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B Robaire

Publications and source records attributed to B Robaire.

At least 19 recordsLinked to original sources
PubMed2006

A unique configuration of genome-wide DNA methylation patterns in the testis.

In the mammalian lifecycle, the two periods of genome-wide epigenetic reprogramming are in the early embryo, when somatic patterns are set, and during germ cell development. Although some differences between the reprogrammed states of somatic and germ cells have been reported, overall patterns of genomic methylation are considered to be similar. Using restriction landmark genomic scanning to examine approximately 2,600 loci distributed randomly throughout the genome, we find that the methylation status of testicular DNA is highly distinct, displaying eightfold the number of hypomethylated loci relative to somatic tissues. Identification and analysis of >300 loci show that these regions are generally located within nonrepetitive sequences that are away from CpG islands and 5' regions of genes. We show that a contributing factor for these differences is that the methylation state of non-CpG-island DNA is correlated with the regional level of GC content within chromosomes and that this relationship is inverted between the testis and somatic tissues. We also show that in Dnmt3L-deficient mice, which exhibit infertility associated with abnormal chromosomal structures in germ cells, this unique testicular DNA methylation pattern is not established. These special properties of testicular DNA point to a broad, distinct epigenetic state that may be involved in maintaining a unique chromosomal structure in male germ cells.

Animals↗
PubMed2004

Effects of PNU157706, a dual 5alpha-reductase inhibitor, on gene expression in the rat epididymis.

The epididymis is the site of sperm maturation and storage. 5alpha-Reductases (types 1 and 2) are key enzymes in this tissue because they convert testosterone to dihydrotestosterone (DHT), the main androgen regulating epididymal functions. Examining the consequences of inhibiting DHT formation is likely to provide important information regarding the regulation of epididymal functions, yet few inhibitor studies have focused on this tissue. To understand better DHT-mediated regulation of epididymal gene expression, we employed a dual 5alpha-reductase inhibitor and cDNA microarrays to examine the effects of 5alpha-reductase inhibition on gene expression in the initial segment, caput, corpus, and cauda epididymidis. Inhibition of epididymal 5alpha-reductase activity by PNU157706 was confirmed by in vitro enzyme assays. Rats were treated with 0, 0.1, 1.0 or 10 mg/kg per day PNU157706 for 28 days. The weights of DHT-dependent tissues, including the epididymis, were decreased following treatment. The effect of treatment on gene expression was dose-dependent and highly segment-specific. The initial segment responded uniquely in that a similar number of genes increased and decreased in expression compared with the other segments where the majority of affected genes decreased in expression. Some of the more dramatically affected genes were involved in signal transduction as well as fatty acid and lipid metabolism, regulation of ion and fluid transport, luminal acidification, oxidative defense and protein processing and degradation. These are essential processes contributing to the formation of an optimal luminal microenvironment required for proper sperm maturation. These results provide a novel insight into the DHT-dependent mechanisms that control epididymal functions.

5-alpha Reductase Inhibitors↗
PubMed2001

Acute cyclophosphamide exposure has germ cell specific effects on the expression of stress response genes during rat spermatogenesis.

Exposure of male rats to cyclophosphamide, a commonly used anticancer and immunosuppressive drug, has been shown to alter fertility and progeny outcome in a male germ cell phase-specific manner. The effect of toxicant exposure on male germ cells depends in part on the stress response mechanisms present during the different stages of spermatogenesis. To assess how acute cyclophosphamide exposure affects the expression of stress response genes, we examined the expression of 216 genes, using gene expression arrays, in isolated rat spermatogenic cell types (pachytene spermatocytes, round spermatids, and elongating spermatids). Cyclophosphamide exposure affected gene expression in all cell types but most dramatically in round spermatids. Increased transcript levels were observed for 30 genes in round spermatids compared to seven genes in pachytene spermatocytes and two in elongating spermatids. The expression of genes involved in apoptosis, DNA-damage recognition and repair, transcriptional activation, and in the heat shock protein-chaperone response was most affected by cyclophosphamide in round spermatids. Our results demonstrate that cyclophosphamide alters the expression of stress response genes during spermatogenesis in a germ cell-specific manner. The greater response of round spermatids to cyclophosphamide suggests that this cell type may be more susceptible to the damaging effects induced by this drug, possibly due to the chromatin remodeling that is taking place at this stage of spermatogenesis. This observation is consistent with the reported higher level of abnormal progeny outcome seen when the germ cells were first exposed to cyclophosphamide as round spermatids.

Animals↗
PubMed2001

Expression of stress response genes in germ cells during spermatogenesis.

During germ cell development different spermatogenic cell types show remarkable variation in their susceptibility to stressful stimuli. Various cellular mechanisms are triggered in germ cells after exposure to stress, but the expression of only a few of the genes involved in such pathways has been studied during spermatogenesis. In the present study we determined the expression profiles of 216 stress response genes in isolated rat germ cells (pachytene spermatocytes, and round and elongating spermatids) using cDNA atlas arrays. Of the 216 genes studied, 86 were detected in pachytene spermatocytes, 82 in round spermatids, and 52 in elongating spermatids. Fifty percent (48) of the total number of genes detected during spermatogenesis were detected in all three cell types while nearly 25% (25) were expressed exclusively in pachytene spermatocytes and round spermatids; some cell specific transcripts were observed also. The use of the K means clustering method allowed us to group genes by their pattern of expression during spermatogenesis; five specific expression profiles were obtained and analyzed. To determine how stress response genes are regulated throughout spermatogenesis, we examined the expression of genes involved in stress response mechanisms such as heat shock proteins-chaperones, DNA repair, and oxidative stress. Genes belonging to these families were differentially expressed during germ cell development. We suggest that the differential expression of stress response genes during spermatogenesis contributes to the selectivity of the susceptibility of germ cells to stress.

Animals↗
PubMed2001

Dynamic changes in gene expression along the rat epididymis.

In the epididymis a series of complex, sequential events transform immature, spermatozoa into mature, motile sperm with fertilizing ability. These events are not intrinsic to germ cells but rather are a direct result of exposure to, and interaction with, the environment created by the epididymal epithelium. Regional differences along the epididymis are essential in the establishment of the environment required for sperm maturation. Although parts of this process have been identified, the molecular basis for the segment-specific differences and how they contribute to the process of sperm maturation, are not yet resolved. The identification of genes expressed in a region-specific manner will provide valuable insight into the functional differences between the regions. To characterize gene expression in the different regions of the epididymis, microarrays containing 1176 rat cDNAs were used to examine gene expression in the initial segment, caput, corpus, and cauda epididymidis of the adult Brown Norway rat. Overall, the cauda epididymidis expressed the most genes and the corpus epididymidis the fewest. A small percentage of genes (3%) were expressed highly (greater than fivefold the average expression on the array) along the tissue. Segment-specific gene expression for genes expressed at high levels was observed in all epididymal segments except the corpus epididymidis. Of the genes on the array, 36% were expressed in all four epididymal segments; expression changes that were a minimum of twofold in either direction between adjacent segments are discussed. The expression of cathepsins and oxidative stress-related genes was investigated. Six of the eight cathepsins on the array (B, C, E, H, L, and K) were expressed above twofold background and showed different levels of expression along the duct with cathepsin K showing the most dramatic change (i.e., a decrease of 87% between the initial segment and the corpus epididymidis). There was also differential expression along the epididymis of many genes associated with oxidative stress defenses. Using the power of expression array technology, we have identified novel transcripts expressed in a segment-specific manner and been able to assess how the expression of several selected gene families is modulated along the epididymis.

Animals↗
PubMed2001

Gene expression in Brown Norway rat Leydig cells: effects of age and of age-related germ cell loss.

There is a marked reduction in circulating T and a commensurate decrease in Leydig cell function in males during aging. Aging is also accompanied by progressive loss of germ cells, leading to testicular atrophy. However, in aged animals, there is no difference in T production by Leydig cells from nonregressed testes and from regressed testes. We hypothesize that there are changes in Leydig cell gene expression that accompany aging, and that different changes in gene expression result from testicular regression. To test this hypothesis, the expression of stress response genes was compared in Leydig cells isolated from young rat testes, from aged testes that were not regressed, and from aged testes that were regressed, using an array approach. Similar numbers of transcripts (n = 56-63) were detected in Leydig cells isolated from all three groups of rats. Among these, 21 transcripts were increased in Leydig cells of testes from aged nonregressed animals compared with cells from young animals; 23 were increased with subsequent testicular regression. Only 3 of these transcripts were in common. Thus, age and testicular regression affected Leydig cell transcripts in dramatically different ways. Furthermore, none of the transcripts that decreased when comparing Leydig cells of young and aged nonregressed animals were the same as those that decreased when comparing aged nonregressed and aged regressed animals. In individual gene families, the steady state concentrations of transcripts in Leydig cells from aging and aging regressed testes often differed. Thus, there are major differences in the expression of a wide variety of stress response genes in Leydig cells associated with aging and testicular regression.

Aging↗
PubMed2000

Paternal exposure to cyclophosphamide induces DNA damage and alters the expression of DNA repair genes in the rat preimplantation embryo.

Chronic low dose treatment of male rats with cyclophosphamide, an anticancer alkylating agent, damages male germ cells, resulting in greater than 80% peri-implantation progeny loss. Little transcription or repair takes place in the DNA of post-meiotic male germ cells. The spermatozoal genome regains its transcriptional capacity in the fertilized oocyte. We hypothesized that as a consequence of exposure of male rats to cyclophosphamide DNA damage to the male genome is transmitted to the conceptus; furthermore, this damage leads to alterations in the expression profiles of DNA repair genes during preimplantation development. Male rats were treated with either saline or cyclophosphamide (6mg/kg/day, 4-6 weeks) and mated to control females; 1-8 cell stage embryos were collected. The alkaline comet assay was used to assess DNA damage in 1-cell embryos. A significantly higher percentage (68%) of the embryos fertilized by cyclophosphamide-exposed spermatozoa displayed a comet indicative of DNA damage, compared to those sired by control males (18%). The in situ transcription/antisense RNA approach was used to determine if DNA damage alters the expression of DNA repair genes in early embryos. Dramatic increases in the transcripts for selected members of the nucleotide excision repair family (XPC, XPE and PCNA), mismatch repair family (PMS1), and recombination repair family (RAD50) were found in 1-cell stage embryos sired by cyclophosphamide-treated males compared to controls, while decreases in the expression of base excision repair family members (UNG1, UNG2, and XRCC1) and in recombination repair transcripts (RAD54) were observed. By the 8-cell stage, transcripts for specific members of the nucleotide excision repair family (XPC) and mismatch repair family (MSH2, PMS2) were elevated greatly in control embryos compared to embryos sired by drug-treated males; in contrast, transcripts for other members of the nucleotide excision repair family (XPE, PCNA), as well as some of the base excision repair family (UNG1), were elevated in embryos sired by drug-treated males. Therefore, DNA damage incurred in spermatozoa, following cyclophosphamide exposure is associated with alterations in the expression profiles of DNA repair genes in preimplantation embryos as early as the 1-cell stage. Genotoxic stress may disturb the nuclear remodeling and reprogramming events that follow fertilization and precede zygotic genome activation.

Animals↗
PubMed2000

Paternal exposure to cyclophosphamide dysregulates the gene activation program in rat preimplantation embryos.

Although there has been progress in determining the mechanisms by which maternal toxicant exposure affects progeny, there is little information on the actions of drugs administered to the father. We investigated the effects of pre-conceptional paternal exposure to cyclophosphamide, an anti-cancer agent, on embryonic gene activation in the rat. The male pronucleus was formed earlier in embryos sired by cyclophosphamide-treated male rats than in those sired by controls; early male pronucleus formation was followed by alterations in the gene activation program. BrUTP incorporation into RNA and Sp1 transcription factor immunostaining were increased and spread over both cytoplasmic and nuclear compartments in 2-cell embryos sired by cyclophosphamide-treated males compared to controls. Total RNA synthesis was constant in 1-8 cell embryos sired by drug-treated fathers, while in control embryos RNA synthesis increased four-fold to peak at the 4-cell stage. In 2-cell embryos sired by drug-treated males, the relative abundance of candidate imprinted genes was elevated significantly above control; a peak in the expression of these genes was not observed until the 8-cell stage in control embryos. Thus, paternal drug exposure temporally and spatially dysregulated rat zygotic gene activation, altering the developmental clock.

Animals↗
PubMed2000

Paternal exposure to cyclophosphamide alters cell-cell contacts and activation of embryonic transcription in the preimplantation rat embryo.

Paternal exposure to chronic low doses of cyclophosphamide, an anticancer agent, results in aberrant embryonic development of the progeny. We hypothesized that paternal exposure to cyclophosphamide disturbs zygotic gene activity regulating proper progression through preimplantation development and that this disturbance results in improper cell-cell interactions. To test this hypothesis, we analyzed cell-cell interactions and the expression of cytoskeletal elements in preimplantation embryos sired by male rats gavaged with saline or 6 mg kg(-1) day(-1) cyclophosphamide for 5 wk. Embryos from control litters had 4-12 cells on Day 2 of gestation; cell-cell contacts were observed consistently. Embryos from litters sired by cyclophosphamide-treated males were frequently abnormal and had lower cell numbers and decreased cell-cell contacts. Steady state concentrations of the mRNAs for cell adhesion molecules (cadherins and connexin 43) and structural proteins (beta-actin, collagen, and vimentin) were low in two- and four-cell control embryos; expression increased dramatically by the eight-cell stage. In contrast, embryos sired by cyclophosphamide-treated males displayed the highest expression of most trancripts at the two-cell stage. In parallel with the mRNA profiles, E-cadherin immmunoreactivity was nearly absent in two-cell control embryos and was strong by the eight-cell stage; immunoreactivity in embryos sired by drug-treated fathers was strong at the two-cell stage but absent at later stages. Thus, drug exposure of the paternal genome led to dysregulated expression of structural elements and decreased cell interactions during preimplantation embryonic development.

Animals↗
PubMed2000

Critical windows of exposure for children's health: the reproductive system in animals and humans.

Drugs and environmental chemicals can adversely affect the reproductive system. Currently, available data indicate that the consequences of exposure depend on the nature of the chemical, its target, and the timing of exposure relative to critical windows in development of the reproductive system. The reproductive system is designed to produce gametes in far greater excess than would seem to be necessary for the survival of species. Ten to hundreds of millions of spermatozoa are generated daily by most adult male mammals, yet very few of these germ cells succeed in transmitting their genetic material to the next generation. Although the number of oocytes produced in mammalian females is more limited, and their production occurs only during fetal life, most ovaries contain several orders of magnitude more oocytes than ever will be fertilized. Toxicant exposures may affect critical events in the development of the reproductive system, ranging from early primordial germ cell determination to gonadal differentiation, gametogenesis, external genitalia, or signaling events regulating sexual behavior. Although there are differences between the human reproductive system and that of the usual animal models, such models have been extremely useful in assessing risks for key human reproductive and developmental processes. The objectives for future studies should include the elucidation of the specific cellular and molecular targets of known toxicants; the design of a systematic approach to the identification of reproductive toxicants; and the development of sensitive, specific, and predictive animal models, minimally invasive surrogate markers, or in vitro tests to assess reproductive system function during embryonic, postnatal, and adult life.

Adult↗
PubMed1999

Segment-specific changes with age in the expression of junctional proteins and the permeability of the blood-epididymis barrier in rats.

In aging Brown Norway rats, there is a striking increase in the number of halo cells in the epididymis; this reflects an activation of the immune system. As the blood-epididymis barrier should protect from immunological attack, we hypothesized that there would be changes in the structure and function of this barrier with age. To test this hypothesis, we assessed the immunocytochemical localization of occludin, ZO-1, and E-cadherin, as well as the lanthanum nitrate permeability of the blood-epididymis barrier, in the epididymides of Brown Norway rats aged 3, 18, and 24 mo. In the initial segment, occludin, ZO-1, and E-cadherin immunostaining was observed at the apico-lateral junction between principal cells in the 3-mo-old animals; with increasing age, occludin and ZO-1 reactivity decreased, while E-cadherin staining increased along the lateral membrane between principal cells. In the caput, corpus, and cauda epididymidis, occludin, ZO-1, and E-cadherin immunostaining showed segment-specific and age-dependent differences in their staining patterns. The most dramatic changes were seen in the corpus epididymidis with age; the intense E-cadherin cytoplasmic staining that was observed at 3 mo was absent by 24 mo, and no occludin or ZO-1 reactivity was observed in older animals. The greatest penetration of lanthanum nitrate across the blood-epididymis barrier and in the lumen was seen in the aging corpus epididymidis, while there was no barrier permeability in the initial segment or cauda epididymidis of the aged animals. Taken together, these data indicate that there are segment-specific decreases in the structural and functional integrity of the blood-epididymis barrier with age, most notably in the corpus epididymidis.

Aging↗
PubMed1999

Distribution of immune cells in the epididymis of the aging Brown Norway rat is segment-specific and related to the luminal content.

Remarkable changes occur during aging in the testis and epididymis of the Brown Norway rat. A dramatic increase in the number of halo cells, which are present in the epididymal epithelium and originate from the immune system, is found in animals of increasing age. Halo cells have been postulated to be either lymphocytes or monocytes. We hypothesized that halo cells are a mixture of different immune cells and that their relative composition changes with age. To verify this hypothesis, markers for helper T lymphocytes, cytotoxic T lymphocytes, B lymphocytes, and monocytes-macrophages were used to identify the major categories of immune cells in the epididymides of Brown Norway rats ranging in age from 3 to 24 mo. The numbers of immunocompetent cells in the epididymis were determined in relation to age, epididymal segment, and luminal content. We found that monocytes, helper T lymphocytes, and cytotoxic T lymphocytes belong to the population of halo cells. In addition, a segment-specific increase with age in the number of these immune cells was noted. Finally, we report a segment-specific recruitment of cytotoxic T lymphocytes and monocytes-macrophages in the epididymal epithelium of aged rats whose epididymal lumen contained few spermatozoa. We postulate that accumulation of damaged epithelial cells and antigens of germ cell origin, leaking through a dysfunctional blood-epididymis barrier, may contribute to the active recruitment of immune cells with age.

Aging↗
PubMed1998

Paternal age affects fertility and progeny outcome in the Brown Norway rat.

OBJECTIVE: To investigate the effects of paternal age on fertility and progeny outcome using the Brown Norway rat model. DESIGN: Controlled prospective study. SETTING: McIntyre Animal Centre, McGill University, Montreal, Quebec, Canada. INTERVENTION(S): Brown Norway male rats of increasing age were mated to young Sprague-Dawley females. MAIN OUTCOME MEASURE(S): Pregnancy outcome was assessed by counting the numbers of corpora lutea, resorptions, and live fetuses on day 20 of gestation. To evaluate progeny outcome, pups were examined for external malformations and weighed daily for 2 months. RESULT(S): There were no significant changes in the numbers of resorptions, offspring, or in the incidence of external malformations. However, there was an increase in preimplantation loss (corpora lutea minus implantation sites) in litters fathered by older males. Furthermore, a significant decrease in the average fetal weight was found with increasing paternal age. A significant increase in neonatal deaths for progeny fathered by older males also was found. CONCLUSION(S): These results indicate that the quality of spermatozoa decreases as males age.

Animals↗
PubMed1998

A cell cycle regulating receptor is localized on cell surface and in nuclei of mitotically and meiotically dividing cells.

We previously showed that a heterodimeric surface receptor of molecular weight 65,000 (p65) and 95,000 (p95) is expressed on the surface of proliferating cells such as activated T lymphocytes and neural precursors. This p65/p95 receptor is recognized by a monoclonal antibody and by type 3 reovirus hemagglutinin. Binding of the surface p65/p95 receptor leads to a growth arrest of mitotic cells and a consequent inhibition of proliferation. The p65/p95 receptor was demonstrated to be associated with kinase activity. Because p65/p95 is involved in the regulation of mitotic cell division, we sought to study the cellular distribution of the receptor and its possible role in meiotic cell division. Immunohistochemical labeling and flow cytometry studies were done using adult rat testes and cell lines. All cells undergoing mitotic or meiotic division in the rat testis expressed the p65/p95 receptor; cells that do not divide did not express receptors. Dividing cells had two receptor pools. As previously reported for several mitotically active tissues, a pool of receptors was localized on the cell surface. Interestingly, a pool of receptors was also seen intracellularly over the nucleus of labeled cells. The nuclear label seemed to be associated with chromosomes during specific stages of the mitotic and the two meiotic divisions, suggesting a role in the regulation of nuclear events. Further studies on this receptor and the function of the nuclear pool should provide a better understanding of the control of cell division.

Age Factors↗
PubMed1998

Segment-specific morphological changes in aging Brown Norway rat epididymis.

In aging Brown Norway rats, both spermatogenesis and steroidogenesis decrease. Little is known about changes in the epididymis during aging. However, since the two major components entering the epididymis from the testis change, we hypothesized that epididymal histology would be affected by advancing age. The epididymides of Brown Norway rats ranging in age from 3 to 24 mo were prepared for light and electron microscopy. Striking quantitative and qualitative changes were noted. There was an age-dependent increase in the thickness of the basal membrane and in the number of halo cells. There were also major segment-specific changes in the appearance of cells along the epididymis with age. At 12 mo, basal cells in the initial segment emitted pseudopods into the basement membrane. By 18 mo, in the caput epididymidis, clear cells were filled with lysosomes; these cells frequently showed bulging protrusions into the lumen. In the corpus epididymidis, the cytoplasm of principal cells had numerous large lysosomes both below and above the nucleus; apical cells were usually occupied by one giant membranous lysosome. In the proximal cauda, clear cells became filled with dense lysosomes, and principal cells presented large clear vacuoles; debris from spermatozoa was found in the larger vacuoles. In summary, aging of the epididymis was accompanied by the emergence of characteristic features of aging and activation of the immune system. Furthermore, there were many cell- and segment-specific changes. Finally, these changes were not related to the presence of spermatozoa, often preceding their disappearance, thus indicating that there may be an intrinsic mechanism of aging in epididymal epithelial cells.

Aging↗
PubMed1998

Orchidectomy induces a wave of apoptotic cell death in the epididymis.

The epididymis is the site where spermatozoa are matured and stored. After orchidectomy, this tissue loses up to 80% of its weight. In the prostate, androgen withdrawal by orchidectomy is associated with apoptotic cell death. The objective of the present study was to investigate whether apoptotic cell death is involved in the androgen-dependent weight loss found in the rat epididymis after orchidectomy. Adult male Sprague-Dawley rats were orchidectomized, and apoptotic cells were identified by in situ TUNEL (TdT-mediated dUTP-digoxigenin nick end-labeling) apoptosis detection. Apoptosis first appeared in the epithelium of the initial segment of the epididymis 18 h after orchidectomy, reached a maximum on day 2, and disappeared by day 5 postorchidectomy. In the caput epididymidis, apoptosis was first found after 24 h, reached a maximum by day 3, and was detectable until day 5. In the corpus epididymidis, apoptosis was first seen on day 4, peaked on day 5, and was undetectable by day 6 postorchidectomy. In the cauda epididymidis, apoptosis was first seen on day 5, peaked on day 6, and was occasionally detected on day 7. Throughout the rat epididymis, apoptotic cell death was localized specifically to principal cells. The presence of apoptosis was confirmed with the observation of a ladder of nucleosomal sized DNA fragmentation by using agarose gel electrophoresis. Androgen replacement therapy after orchidectomy demonstrated that apoptosis in the caput, corpus, and cauda epididymidis was androgen dependent. However, androgens alone could not completely prevent apoptosis in the initial segment of the epididymis. Efferent duct ligation induced a similar pattern of apoptosis in the initial segment of the epididymis as that seen after orchidectomy, but there were fewer apoptotic cells in the caput epididymidis, and no apoptotic cell death in the corpus and cauda epididymidis. We conclude that withdrawal of androgen by orchidectomy induces a wave of apoptotic cell death in the epididymis; we hypothesize that apoptosis in the initial segment is caused primarily by withdrawal of androgen as well as by luminal components coming from the testis.

Animals↗
PubMed1998

Regulation of apoptotic cell death in the rat epididymis.

The rat epididymis decreases markedly in weight after orchidectomy. In these studies, we demonstrate that a time-dependent wave of apoptotic cell death occurs in some principal cells after orchidectomy. This wave moves coincidentally with the luminal content of the epididymis. Androgen treatment at the time of orchidectomy can prevent apoptotic death in all regions of the epididymis except the initial segment (Robaire and Hermo, 1988, similar to zone 1a defined by Reid and Cleland, 1957). After unilateral efferent duct ligation, apoptotic cell death in the initial segment of the epididymis is similar to that seen after orchidectomy, reduced in the caput (zones 1b,c, 2 and 3 as defined by Reid and Cleland, 1957) and absent from the corpus (defined as zones 4, by Reid and Cleland, 1957) and cauda epididymidis (defined as zones 5 and 6 by Reid and Cleland, 1957). Together, these results indicate that principal cells differ in their responses to androgens and other testicular factors both in any given cross-section and with respect to their position along the epididymis.

Androgens↗