The establishment and maintenance of spermatogenesis in mammals requires specialized networks of gene expression programs in the testis. The gonad-specific TAF4b component of TFIID (formerly TAF II 105) is a transcriptional regulator enriched in the mouse testis. Herein we show that TAF4b is required for maintenance of spermatogenesis in the mouse. While young Taf4b-null males are initially fertile, Taf4b-null males become infertile by 3 mo of age and eventually exhibit seminiferous tubules devoid of germ cells. At birth, testes of Taf4b-null males appear histologically normal; however, at post-natal day 3 gonocyte proliferation is impaired and expression of spermatogonial stem cell markers c-Ret, Plzf, and Stra8 is reduced. Together, these data indicate that TAF4b is required for the precise expression of gene products essential for germ cell proliferation and suggest that TAF4b may be required for the regulation of spermatogonial stem cell specification and proliferation that is obligatory for normal spermatogenic maintenance in the adult. Spermatogenesis is a complex process requiring the specialized function of multiple cell types including somatic and germ cells that collectively results in the continuous production of functional sperm in adult males. The unlimited production of male gametes is largely accomplished through the ability of spermatogonial stem cells to self-renew in the adult testis. These complex and multifaceted events are dependent on appropriate expression and action of specific genes at multiple stages of germ cell and testicular development (Matzuk and Lamb 2002;McLaren 2003). The precise temporal and spatial expression of specific transcription factors is also essential for proper execution of spermatogenesis (SassoneCorsi 1997). Emerging evidence now suggests that in addition to gonad-specific transcription factors, specialized components of the basal RNA Polymerase II machinery are also critical for the execution of gonad-specific programs of gene expression (Hochheimer and Tjian 2003).The TFIID complex is a core RNA polymerase complex that contains the TATA-binding protein (TBP) and 14 TBP-associated factors (TAFs) that function in core promoter recognition and activator-dependent RNA Polymerase II recruitment (Verrijzer and Tjian 1996). While most TFIID subunits are expressed and function broadly in most cell types, there are selective TFIID subunits that apparently have evolved to function in the specification of gonadal-specific programs of gene expression. In the mouse, TAF4b is a component of TFIID that is highly enriched in gonadal tissues and is required for ovarian follicle development (Freiman et al. 2001). TAF4b is similar in structure to its broadly expressed paralog TAF4 (TAF II 130). While TAF4 and TAF4b display overlapping expression patterns in certain cell types, TAF4b is essential for regulating the selective expression of ovarian-specific gene expression patterns required for female fertility (Freiman et al. 2001).Several other members of the basal transcription mac...

Seminal plasma is a fluid that originates from the testis, epididymis,prostate, and seminal vesicles, and hence, proteomic studies may identify potential markers of infertility and other diseases of the genito-urinary tract. We profiled the proteomes of pooled seminal plasma from fertile Control and post-vasectomy (PV) men. PV seminal plasma samples are void of proteins originating from the testis and the epididymis due to ligation of the vas deferens, and hence, comparative analysis of Control and PV data sets allows for identification of proteins originating from these tissues. Utilizing offline MudPIT and high-resolution mass spectrometry, we were able to identify over 2000 proteins in Control and PV pools each and over 2300 proteins all together. With semiquantitative analysis using spectral counting, we catalogued 32 proteins unique to Control, 49 at lower abundance in PV, 3 unique to PV, and 25 at higher abundance in PV. We believe that proteins unique to Control or at lower abundance in PV have their origin in the testis and the epididymis. Public databases have confirmed that many of these proteins originate from the testis and epididymis and are linked to the reproductive tract. These proteins may serve as candidate biomarkers for future studies of infertility and urogenital diseases.

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In one of the largest cohorts of male fertility and obesity, serum hormone and semen parameters demonstrated mild but significant relationships with BMI, possibly contributing to subfertility in this population.

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Infertility affects approximately 15% of couples with equivalent male and female contribution. Absence of sperm in semen, referred to as azoospermia, accounts for 5-20% of male infertility cases and can result from pretesticular azoospermia, non-obstructive azoospermia (NOA), and obstructive azoospermia (OA). The current clinical methods of differentiating NOA cases from OA ones are indeterminate and often require surgical intervention for a conclusive diagnosis. We catalogued 2048 proteins in seminal plasma from men presented with NOA. Using spectral-counting, we compared the NOA proteome to our previously published proteomes of fertile control men and postvasectomy (PV) men and identified proteins at differential abundance levels among these clinical groups. To verify spectral counting ratios for candidate proteins, extracted ion current (XIC) intensities were also used to calculate abundance ratios. The Pearson correlation coefficient between spectral counting and XIC ratios for the Control-NOA and NOA-PV data sets is 0.83 and 0.80, respectively. Proteins that showed inconsistent spectral counting and XIC ratios were removed from analysis. There are 34 proteins elevated in Control relative to NOA, 18 decreased in Control relative to NOA, 59 elevated in NOA relative to PV, and 16 decreased in NOA relative to PV. Many of these proteins have expression in the testis and the epididymis and are linked to fertility. Some of these proteins may be useful as noninvasive biomarkers in discriminating NOA cases from OA.

For men struggling to conceive with their partners, diagnostic tools are limited and often consist of only a standard semen analysis. This baseline test serves as a crude estimation of male fertility, leaving patients and clinicians in need of additional diagnostic biomarkers. Seminal fluid contains the highest concentration of molecules from the male reproductive glands, therefore, this review focuses on current and novel seminal biomarkers in certain male infertility scenarios, including natural fertility, differentiating azoospermia etiologies, and predicting assisted reproductive technique success. Currently available tests include antisperm antibody assays, DNA fragmentation index, sperm fluorescence in situ hybridization, and other historical sperm functional tests. The poor diagnostic ability of current assays has led to continued efforts to find more predictive biomarkers. Emerging research in the fields of genomics, epigenetics, proteomics, transcriptomics, and metabolomics holds promise for the development of novel male infertility biomarkers. Seminal protein-based assays of TEX101, ECM1, and ACRV1 are already available or under final development for clinical use. Additional panels of DNA, RNA, proteins, or metabolites are being explored as we attempt to understand the pathophysiologic processes of male infertility. Future ventures will need to continue data integration and validation for the development of clinically useful infertility biomarkers to aid in male infertility diagnosis, treatment, and counseling.

STUDY QUESTION: How knowledgeable are men about the medical, environmental and psychological factors that are associated with male infertility? SUMMARY ANSWER: Men, across most demographic groups, have limited knowledge of the various factors that are associated with male infertility.WHAT IS KNOWN ALREADY: Few surveys have focused on men's knowledge of their own fertility. Studies of both men and women have found that men are comparatively less knowledgeable about issues of fertility and reproductive health.STUDY DESIGN, SIZE, DURATION: A regionally representative sample of Canadian men completed a web-based survey of male fertility and reproductive health, over a 2-month period in 2015.PARTICIPANTS/MATERIALS, SETTING, METHODS: Men, aged 18-50 years, were recruited for the study. There were 701 male participants, with a mean age of 34.1 years. Each participant was asked to identify factors associated with male infertility; fertility knowledge was assessed through two open-ended questions and a comprehensive list of risk factors and attendant health issues.MAIN RESULTS AND THE ROLE OF CHANCE: Men were only able to identify 51% of the risk factors and 45% of the health issues associated with male infertility. Men were most aware of the modifiable risk factors for infertility (e.g. sexually transmitted infections, smoking cigarettes), relative to their knowledge of fixed risk factors (e.g. delayed puberty, size of testicles) and the attendant health issues (e.g. cardiovascular disease, diabetes). The overall level of fertility knowledge did not vary by most demographic characteristics (e.g. age, education, employment, income), though men from ethnic minority groups displayed moderately greater awareness. Additionally, younger men, those with lower incomes and those who had no desire to have future biological children were more likely to identify themselves as unaware of associations with infertility in the open-ended questions. Self-reported knowledge was significantly associated with higher overall knowledge scores. More than half of the sample expressed an interest in obtaining information about male fertility and reproductive health, with the majority of these men indicating that medical professionals and online sources were their preferred methods for receiving information. LIMITATIONS, REASONS FOR CAUTION:Participants were self-selected and required to have Internet access in order to participate. This may affect the generalizability of results. WIDER IMPLICATIONS OF THE FINDINGS:Previous studies of fertility knowledge have either omitted men from their samples or when men have been included, they were asked about general fertility or women's fertility. This is the first large-scale survey that focuses solely on men's knowledge of male fertility. Insight into the areas where men's knowledge may be lacking can inform strategies for © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: j...