific constraints. The complexity of SPAG11 varies in different branches of mammalian evolution. Interactions of human SPAG11D with host proteins indicate involvement in multiple signaling pathways. （Asian J Andro12007 July; 9： 453- 462）

Prevalent false positives of azoospermia factor a （AZFa） microdeletions caused by single-nucleotide polymorphism rs72609647 in the sY84 screening of male infertility

Multiplex polymerase chain reaction （PCR） has been widely used to detect Y-chromosome micredeletions, which is one of the major causes of male infertility. Both the European Academy of Andrology （EAA） and the European Molecular Genetics Quality Network （EMQN） have recommended the use of sY84 and sY86 markers for the detection of azoospermia factor a （AZFa） microdeletion during DNA testing for male infertility. In this study, a large-scale analysis of AZF microdeletion in a total of 630 Chinese males, including healthy semen donors （n=200）, infertile males with normal sperm count （n=226） and patients with either nonobstructive azoospermia or severe oligozoospermia （n=204）, was performed. A series of nine sequence-tagged site （STS） markers from the AZF region of the Y chromosome was used to detect microdeletions. All primers were designed based on the recommendations of the National Center for Biotechnology Information. An unusually high incidence （73/630, 11.6%） of sY84-absent but sY86-present genotypes was observed in the AZFa microdeletion screening. Sequencing the sY84-flanking region revealed a total of 73 patients with sY84-absent but sY86-present genotypes have a T-to-G transversion at the fifth base from the 5＇ end of the reverse sY84 primer. These prevalent false positives, which were not only observed in infertile men, but also observed in donors, resulted from a single-nucleotide polymorphism （SNP） named rs72609647 in the targeting sequence of the reverse sY84 primer. Our study suggests that a pre-screening of existence of rs72609647 polymorphism can prevent the frequent false positive results of AZFa microdeletions detection in the infertile Chinese males. Given the SNP rs72609647 was recently found in a deep sequencing of a Chinese individual, the current EAA and EMQN standards may need to be scrutinized among different populations to avoid the potential genetic variations in the primer binding sequences.

Rat recombinant β-defensin 22 is a heparin-binding protein with antimicrobial activity

Approximately 40-50 β-defensins are predominantly expressed in the male reproductive system of mammals. This selective expression raises the question as to the roles of these molecules in innate immunity and fertility in the male reproductive tract. Rat β-defensin 22 is an epididymis-specific β-defensin expressed in segments 12-14 of the epididymis. This protein contains both β-defensin and lectin signature sequences, yet its antimicrobial activity and carbohydrate-binding ability have not been shown. We herein demonstrated the antimicrobial activity of recombinant rat β-defensin 22 against Escherichia coliand Candida albicans. Its lectinJike activity was also investigated by demonstrating its binding ability with heparin beads. This heparin-binding activity implies some potential roles for this defensin in determining the fertilisation capabilities of sperm.

Adansonia digitata aqueous leaf extract ameliorates dexamethasone-induced testicular injury in male Wistar rats

Objective:To evaluate the effects of aqueous leaf extract of Adansonia(A.)digitata L on dexamethasone-induced testicular damage in male Wistar rats.Methods:Twenty adult male Wistar rats weighing 170-190 g were divided into four groups.GroupⅠreceived 0.5 mL of phosphate buffer orally for 28 days and served as the normal control group;groupⅡreceived 10 mg/kg of dexamethasone(a synthetic glucocorticoid)intraperitoneally for 7 days and 0.5 mL of phosphate buffer orally for 21 days,groupⅢreceived 10 mg/kg of dexamethasone for 7 days and 800 mg/kg of A.digitata extract orally for 21 days;groupⅣreceived 10 mg/kg of dexamethasone for 7 days and 300 mg/kg of vitamin-E orally for 21 days.Dexamethasone was administered intra-peritoneally for 7 days and all administration lasted for 28 days.The rats were sacrificed by anesthesia with diethyl ether and the testes of each animal were harvested.The testis was homogenized in 0.25 M sucrose at 4℃for biochemical and histological analyses.Results:Administration of dexamethasone significantly decreased body weight,glucose-6-phosphate dehydrogenase(G6PDH),lactate dehydrogenase(LDH),superoxide dismutase(SOD),and glutathione peroxidase(GPx)(P<0.05),and significantly increased malondialdehyde(MDA)activities(P<0.05).The degeneration in the population of spermatogonia and vacuolation and abnormal widening of the interstitial spaces were observed in the rats treated with dexamethasone.However,administration of A.digitata significantly increased SOD,GPx,G6PDH,and LDH levels,significantly decreased MDA activities and improved the histoarchitecture of the testis(P<0.05).Conclusions:A.digitata may have an ameliorative effect on dexamethasone-induced testicular damage in Wistar rats because of its anti-inflammatory and antioxidant properties.

More evidence intratumoral DHT synthesis drives castration-resistant prostate cancer

Again-of-function stabilizing somatic mutation in 3β-hydroxysteroiddehydrogenase type 1 （3βHSDI, HSD3B1） was reported in castration-resistant prostate cancer. The A-C nucleotide polymorphism replaced asparagine-367 with threonine （3βHSD1-N367T） as a homozygous somatic mutation in a subset of castration-resistant prostate cancers by loss of heterozygosity of the wild-type allele. Increased stability of 3[HSD I-N367T was associated with decreased ubiquitin-mediated degradation and higher levels of dihydrotestosterone （DHT）. The studies suggest that genetic instability in castration-resistant prostate cancer favors the more stable 313HSD I-N367T mutant that contributes to drug resistance. A somatic mutation in a steroid metabolic enzyme required for DHT synthesis provides further support for intratumoral androgen synthesis contributing to prostate cancer progression.