A common mutation in the defensin DEFB126 causes impaired sperm function and subfertility.

A glycosylated polypeptide, β-defensin 126 (DEFB126), derived from the epididymis and adsorbed onto the sperm surface, has been implicated in immunoprotection and efficient movement of sperm in mucosal fluids of the female reproductive tract. Here, we report a sequence variant in DEFB126 that has a two-nucleotide deletion in the open reading frame, which generates an abnormal mRNA. The allele frequency of this variant sequence was high in both a European (0.

Serum inhibin-b in fertile men is strongly correlated with low but not high sperm counts: a coordinated study of 1,797 European and US men.

Objective: To describe associations between serum inhibin-b and sperm counts, adjusted for effect of time of blood sampling, in larger cohorts than have been previously reported.

Design: Cross-sectional studies of spermatogenesis markers.

Setting: Four European and four US centers.

Rhesus macaque blastocysts resulting from intracytoplasmic sperm injection of vacuum-dried spermatozoa.

Background: Sperm desiccation is an attractive approach for sperm preservation. In this study, we examined the feasibility and efficiency of intracytoplasmic sperm injection using vacuum-dried rhesus macaque sperm in CZB medium supplemented with 10% fetal bovine serum.

Methods: A total of 109 MII oocytes were injected with 69 fresh ejaculated sperm and 40 vacuum-dried sperm.

Semen quality in fertile men in relation to psychosocial stress.

Objective: To examine the association between stressful life events and semen parameters.

Design: Cross-sectional analysis in a pregnancy cohort study.

Setting: Prenatal clinics in five U.

Release of DEFB126 from macaque sperm and completion of capacitation are triggered by conditions that simulate periovulatory oviductal fluid.

Capacitation of macaque sperm in vitro has been achieved efficiently only with the addition of both cyclic nucleotides and methylxanthines. The use of these exogenous sperm activators clouds an understanding of the normal mechanisms underlying capacitation and may slow early embryo development following in vitro fertilization (IVF). We demonstrate that culture medium which simulates periovulatory oviductal fluid with respect to bicarbonate (HCO(3)(-)) and glucose concentration induces capacitation in a high percentage of macaque sperm as determined by the ability of sperm to undergo both the release of coating protein DEFB126 and the zona pellucida-induced acrosome reaction (AR).

Beta-defensin 22 is a major component of the mouse sperm glycocalyx.

Surface components of sperm isolated from the cauda epididymides were stabilized by whole sperm fixation for immunization of rabbits. The resulting immunoglobulins (Igs) recognized a single protein of 130 kDa (non-reduced) or 54-57 kDa (reduced) on western blots of cauda sperm. Igs recognized the same 54-57 kDa protein band on whole tissue blots of the corpus and cauda epididymidis and vas deferens.

Macaque sperm coating protein DEFB126 facilitates sperm penetration of cervical mucus.

Background: Sperm coating protein beta-defensin 126 (DEFB126) is adsorbed onto the entire surface of macaque sperm in the caudal epididymis and is retained on viable sperm collected from the cervix and the uterine lumen of mated female macaques. We investigated the role of sperm coating protein DEFB126 in cervical mucus penetration (CMP).

Methods: Cervical mucus (CM) was collected from peri-ovulatory female macaques and loaded into CMP chambers.

Beta-defensin 126 on the surface of macaque sperm mediates attachment of sperm to oviductal epithelia.

Beta-defensin 126 (DEFB126) coats the entire surface of macaque sperm until sperm become capacitated, and the removal of DEFB126 from over the head of sperm is required for sperm-zona recognition. Viable sperm collected from cervix and the uterine lumen of mated female macaques had DEFB126 coating the entire surface, suggesting that DEFB126 is retained on sperm en route to the oviduct. DEFB126 plays a major role in attachment of sperm to oviductal epithelial cells (OECs).

Hourly human chorionic gonadotropin secretion profiles during the peri-implantation period of successful pregnancies.

Objective: To characterize the hourly profiles of hCG secretion in blood during conceptive cycles that ended in successful pregnancy.

Design: Prospective study.

Setting: University fertility clinic and research laboratories.

Damage to chromosomes and DNA of rhesus monkey sperm following cryopreservation.

Fresh and frozen-thawed rhesus monkey sperm were analyzed for DNA damage using the comet assay and for chromosome damage by cytogenetic analysis after intracytoplasmic sperm injection (ICSI) into mouse oocytes. The percentage of fresh sperm with damaged DNA in ejaculated semen was 0 to 2.7% (n = 5).

Hyperactivation of monkey spermatozoa is triggered by Ca2+ and completed by cAMP.

Digital image analysis of the flagellar movements of cynomolgus macaque spermatozoa hyperactivated by caffeine and cAMP was carried out to understand the change in flagellar movements during hyperactivation. The degree of flagellar bending increased remarkably after hyperactivation, especially at the base of the midpiece. Mainly two beating patterns were seen in the hyperactivated monkey sperm flagella: remarkably asymmetrical flagellar bends of large amplitude and relatively symmetrical flagellar bends of large amplitude.

Semen and sperm reference ranges for men 45 years of age and older.

The most widely used reference values for human semen and sperm variables were developed by the World Health Organization (WHO) to help assess the fertility status of men interested in reproduction (typically a younger population). In this retrospective analysis, data from a large population of men aged 45 years or older were analyzed to derive semen and sperm reference ranges for an older population. Baseline semen samples were obtained from 1174 men with no or mild erectile dysfunction (ED) during the screening phase of two clinical trials evaluating the effects of a drug on human spermatogenesis.

Beta-defensin 126 on the cell surface protects sperm from immunorecognition and binding of anti-sperm antibodies.

Beta-defensin 126 (DEFB126), formerly known as epididymal secretory protein 13.2 (ESP13.2), coats the entire primate sperm surface until completion of capacitation, and it is a candidate for providing immune protection in the female reproductive tract.

Secretion and excretion of human chorionic gonadotropin during early pregnancy.

Objective: To characterize the profiles of human chorionic gonadotropin (hCG) secretion in blood and its subsequent excretion in urine during conceptive cycles that ended in successful pregnancy and in spontaneous abortion.

Design: A prospective study.

Setting: University fertility clinic and research laboratories.

Effect of environmental tobacco smoke on levels of urinary hormone markers.

Our recent study showed a dose-response relationship between environmental tobacco smoke (ETS) and the risk of early pregnancy loss. Smoking is known to affect female reproductive hormones. We explored whether ETS affects reproductive hormone profiles as characterized by urinary pregnanediol-3-glucuronide (PdG) and estrone conjugate (E1C) levels.

Macaque sperm release ESP13.2 and PSP94 during capacitation: the absence of ESP13.2 is linked to sperm-zona recognition and binding.

ESP13.2 coats the entire surface of macaque sperm and remains until sperm become capacitated (Yudin et al., 2003: Biol Reprod 69: 1118-1128).

Quality control of laboratory methods for semen evaluation in a multicenter research study.

Rigorously standardized laboratory protocols and strict quality control (QC) are essential for meaningful comparisons between semen quality data from multiple sites. We describe our experience with the Study for Future Families (SFF), a multicenter study of semen quality in the United States. Detailed protocols were developed, and technicians from each study site attended a training session at the central laboratory.

Standardized methods for semen evaluation in a multicenter research study.

Semen evaluation methodology is complex and difficult to standardize. Rigorously standardized laboratory protocols and strict quality control (QC) are essential for meaningful comparison of data from multiple sites. We describe the methods used for determination of semen volume, sperm concentration, and percent sperm motility in the Study for Future Families, a multicenter study of semen quality in the United States.

Paternal smoking and pregnancy loss: a prospective study using a biomarker of pregnancy.

Results of studies on paternal smoking and spontaneous abortions have been inconsistent. The authors examined the effect of paternal smoking on the risk of pregnancy loss in a prospective cohort of 526 newly married, nonsmoking, female textile workers in China between 1996 and 1998. Upon stopping contraception, subjects provided daily urine specimens and records of vaginal bleeding for up to 1 year or until clinical pregnancy.

The relationship between environmental exposure to phthalates and computer-aided sperm analysis motion parameters.

The general population is exposed to phthalates through consumer products, diet, and medical devices. The present study explored whether phthalates, reproductive toxins in laboratory animals, were associated with altered sperm movement characteristics in men. Two-hundred twenty subjects provided a semen sample for computer-aided sperm analysis (CASA) and a urine sample for measurement of phthalate monoesters, monoethyl (MEP), monobenzyl (MBzP), mono-n-butyl (MBP), mono-2-ethylhexyl (MEHP), and monomethyl (MMP).

Bromodichloromethane inhibits human placental trophoblast differentiation.

Epidemiological data suggest an association between exposures to bromodichloromethane (BDCM), a trihalomethane found in drinking water as a result of drinking water disinfection, and an increased risk of spontaneous abortion. We previously hypothesized that BDCM targets the placenta and showed that the secretion of chorionic gonadotrophin (CG) was reduced in primary cultures of human term syncytiotrophoblasts exposed to BDCM. In the present study we extend this observation by evaluating the effects of BDCM on the morphological differentiation of mononucleated cytotrophoblast cells to multinucleated syncytiotrophoblast-like colonies.

Trihalomethane levels in home tap water and semen quality.

Background: Trihalomethanes (THMs) are byproducts of drinking water chlorination whose effects on semen quality have not been previously studied in humans.

Methods: We examined the relationship of THMs to semen quality in 157 healthy men from couples without known risk factors for infertility. Total THM (TTHM) levels were assigned based on water utility measurements taken during the 90 days preceding semen collection.

Effect of bromodichloromethane on chorionic gonadotrophin secretion by human placental trophoblast cultures.

Bromodichloromethane (BDCM) is a trihalomethane found in drinking water as a by-product of disinfection processes. BDCM is hepatotoxic and nephrotoxic in rodents and has been reported to cause strain-specific full-litter resorption in F344 rats during the luteinizing hormone-dependent phase of pregnancy. In humans, epidemiological studies suggest an association between exposure to BDCM in drinking water and increased risk of spontaneous abortion.