Conserved roles of mouse DUX and human DUX4 in activating cleavage-stage genes and MERVL/HERVL retrotransposons.

To better understand transcriptional regulation during human oogenesis and preimplantation development, we defined stage-specific transcription, which highlighted the cleavage stage as being highly distinctive. Here, we present multiple lines of evidence that a eutherian-specific multicopy retrogene, DUX4, encodes a transcription factor that activates hundreds of endogenous genes (for example, ZSCAN4, KDM4E and PRAMEF-family genes) and retroviral elements (MERVL/HERVL family) that define the cleavage-specific transcriptional programs in humans and mice. Remarkably, mouse Dux expression is both necessary and sufficient to convert mouse embryonic stem cells (mESCs) into 2-cell-embryo-like ('2C-like') cells, measured here by the reactivation of '2C' genes and repeat elements, the loss of POU5F1 (also known as OCT4) protein and chromocenters, and the conversion of the chromatin landscape (as assessed by transposase-accessible chromatin using sequencing (ATAC-seq)) to a state strongly resembling that of mouse 2C embryos. Thus, we propose mouse DUX and human DUX4 as major drivers of the cleavage or 2C state.

Reproductive considerations in the setting of chronic viral illness.

Special considerations must be taken when patients with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C desire to become pregnant. Patients with chronic viral illnesses desire to have children at rates similar to the general population, and options are available to decrease both vertical transmission and viral transmission between partners. Preconception counseling or consultation with fertility specialists is imperative in patients with HIV, hepatitis B, and hepatitis C so that reproductive goals can be addressed and optimized. In couples in which one partner has HIV, the use of highly active antiretroviral therapy or preexposure prophylaxis can significantly reduce the risk of transmission between serodiscordant partners. The use of density gradient sperm-washing techniques and intrauterine insemination or in vitro fertilization results in an apparent lack of transmission of HIV between partners when the male partner is HIV-positive. Vertical transmission of HIV from mother to child can be reduced by use of highly active antiretroviral therapy regimens throughout pregnancy or by cesarean delivery in the setting of high maternal viral load. Transmission of hepatitis B between partners can be eliminated by vaccinating the uninfected partner. Vertical transmission from a hepatitis B-infected mother to a child can be reduced by vaccinating neonates with the standard hepatitis B vaccine series as well as hepatitis B immune globulin. Recent data have shown the antiviral medication tenofovir to be an effective way to reduce vertical transmission in the setting of high maternal viral load or the presence of hepatitis B e antigen. There are multiple antiviral medications available to treat chronic hepatitis C, although access to these medications often is limited by cost. Similar to HIV-positive patients, in settings in which the male partner is infected with hepatitis C, density gradient sperm washing can be used before intrauterine insemination or in vitro fertilization to reduce transmission of hepatitis C between partners. No safe and effective method exists to reduce vertical transmission of hepatitis C once a woman becomes pregnant, highlighting the importance of treatment of hepatitis C before pregnancy.

Sperm concentration is poorly associated with hypoandrogenism in infertile men.

OBJECTIVE: To evaluate the utility of routine hormone evaluation in all men presenting for infertility by understanding the relationship between sperm concentration and hypoandrogenism. METHODS: We performed a retrospective cross-sectional study between September 2013 and May 2014 at a tertiary referral center in Utah. Ninety-four men presenting for infertility consecutively between the ages of 18 and 55 years were identified. Our primary outcome was rate of hypoandrogenism among infertile men defined as the baseline total serum testosterone levels <300 ng/dL or bioavailable testosterone (BAT) levels <155 ng/dL. Secondary outcomes included association of normospermia, oligozoospermia, or azoospermia with biochemical or clinical hypoandrogenism. RESULTS: Thirty-nine men (41%) had a total serum testosterone level of <300 ng/dL, and 41 men (43%) had a BAT level <155 ng/dL. Biochemical and symptomatic hypoandrogenism was common; 17 men (18%) had a total testosterone level <300 ng/dL and ≥ 3 positive Androgen Deficiency in Aging Male (ADAM) responses, and 18 men (19%) had a BAT level of <155 ng/dL and ≥ 3 positive ADAM responses. Sperm concentration (normospermia, oligozoospermia, and azoospermia) was not associated with biochemical hypoandrogenism (total testosterone level <300 ng/dL or BAT level <155 ng/dL), symptomatic hypoandrogenism (≥ 3 positive ADAM responses), or sexual dysfunction (Sexual Health Inventory for Men score <21). CONCLUSION: Hypoandrogenism is common among infertile men, and routine hormonal evaluation may identify hypoandrogenism in many infertile men with otherwise normal semen analysis. Sperm concentration (normospermia, oligozoospermia, and azoospermia) is not well associated with hypoandrogenism in infertile men.