ADF/cofilin and actin dynamics in disease

ADF/cofilins are key regulators of actin dynamics in normal cells. Recent findings suggest that, under cellular stress, the wild-type proteins might form complexes with actin that can alter cell function. Owing to their rapid formation, these complexes might initiate or aid in the progression of diseases as diverse as Alzheimer's disease and ischemic kidney disease. Although evidence for their involvement in diseases other than Alzheimer's and ischemic kidney disease is tenuous, recent studies suggest that altered production, regulation or localization of these proteins might lead to cognitive impairment, inflammation, infertility, immune deficiencies and other pathophysiological defects.     

A family of human Y chromosomes has dispersed throughout northern Eurasia despite a 1.8-Mb deletion in the azoospermia factor c region

The human Y chromosome is replete with amplicons-very large, nearly identical repeats-which render it susceptible to interstitial deletions that often cause spermatogenic failure. Here we describe a recurrent, 1.8-Mb deletion that removes half of the azoospermia factor c (AZFc) region, including 12 members of eight testis-specific gene families. We show that this "b2/b3" deletion arose at least four times in human history-likely on inverted variants of the AZFc region that we find exist as common polymorphisms. We observed the b2/b3 deletion primarily in one family of closely related Y chromosomes-branch N in the Y-chromosome genealogy-in which all chromosomes carried the deletion. This branch is known to be widely distributed in northern Eurasia, accounts for the majority of Y chromosomes in some populations, and appears to be several thousand years old. The population-genetic success of the b2/b3 deletion is surprising, (i) because it removes half of AZFc and (ii) because the gr/gr deletion, which removes a similar set of testis-specific genes, predisposes to spermatogenic failure. Our present findings suggest either that the b2/b3 deletion has at most a modest effect on fitness or that, within branch N, its effect has been counterbalanced by another genetic, possibly Y-linked, factor.     

Sperm centriole assessment identifies male factor infertility in couples with unexplained infertility – a pilot study

Unexplained infertility affects about one-third of infertile couples and is defined as the failure to identify the cause of infertility despite extensive evaluation of the male and female partners. Therefore, there is a need for a multiparametric approach to study sperm function. Recently, we developed a Fluorescence-Based Ratiometric Analysis of Sperm Centrioles (FRAC) assay to determine sperm centriole quality. Here, we perform a pilot study of sperm from 10 fertile men and 10 men in couples with unexplained infertility, using three centriolar biomarkers measured at three sperm locations from two sperm fractions, representing high and low sperm quality. We found that FRAC can identify men from couples with unexplained infertility as the likely source of infertility. Higher quality fractions from 10 fertile individuals were the reference population. All 180 studied FRAC values in the 10 fertile individuals fell within the reference population range. Eleven of the 180 studied FRAC values in the 10 infertile patients were outliers beyond the 95% confidence intervals (P = 0.0008). Three men with unexplained infertility had outlier FRAC values in their higher quality sperm fraction, while four had outlier FRAC values in their lower quality sperm fraction (3/10 and 4/10, P = 0.060 and P = 0.025, respectively), suggesting that these four individuals are infertile due, in part, to centriolar defects. We propose that a larger scale study should be performed to determine the ability of FRAC to identify male factor infertility and its potential contribution to sperm multiparametric analysis.     

Proteomic analysis of N‐glycosylation of human seminal plasma

Seminal plasma is a mixture of secretions from several male accessory glands. The seminal plasma contains many secreted proteins which are important for sperm function and male fertility. In this study, we employed N‐linked glycosylated peptide enrichment, combined with LC–MS/MS analysis, and establish the first large scale N‐linked glycoproteome of human seminal plasma. Combined with the results of five biological replicates, a total of 720 N‐glycosylated sites on 372 proteins were identified. Analysis of variations among five individuals revealed similar compositions of N‐glycosylated proteins in seminal plasma. The N‐linked glycoproteome could help us understanding the biological functions of human seminal plasma. The data set could also be a resource for further screening of biomarkers for male diseases including cancer and infertility at the level of N‐glycosylation. For example, N‐glycosylated prostate‐specific antigen is known to be an efficient biomarker that can distinguish benign prostate hyperplasia from prostate cancer. All MS data have been deposited in the ProteomeXchange with identifier PXD000959 ( http://proteomecentral.proteomexchange.org/dataset/PXD000959 ).     

宫腔镜联合腹腔镜在女性不孕症诊治中的应用

目的：探讨宫腔镜联合腹腔镜在女性不孕诊断及治疗中的临床应用价值。方法：回顾性分析60例我院收治的采用宫腔镜联合腹腔镜进行诊断和治疗的女性不孕症患者为研究对象,对其临床资料进行分析。结果：宫腔镜联合腹腔镜检查发现,60例不孕症患者中,56．7％的患者患有慢性盆腔炎,16．7％的患者为子宫内膜异位症,11．7％的患者为多囊卵巢综合征;单纯腹腔镜检查的阳性检出率为60．0％,单纯宫腔镜检查的阳性检出率为28．3％,宫腔镜联合腹腔镜检查的阳性检出率高达91．7％,宫腔镜联合腹腔镜镜栓阳性发现率明显高于前二者（P〈0．05）。治疗前,双侧不通、一侧通畅和双侧输卵管通畅的患者分别为38．3％、48．3％和13．3％,经宫腔镜联合腹腔镜治疗后分别为11．7％、50．o％和38．3％,差异均有统计学意义（P〈0．05）。34例原发性不孕患者,术后13例妊娠,妊娠率38．2％;26例继发性不孕患者,术后15例妊娠,妊娠率57．7％;总妊娠率为46．7％,其中宫外孕2例。结论：宫腔镜联合腹腔镜检查可帮助明确女性不孕症患者明确原因及发病部位,并可针对病因进行治疗,提高女性不孕症的病因诊断准确率及治愈率。     

Evaluation of testicular dose and associated risk from common pelvis radiation therapy in Iran

This study aimed to investigate testicular dose (TD) and the associated risk of heritable disease from common pelvis radiotherapy of male patients in Iran. In this work, the relation between TD and changes in beam energy, pelvis size, source to skin distance (SSD) and beam directions (anterior or posterior) was also evaluated. The values of TDs were measured on 67 randomly selected male patients during common pelvis radiotherapy using 1.17 and 1.33 MeV, Theratron Cobalt-60 unit at SSD of 80 cm and 9 MV, Neptun 10 PC and 18 MV, GE Saturne 20 at SSD of 100 cm at Seyed-Al Shohada Hospital, Isfahan, Iran. Results showed that, the maximum TD was up to 12% of the tumor dose. Considering the risk factor for radiation-induced heritable disorders of 0.1% per Sv, an excess risk of hereditary disorders of 72 per 10,000 births was conservatively calculated. There was a significant difference in the measured TD using different treatment machines and energies (P < 0.001). The Pearson Correlation test showed that, as expected, there was a correlation between TD and patient's pelvis size (r = 0.275, P < 0.001). Using the student's t-tests, it was found that, there was not a significant difference between TD and beam direction (P = 0.231). Iranian male patients undergoing pelvic radiotherapy have the potential of receiving a TD of more than 1 Gy which might result in temporary azoospermia. The risk for induction of hereditary disorders in future generations should be considered as low but not negligible in comparison with the correspondent nominal risk.     

Mitochondria: Participation to infertility as source of energy and cause of senescence

Mitochondria is a powerhouse organelle involved in ATP synthesis, calcium signaling, reactive oxygen species (ROS) by oxidative stress production, cell cycle arrest via apoptosis and sex steroid hormones biosynthesis. Improvement of sperm parameters such as motility, capacitation, acrosome reaction, and oocyte interaction, involve regulation of ROS levels by the mitochondria. In human, the relation between the quantitative level of mitochondrial DNA (mtDNA), oocyte cytoplasm maturation and fertilization potential, is not clear. It has been hypothesized that oocytes without sufficient wild type mtDNA and therefore able to generate ATP, would not normally be ovulated. This is reflected in the low numbers of mtDNA observed in degenerate oocytes obtained through super ovulation protocols during assisted reproductive technology programs. Different theories place mitochondria in a central role of oxidative damage to cells and tissues related to infertility declining and aging. Mitochondria-dependent apoptosis seems to be responsible for the pre and post-natal decline in germ cells, embryo development, implantation failure, and miscarriages.     

多囊卵巢综合征不孕患者性激素水平与免疫失衡及胰岛素抵抗指数的关系研究

摘要 目的：探讨多囊卵巢综合征（PCOS）不孕患者性激素水平与免疫失衡及胰岛素抵抗指数的关系。方法：选取2019年1月～2021年12月于山东中医药大学附属医院就诊的88例PCOS不孕患者作为研究组,同期选取健康体检女性80例作为对照组。检测比较两组的性激素、Th1/Th2免疫相关指标以及稳态模型胰岛素抵抗指数（HOMA-IR）,采用Pearson相关系数分析PCOS不孕患者性激素与Th1/Th2、HOMA-IR的相关性。结果：研究组的血清黄体生成素（LH）、雌二醇（E₂）、睾酮（T）水平及LH/FSH比值均明显高于对照组,而促卵泡激素（FSH）水平低于对照组（P＜0.05）。研究组的外周血干扰素-γ（IFN-γ）水平、Th1细胞比例及Th1/Th2比值均明显高于对照组（P＜0.05）,而两组间白细胞介素-4（IL-4）水平和Th2细胞比例无显著差异（P＞0.05）。研究组的空腹血糖（FPG）、空腹胰岛素（FINS）水平及HOMA-IR均明显高于对照组（P＜0.05）。Pearson相关性分析结果显示,PCOS不孕患者的E₂、T水平、LH/FSH比值与Th1/Th2比值、HOMA-IR均呈正相关（P＜0.05）。结论：PCOS不孕患者存在胰岛素抵抗及免疫失衡,且胰岛素抵抗、免疫失衡与其性激素表达有关。     

Effect of delivery season on subsequent birth interval in early 20th century in Japan

Questionnaires of birth dates of family members (13 404 families in total) were analyzed in order to examine the effects of delivery season of a baby on the subsequent birth interval. Deliveries at maternal age of 20–34 years were used. In 1921–1935, the mothers who had been delivered of a baby in August–October showed the shortest (30.62 months geometric mean) and those in February–April the longest (34.05 months) non-last intervals, with a highly significant difference among the four delivery seasons (P<0.001, Kruskal-Wallis test,n=5678). Although the intervals were abruptly prolonged just before the last birth, the above difference was also consistent in the last intervals. When seasonal distributions of last and non-last births were compared, last births tended to be concentrated in the summer half of a year (P<0.05) in 1921–1935. In 1951–1965, overall geometric mean of the interval shortened to 28.44 months, and the length of intervals did not differ appreciably according to the season of preceding delivery. Deliveries in late summer (August–October) in 1921–1935, therefore, were associated with increased risk of termination of reproduction, on one hand, but a lowered chance of prolongation of the subsequent interval, on the other hand. Possible environmental factors are discussed to explain this apparently paradoxical phenomenon.     

Ovarian parameters and fertility of dairy cows selected for one QTL located on BTA3

Recently, one Quantitative Trait Locus (QTL) of female fertility located on Bos Taurus chromosome 3 (BTA3), QTL-F-Fert-BTA3, has been identified in Holstein breed. It is implied in the success rate after the first AI (AI1) in cow. The failure of pregnancy can be due to several factors involved in the different steps of the reproductive process. The aim of our study was to finely phenotype heifers and primiparous cows selected for their haplotype at the QTL-F-Fert-BTA3. We specifically studied the ovarian follicular dynamic and several fertility parameters. Females carrying the favourable haplotype “fertil+” or unfavourable haplotype “fertil−” were monitored by transrectal ultrasonography during their cycle before the first AI (AI1). Follicular dynamic was similar between the two groups. However, the length of the estrus cycle was shorter in heifers than in primiparous cows and two-wave cycles were shorter than three-wave cycles, regardless of the age and the haplotype. The concentration of plasma anti-Müllerian hormone was correlated with the number of small antral follicles. It was higher in heifers than in primiparous cows, independently of their haplotype. The success rate at the AI1 was significantly higher in “fertil+” than in “fertil−” primiparous cows, 35 d after the AI1 (70% vs 39%). In both haplotypes, pregnancy failure occurred mainly before 21 d after AI1. The commencement of luteal activity after calving was significantly earlier in “fertil+” than in “fertil−” primiparous cows. Calving-AI1 and calving-calving intervals were similar between “fertil+” and “fertil−” primiparous cows. Taken together, “fertil+” and “fertil−” primiparous cows present a difference in the success rate after AI1 that is not explained by variations of ovarian dynamics.