Regulation of NHE3 subcellular localization in epididymal principal cells: pH, cyclic adenosine 3,5 monophosphate (cAMP), and adenosine signaling.

Introduction: The epididymis creates an optimal acidic luminal environment for sperm maturation and storage. In epididymal principal cells (PCs), proton secretion is activated by the accumulation of the sodium-proton exchanger type 3, NHE3 (SLC9A3), in apical stereocilia. PCs also secrete ATP, which is hydrolyzed into adenosine by ectonucleotidases.

Purinergic signaling in the male reproductive tract.

Purinergic receptors are ubiquitously expressed throughout the body and they participate in the autocrine and paracrine regulation of cell function during normal physiological and pathophysiological conditions. Extracellular nucleotides activate several types of plasma membrane purinergic receptors that form three distinct families: P1 receptors are activated by adenosine, P2X receptors are activated by ATP, and P2Y receptors are activated by nucleotides including ATP, ADP, UTP, UDP, and UDP-glucose. These specific pharmacological fingerprints and the distinct intracellular signaling pathways they trigger govern a large variety of cellular responses in an organ-specific manner.

Expression of the pro-inflammatory P2Y14 receptor in the non-vasectomized and vasectomized human epididymis.

Background: Vasectomy causes spermatozoa accumulation in the epididymis, which may cause epididymitis. Inflammation is triggered by alert molecules released following tissue stress or injury. These include uracil-diphosphate glucose (UDP)-glucose, which activates the pro-inflammatory P2Y14 receptor (P2Y14), and induces immune cell recruitment.

Differential gene expression profiles of human efferent ducts and proximal epididymis.

Background: Gene expression patterns along the epididymis are established by specific transcription factor networks that coordinate region-specific functions. In rodents, the epididymis can be divided in up to 19 segments. Based on gross anatomy, the human epididymis is divided into caput, corpus, and cauda segments together with efferent ducts that occupy the proximal part of this organ.

Impact of male fertility status on the transcriptome of the bovine epididymis.

Study Question: Can region-specific transcriptional profiling of the epididymis from fertile and sub-fertile bulls predict the etiology of fertility/sub-fertility in males?

Summary Answer: The highly regulated gene expression along the bovine epididymis is affected by the fertility status of bulls used for artificial insemination.

What Is Known Already: In mammals, sperm maturation and storage occur in the epididymis. Each epididymal segment has his own transcriptomic signature that modulates the intraluminal composition and consequently governs sequential modifications of the maturing male gamete.

Preclinical evaluation of a TEX101 protein ELISA test for the differential diagnosis of male infertility.

Background: TEX101 is a cell membrane protein exclusively expressed by testicular germ cells and shed into seminal plasma. We previously verified human TEX101 as a biomarker for the differential diagnosis of azoospermia, and developed a first-of-its-kind TEX101 ELISA. To demonstrate the clinical utility of TEX101, in this work we aimed at evaluating ELISA performance in a large population of fertile, subfertile, and infertile men.

Dicarbonyl L-xylulose reductase (DCXR), a "moonlighting protein" in the bovine epididymis.

During maturation and the acquisition of their fertilization potential, male germ cells are subjected to various sequential modifications that occur in the epididymis. Protein addition, reorganization or withdrawal, comprise some of these modifications. Dicarbonyl L-xylulose reductase (DCXR), a multifunctional protein involved in various enzymatic and protein interaction processes in different physiological systems, is one of the proteins added to spermatozoa in the epididymis.

Investigation of male infertility using quantitative comparative proteomics.

Male factors account for 40% of infertility cases. The identification of differentially expressed proteins on spermatozoa from fertile and infertile men can help in the elucidation of the molecular basis of male infertility. The aim of this study was to compare sperm proteomes from 3 different groups: fertile men, normozoospermic men consulting for infertility, and normozoospermic men with an impaired capacity for fertilization (IVF-failure).

Cysteine-rich secretory protein 1 in seminal plasma: potential biomarker for the distinction between obstructive and nonobstructive azoospermia.

Objective: To investigate the presence of cysteine-rich secretory protein 1 (CRISP1) in seminal plasma as a means of distinguishing between obstructive azoospermia (OA) and nonobstructive azoospermia (NOA).

Design: Seminal plasma from normospermic donors (n = 45) and azoospermic donors (n = 80) was examined to determine CRISP1 levels. Neutral alpha-glucosidase (NAG) enzymatic activity was measured for comparison with CRISP1 levels.

microRNA signature is altered in both human epididymis and seminal microvesicles following vasectomy.

Study Question: Does vasectomy impact microRNA (miRNA) expression in the epididymis and seminal microvesicles (SMVs) in a non-reversible manner?

Summary Answer: The miRNA signature in the epididymis and SMVs is altered by vasectomy and only partially restored after vasovasostomy surgery.

What Is Known Already: Vasectomy modifies the epididymal transcriptome and triggers non-reversible changes that affect sperm function. Some vasovasostomized men experience a reduced fertility outcome.

Role of microRNAs in controlling gene expression in different segments of the human epididymis.

Background: The molecular mechanisms implicated in regionalized gene expression in the human epididymis have not yet been fully elucidated. Interestingly, more than 200 microRNAs (miRNAs) have been identified in the human epididymis and could be involved in the regulation of mRNA stability and post-transcriptional expression in this organ.

Methods: Using a miRNA microarray approach, we investigated the correlation between miRNA signatures and gene expression profiles found in three distinct regions (caput, corpus and cauda) of human epididymides from 3 donors.

Gene expression in the epididymis of normal and vasectomized men: what can we learn about human sperm maturation?

Anatomically, the human epididymis is unusual when compared with the excurrent duct of other eutherian mammals. Furthermore, clinical observations suggest that it may not be as important for sperm maturation as is the case for laboratory animals. In contrast, hierarchical clustering of microarray data of epididymides from normal men revealed 2274 modulated qualifiers between the epididymal segments, 1184, 713, and 269 of them being highly expressed in the caput, corpus, and cauda, respectively.

Vasectomy affects cysteine-rich secretory protein expression along the human epididymis and its association with ejaculated spermatozoa following vasectomy surgical reversal.

The epididymis is essential for the acquisition of sperm fertilizing ability and forward motility. After vasectomy, the flux and composition of the epididymal fluid are modified, causing possible sequelae to the occluded excurrent duct. Some of these sequelae may not be reversible following vasovasostomy, affecting sperm physiology and their fertilizing ability.

Effects of vasectomy on gene expression profiling along the human epididymis.

Worldwide, almost 100 million men rely on vasectomy for male contraceptive purposes. Due to changes in their personal lives, an increasing number of these men request surgical vasectomy reversal. Unfortunately, a significant proportion of these men remain infertile, despite the reestablishment of patent ducts, possibly due to epididymal damage caused by vasectomy.

Epididymal P34H protein deficiency in men evaluated for infertility.

Our study aimed to compare the frequency of epididymal protein P34H deficiency in a population of men undergoing routine infertility evaluation with that in men with proven fertility. Our results suggest that a significant proportion of men investigated for male infertility may be epididymal protein P34H deficient.

HE1/NPC2 status in human reproductive tract and ejaculated spermatozoa: consequence of vasectomy.

We have previously demonstrated that the amount of HE1/NPC2 mRNA and protein expressed in the human epididymis is decreased under vasectomy. In this study, western blot analyses showed that many vasovasostomized men are characterized by high HE1/NPC2 levels in spermatozoa when compared with fertile donors. HE1/NPC2 association with sperm from vasovasostomized men was not related to low motility per se as spermatozoa from asthenospermic men have HE1/NPC2 levels similar to those in normal fertile semen samples.

Membranous and structural damage that occur during cryopreservation of human sperm may be time-related events.

Objective: To evaluate sperm cryopreservation-induced injuries using sperm plasma membrane protein P34H and alpha-tubulin as two different subcellular compartment markers.

Design: Prospective experimental study.

Setting: Academic hospital research center and fertility clinic.

Levels of P34H, a sperm protein of epididymal origin, as a predictor of conventional in vitro fertilization outcome.

A prospective double-blind study was performed to determine if Western blot detection of P34H, a sperm protein of epididymal origin that is involved in the binding to the zona pellucida, is predictive of standard IVF outcome. Our results demonstrate that the proportion of positive P34H cases that produced embryos in vitro clearly differs from cases with undetectable levels of P34H (P<.001).

Contraceptive responses of female hamsters immunized with recombinant sperm protein P26h.

Background: A number of antigens have been characterized and proposed as potential candidates for immunocontraception. P26h, a 26-kDa hamster sperm protein located on the acrosomal cap, is known to be involved in sperm-zona pellucida interactions. Furthermore, in vivo fertilization can be blocked by active immunization of male hamsters against P26h or maltose-binding protein recombinant P26h (MBP-P26h).

Macrophage migration inhibitory factor in the human epididymis and semen.

During epididymal transit, mammalian spermatozoa acquire new proteins involved in the acquisition of motility and of male gamete fertilising ability. We have previously shown that membranous vesicles called epididymosomes are involved in the transfer of epididymal-originating proteins to spermatozoa. The cytokine macrophage migration inhibitory factor (MIF) is one of these proteins but the role played by MIF in relation to epididymal sperm maturation still remains unclear.

P26h and dicarbonyl/L-xylulose reductase are two distinct proteins present in the hamster epididymis.

We have previously identified a 34 kDa protein (P34H) on the human sperm surface covering the acrosome. Using the hamster, we have also described a sperm protein, P26h, which is acquired by spermatozoa during epididymal transit. Both P34H and P26h belong to the carbonyl reductase family.

Vasectomy-dependent dysregulation of a local renin-angiotensin system in the epididymis of the cynomolgus monkey (Macaca fascicularis).

The mammalian epididymis is a fundamental organ for sperm cell maturation; it allows mammals to acquire their fertilizing ability. We have previously shown that during obstruction in cases of vasectomy, gene expression profiles were modified in human and cynomolgus monkey epididymides. Paracrine factors thus appear to be key elements in local gene expression along the epididymis.

Expression and localization of c-ros oncogene along the human excurrent duct.

Compared to other animals, the anatomy of the human epididymis appears unusual. The caput epididymis is composed mostly of efferent ducts with an undefined initial segment. The present study investigates the regionalization of c-ros in human epididymis by real-time quantitative RT-PCR, in situ hybridization and immunohistochemistry studies.

Expression of heat shock protein 70 in normal and cryptorchid human excurrent duct.

The Hsp70 heat-shock proteins are molecular chaperones that assist other proteins in their folding, transport and assembly into complexes. Most of these proteins are either constitutively expressed or induced by heat shock and other stresses. Heat shock proteins are required for spermatogenesis, and also protect cells from environmental hazards such as heat, radiation, and chemicals.