Low Sperm Production Research Articles

Does the order of copulation matter? Experimental paternity analyses in the earthworm Hormogaster elisae (Annelida: Hormogastridae)

Multiple mating and sperm storage organs allow postcopulatory sexual selection to occur. This is the first time that a paternity test has been performed in an earthworm species. Microsatellite markers are used in Hormogaster elisae to trace paternity for multiple sires. Multiple paternity was detected in some cases, showing sperm mixture even within one cocoon, suggesting the eventual mixture of the allosperm within the spermathecae. Order of copulation influences paternity, the first (P1) and third partner (P3) being the most successful. Interestingly the second partner (P2) almost lacks paternity. The most plausible hypothesis suggests the existence of sperm displacement by flushing out older sperm once the spermathecae are full, which seems to occur when they contain sperm from two partners and P3 donates. At that moment sperm is still stratified thus removing sperm from P2. Afterwards sperm from P1 and P3 would be mixed provoking an equivalent paternity. Given the endogeic nature of the earthworm, copulation was not observed, making the lack of copulation with P2 (due to the need of a recovery time) or copulation without sperm transfer (due to low sperm production rate) possible alternative hypotheses. The weight of the earthworms is related to the number of cocoons they produce but not to their viability, which in all the cases was low, probably due to laboratory conditions. The sperm was kept viable inside the spermathecae for a maximum of two years and three months, suggesting a very effective nourishment system in the epithelium of the storage structures.

A significant effect of the TSPY1 copy number on spermatogenesis efficiency and the phenotypic expression of the gr/gr deletion

AZFc deletions cause a significant phenotypic heterogeneity with respect to spermatogenesis; however, the reason for this is poorly understood. Recently, testis-specific protein Y-encoded 1 (TSPY1) copy number variation (CNV) was determined to be a potential genetic modifier of spermatogenesis. We performed a large-scale cohort study to investigate the effect of TSPY1 CNV on spermatogenesis and to elucidate the possible contribution of TSPY1 genetic variation to the phenotypic expression of AZFc deletions. Haplogrouping of the Y-chromosome and quantification of the TSPY1 copy number were performed in 2272 Han Chinese males with different spermatogenic statuses (704 males with the b2/b4 or gr/gr deletion and 1568 non-AZFc-deleted males). Our data revealed that the TSPY1 copy number distributions were significantly different among non-AZFc-deleted males with different spermatogenic phenotypes. Lower sperm production and an elevated risk of spermatogenic failure were observed in males with fewer than 21 TSPY1 copies and in those with more than 55 copies relative to men with 21-35 copies. Similar results were observed in males with the gr/gr deletion. These findings indicate that TSPY1 CNV affects an individual's susceptibility to spermatogenic failure by modulating the efficiency of spermatogenesis and strongly suggest that there is a significant quantity effect of the TSPY1 copy number on the phenotypic expression of the gr/gr deletion. To our knowledge, this CNV is the first independent genetic factor that has been clearly observed to influence the spermatogenic status of gr/gr deletion carriers. A combined genetic analysis of the TSPY1 copy number and the gr/gr deletion could inform the clinical counselling of infertile couples.

Daily sperm production: Application in studies of prenatal exposure to nanoparticles in mice

We investigated the influence of maternal airway exposure to nanoparticulate titanium dioxide (TiO2, UV-Titan) and carbon black (CB, Printex90), on male reproductive function in the two following generations. Time-mated C57BL/6J mice were exposed by inhalation to UV-Titan, or by intratracheal instillation with Printex90. Body and testicle weight, sperm content per g testicular parenchyma and daily sperm production (DSP) were assessed. The protocol for assessment of DSP was optimized for application in mice (C57BL/6J) and the influence of different parameters was studied. Maternal particulate exposure did not affect DSP statistically significantly in the F1 generation, although TiO2 tended to reduce sperm counts. Overall, time-to-first F2 litter increased with decreasing sperm production. There was no effect on sperm production in the F2 generation originating after TiO2 exposure. F2 offspring, whose fathers were prenatally exposed to Printex90, showed lowered sperm production. Furthermore, we report statistically significant differences in sperm production between mouse strains.

Testicular Somatic Cells, not Gonocytes, Are the Major Source of Functional Activin A during Testis Morphogenesis

Proper development of the seminiferous tubules (or testis cords in embryos) is critical for male fertility. Sertoli cells, somatic components of the seminiferous tubules, serve as nurse cells to the male germline, and thus their numbers decide the quantity of sperm output in adulthood. We previously identified activin A, the protein product of the activin βA (Inhba) gene, as a key regulator of murine Sertoli cell proliferation and testis cord expansion during embryogenesis. Although our genetic studies implicated fetal Leydig cells as the primary producers of testicular activin A, gonocytes are another potential source. To investigate the relative contribution of gonocyte-derived activin A to testis morphogenesis, we compared testis development in the Inhba global knockout mouse, which lacks activin A production in all cells (including the gonocytes), and a steroidogenic factor 1 (Sf1)-specific conditional knockout model in which activin A expression in testicular somatic cells is disrupted but gonocyte expression of activin A remains intact. Surprisingly, testis development was comparable in these two models of activin A insufficiency, with similar reductions in Sertoli cell proliferation and minor differences in testis histology. Thus, our findings suggest activin A from male gonocytes is insufficient to promote Sertoli cell proliferation and testis cord expansion in the absence of somatic cell-derived activin A. Evaluation of adult male mice with fetal disruption of activin A revealed reduced testis size, lowered sperm production, altered testicular histology, and elevated plasma FSH levels, defects reminiscent of human cases of androgen-sufficient idiopathic oligozoospermia.

The effect of bacterial contamination of semen on sperm chromatin integrity and standard semen parameters in men from infertile couples

A considerable proportion of male factor infertility cases are associated with inflammatory processes. The most common sexually transmissible agents causing sexually transmitted diseases in industrial countries are Chlamydia trachomatis, genital Ureaplasma and Mycoplasma spp. This study was undertaken to investigate whether these bacterial contaminants in semen affect sperm quality parameters and particularly DNA integrity (detected by sperm chromatin structure assay) in males from infertile couples (n = 293). The results showed that semen contaminations with the investigated bacterial species were not associated with sperm DNA fragmentation. However, contaminations with Mycoplasma spp. and C. trachomatis were associated with decreased sperm concentrations. Total sperm numbers in contaminated semen samples tended to be decreased, but not significantly. Mycoplasma had the highest adverse effect on sperm quality (concentration, motility, morphology and DNA condensation). Antibiotic therapy of the selected 47 men was successful in 55%, but semen quality parameters did not improve at least up to 3 months after the therapy. The presence of pathogenic bacteria in semen is primarily associated with low sperm production. Our data showed that Mycoplasma spp. contamination of semen had the highest adverse effect on sperm quality. Sperm chromatin integrity assessed by the presence of DNA breaks was not disturbed.

The emerging role of matrix metalloproteases of the ADAM family in male germ cell apoptosis

Constitutive germ cell apoptosis during mammalian spermatogenesis is a key process for controlling sperm output and to eliminate damaged or unwanted cells. An increase or decrease in the apoptosis rate has deleterious consequences and leads to low sperm production. Apoptosis in spermatogenesis has been widely studied, but the mechanism by which it is induced under physiological or pathological conditions has not been clarified. We have recently identified the metalloprotease ADAM17 (TACE) as a putative physiological inducer of germ cell apoptosis. The mechanisms involved in regulating the shedding of the ADAM17 extracellular domain are still far from being understood, although they are important in order to understand cell-cell communications. Here, we review the available data regarding apoptosis during mammalian spermatogenesis and the localization of ADAM proteins in the male reproductive tract. We propose an integrative working model where ADAM17, p38 MAPK, protein kinase C (PKC) and the tyrosine kinase c-Abl participate in the physiological signalling cascade inducing apoptosis in germ cells. In our model, we also propose a role for the Sertoli cell in regulating the Fas/FasL system in order to induce the extrinsic pathway of apoptosis in germ cells. This working model could be applied to further understand constitutive apoptosis in spermatogenesis and in pathological conditions (e.g., varicocele) or following environmental toxicants exposure (e.g., genotoxicity or xenoestrogens).

Transcriptional and proteomic profiling of flatfish (Solea senegalensis) spermatogenesis

The Senegalese sole (Solea senegalensis) is a marine flatfish of high economic value and a target species for aquaculture. The efforts to reproduce this species in captivity have been hampered by the fact that farmed males (F1) often show lower sperm production and fertilization capacity than wild-type males (F0). Our knowledge on spermatogenesis is however limited to a few studies. In a previous work, we identified by 2-D DIGE several potential protein markers in testis for the poor reproductive performance of F1 males. Therefore, the objectives of the present study were, first, to investigate changes in genes and proteins expressed in the testis throughout spermatogenesis in F0 males by using a combination of transcriptomic and proteomic approaches and, second, to further compare the testis proteome between late spermatogenic stages of F0 and F1 fish to identify potential indicators of hampered reproductive performance in F1 fish. We identified approximately 400 genes and 49 proteins that are differentially expressed during the progression of spermatogenesis and that participate in processes such as transcriptional activation, the ubiquitin-proteasome system, sperm maturation and motility or cytoskeletal remodeling. Interestingly, a number of these proteins differed in abundance between F0 and F1 fish, pointing toward alterations in cytoskeleton, sperm motility, the ubiquitin-proteasome system and the redox state during spermiogenesis as possible causes for the decreased fertility of F1 fish.

Neuroendocrine and Genetic Control of Seasonal Reproduction in Sheep and Goats

Goats and sheep generally express seasonal variations in their sexual behaviour, spermatogenic activity (from moderate decrease to very low sperm production), gamete quality (variations in fertilization rates and embryo survival), ovulation frequency (presence or absence of ovulation), and ovulation rate (number of eggs shed per ovulation period). This induces seasonal availability of derived, fresh animal products (meat, milk and cheese) because of a more or less marked seasonal distribution of births. A complex combination of an endogenous circannual rhythm driven and synchronized by light and melatonin, which controls the pulsatile activity of GnRH neurons in the preoptic-mediobasal hypothalamus, is responsible for these changes. Dramatic and long-term neuroendocrine changes, involving different neuromediator systems and neuronal plasticity, have been shown to play a role in these processes. A strong variability between breeds exists in both species regarding the dates of onset and end of the breeding season, with a gradient of seasonality from southern to northern latitudes. Within a breed, seasonal traits are heritable; thus, genetic selection could be one way to decrease seasonality in sheep and goats in the future.

Effects of Genetic Captive-Breeding Protocols on Sperm Quality and Fertility in the White-Footed Mouse1

Mice (Peromyscus leucopus noveboracensis) from a captive-breeding program were used to test the effects of three genetic breeding protocols (minimizing mean kinship [MK], random breeding, and selection for docility [DOC]) and inbreeding levels on sperm traits and fertility. Earlier, in generation 8, one DOC replicate went extinct because of poor reproductive success. By generation 10, spermatozoa from DOC mice had more acrosome and midpiece abnormalities, which were shown to be strong determinants of fertility, as well as lower sperm production and resistance to osmotic stress. In addition, determinants of fertility, including male and female components, were assessed in a comprehensive manner. Results showed that the probability (P) of siring litters is determined by sperm number, sperm viability, and midpiece and acrosome abnormalities; that the P of siring one versus two litters is determined by tail abnormalities; and that the total number of offspring is influenced by female size and proportion of normal sperm, showing the relative importance of different sperm traits on fertility. On average, males with 20% normal sperm sired one pup per litter, and males with 70% normal sperm sired eight pups per litter. Interestingly, the proportion of normal sperm was affected by docility but not by relatively low inbreeding. However, inbreeding depression in sperm motility was detected. In the MK group, inbreeding depression not only affected sperm motility but also fertility: An increase in the coefficient of inbreeding (f) of 0.03 reduced sperm motility by 30% and translated into an offspring reduction of three pups in second litters. A genetic load of 48 fecundity equivalents was calculated.

Activin A, a product of fetal Leydig cells, is a unique paracrine regulator of Sertoli cell proliferation and fetal testis cord expansion

Formation of tubular structures relies upon complex interactions between adjacent epithelium and mesenchyme. In the embryonic testes, dramatic compartmentalization leads to the formation of testis cords (epithelium) and the surrounding interstitium (mesenchyme). Sertoli cells, the epithelial cell type within testis cords, produce signaling molecules to orchestrate testis cord formation. The interstitial fetal Leydig cells, however, are thought only to masculinize the embryo and are not known to be involved in testis cord morphogenesis. Contrary to this notion, we have identified activin A, a member of the TGF-beta protein superfamily, as a product of the murine fetal Leydig cells that acts directly upon Sertoli cells to promote their proliferation during late embryogenesis. Genetic disruption of activin betaA, the gene encoding activin A, specifically in fetal Leydig cells resulted in a failure of fetal testis cord elongation and expansion due to decreased Sertoli cell proliferation. Conditional inactivation of Smad4, the central component of TGF-beta signaling, in Sertoli cells led to testis cord dysgenesis and proliferative defects similar to those of Leydig cell-specific activin betaA knockout testes. These results indicate that activin A is the major TGF-beta protein that acts directly on Sertoli cells. Testicular dysgenesis in activin betaA and Smad4 conditional knockout embryos persists into adulthood, leading to low sperm production and abnormal testicular histology. Our findings challenge the paradigm that fetal testis development is solely under the control of Sertoli cells, by uncovering an active and essential role of fetal Leydig cells during testis cord morphogenesis.

Considerations in Evaluating Human Spermatogenesis on the Basis of Total Sperm per Ejaculate

Total number of sperm per ejaculate (TSperm) is an important measure for clinicians to provide advice to patient couples. However, TSperm per hour of abstinence (TSperm/h) is a better measure for epidemiologist-andrologist teams or clinicians to evaluate spermatogenesis because it is a rate function. This review looks at the interplay and impacts of rate of sperm accumulation in the excurrent duct system, abstinence interval, sexual arousal, and masturbation vs intercourse on observed TSperm. It also examines why and when TSperm/h might provide a meaningful quantitative evaluation of spermatogenesis (ie, rate of sperm production). There is no doubt that TSperm increases with longer abstinence, and in different men plateaus after 2-9 days. Clinicians wishing to maximize number of fully functional sperm available during intercourse, or for artificial insemination, might wish to recommend 6-7 days of abstinence. Diagnostically, the important feature is TSperm/h. After abstinence interval exceeds 64-72 hours, TSperm/h has started to decline in most nonoligozoospermic men as rate of sperm accumulation in the excurrent ducts approaches zero; apparently increasingly more sperm are voided in urine. Clinicians or epidemiologist-andrologist teams wishing to have optimal distinction among individuals with high, typical, or low sperm production (ie, normal or abnormal spermatogenesis) should accurately measure TSperm/h for samples provided after 42-54 hours' abstinence (never <or=36 or >64 hours). Longer abstinence intervals reward men with poor sperm production, because sperm accumulate in the excurrent ducts for 7 days or more of abstinence, and penalize men with good sperm production, because after 3 days or less of abstinence their excurrent ducts probably are full.

Total Sperm per Ejaculate of Men: Obtaining a Meaningful Value or a Mean Value With Appropriate Precision

We retrospectively mined and modeled data to answer 3 questions. 1) Relative to an estimate based on approximately 20 semen samples, how imprecise is an estimate of an individual's total sperm per ejaculate (TSperm) based on 1 sample? 2) What is the impact of abstinence interval on TSperm and TSperm/h? 3) How many samples are needed to provide a meaningful estimate of an individual's mean TSperm or TSperm/h? Data were for 18-20 consecutive masturbation samples from each of 48 semen donors. Modeling exploited the gamma distribution of values for TSperm and a unique approach to project to future samples. Answers: 1) Within-individual coefficients of variation were similar for TSperm or TSperm/h abstinence and ranged from 17% to 51%; average approximately 34%. TSperm or TSperm/h in any individual sample from a given donor was between -20% and +20% of the mean value in 48% of 18-20 samples per individual. 2) For a majority of individuals, TSperm increased in a nearly linear manner through approximately 72 hours of abstinence. TSperm and TSperm/h after 18-36 hours' abstinence are high. To obtain meaningful values for diagnostic purposes and maximize distinction of individuals with relatively low or high sperm production, the requested abstinence should be 42-54 hours with an upper limit of 64 hours. For individuals producing few sperm, 7 days or more of abstinence might be appropriate to obtain sperm for insemination. 3) At least 3 samples from a hypothetical future subject are recommended for most applications. Assuming 60 hours' abstinence, 80% confidence limits for TSperm/h for 1, 3, or 6 samples would be 70%-163%, 80%-130%, or 85%-120% of the mean for observed values. In only approximately 50% of cases would TSperm/h for a single sample be within -16% and +30% of the true mean value for that subject. Pooling values for TSperm in samples obtained after 18-36 or 72-168 hours' abstinence with values for TSperm obtained after 42-64 hours is inappropriate. Reliance on TSperm for a single sample per subject is unwise.

Sexual Development and Fertility of Loxl1−/– Male Mice

Our objective was to investigate the genitourinary defects and fertility of the male lysyl oxidase-like 1 gene (Loxl1) knockout (Loxl1(-/-)) mouse, with particular attention to fecundity and testicular, epididymal, gubernacular, and penile histopathology, which may lead us to a better understanding of the role of the elastin-homeostasis gene, LOXL1, in male sexual development. Genital morphometric evaluation of 6- to 9-month-old male Loxl1(-/-) mice (n = 26) was compared with C57Bl/6 controls (n = 24). Measurements included: body weight, scrotal development, evidence of feminization (nipples or vaginal pouch), penile malformations, anogenital distance, and absence/presence and size of perineal bulge. Sperm production was estimated using a standardized technique. A breeding program was conducted to determine how much of the infertility observed in Loxl1(-/-) pairs was due to the male factor. Finally, we performed histopathologic comparison of the genitourinary organs of Loxl1(-/-) and control mice. Loxl1(-/-) mice weighed less than their age-matched C57Bl/6 counterparts (P < .001). Size-adjusted perineal bulge was larger (P < .001), and resting location of the gonads was higher intra-abdominally (P = .048) in the Loxl1(-/-) mice. Estimates of daily sperm counts revealed that the Loxl1(-/-) mice had lower sperm production (P = .048). Loxl1(-/-) males bred with control females demonstrated relative fecundity values intermediate between Loxl1(-/-) pairs (lowest fecundity) and control pairs (highest fecundity), suggesting a component of male-factor infertility. No histologic differences were noted using hematoxylin-eosin or specialized elastin staining of the gonads, gubernaculum, and penis. Although further studies are warranted, these findings suggest a subtle and likely multifactorial role of the LOXL1 protein in male sexual development and fertility.

Alkaline phosphatase activity of epididymal contents in boars with normal or reduced spermatogenesis.

The alkaline phosphatase activity was measured in testicular fluid and in epididymal plasma from caput and cauda epididymidis in boars with normal sperm production and in boars in which the number of spermatozoa passing from the testis to the epididymidis was reduced. The testicular fluid and the epididymal plasma from caput epididymidis contained low amounts of alkaline phosphatase in comparison with epididymal plasma from the cauda. This applies to both groups of boars e.g. boars with normal as well as with totally lacking or lowered sperm production. As no fluid resorption takes place between caput and cauda the distal part of the epididymidis must be the main production site for alkaline phosphatase. The production there is not related to the presence of spermatozoa in the duct. In the caput, on the other hand, it seems that the level of alkaline phosphatase in some way is influenced by the sperm supply to the duct.

Melatonin and aromatase stimulating activity of human seminal plasma

Melatonin concentrations and aromatase stimulating activity were determined in human seminal plasma and correlated with sperm density and motility. Aromatase stimulating activity was determined with an in vitro rat granulosa cell system and melatonin by radioimmunoassay. Compared to normal semen, aromatase stimulating activity was lower in azoospermic individuals, while melatonin was higher in oligospermic and azoospermic samples. Aromatase stimulating activity correlated positively with sperm concentrations and a negative correlation was found between melatonin and sperm progression. These findings suggest that low sperm production is associated with low aromatase stimulating bioactivity in seminal plasma; and melatonin may have an effect upon both sperm production and motility.

2‐D DIGE analysis of Senegalese sole (Solea senegalensis) testis proteome in wild‐caught and hormone‐treated F1 fish

In the farmed flatfish Senegalese sole, F1 males reared in captivity often show lower sperm production and fertilization capacity than wild-caught males. To gain insights into the molecular mechanisms that may be altered in the F1 testis, we used 2-D DIGE to compare the protein profiling of the testis of wild-caught males at the spermiation stage with that of F1 males showing different stages of germ cell development after hormone treatment in vivo. The abundance of 58 out of 1014 protein spots was found to differ significantly between the groups. De novo identification of these proteins by MS/MS revealed that proteins implicated in oxidoreductase activity, protein catabolism, formation of the zona pellucida receptor, cytoskeleton organization, and lipid binding and metabolism, were regulated in the F1 testes as germ cell development progressed. However, distinct isoforms or PTMs of some of these proteins, as well as of proteins involved in iron and glucose metabolism and ATP production, were expressed at lower levels in the testes of F1 males than in wild fish regardless of the hormone treatment. These results contribute to identifying proteins associated with spermatogenesis not previously described in teleosts, and suggest potential mechanisms that may be involved in the poor reproductive performance of Senegalese sole F1 males.

Female-driven mechanisms, ejaculate size and quality contribute to the lower fertility of sex-ratio distorter males in Drosophila simulans

BackgroundSex-ratio meiotic drive refers to the preferential transmission of the X chromosome by XY males. The loss of Y-bearing sperm is caused by an X-linked distorter and results in female-biased progeny. The fertility of sex-ratio (SR) males expressing the distorter is usually strongly reduced compared to wild-type males, especially when they are in competition. The aim of this study was to identify the post-copulatory mechanisms that lower the fertility of SR males in Drosophila simulans. Parameters contributing to male fertility were measured in single and double mating conditions.ResultsThe most detrimental effect on SR males fertility is due to the size of their ejaculate which is half that of wild-type males. Sperm viability and sperm use by the females are also reduced. Sex-ratio males are poor sperm competitors in both offence and defence. We found evidence for sperm release from the female reproductive tract that specifically affects SR males. It results in the removal of stored sperm from a first SR mate without the action of the sperm of the second male. In addition, females mated once with an SR male remate more frequently with wild-type males.ConclusionThe paternity reduction of SR males in competitive conditions is greater than that attributable to their low sperm production and could prevent the spread of distorter X chromosomes in populations when multiple mating occur. The female-driven mechanisms are shown to play a major role both throughout the post-copulatory selective process and increased polyandry. The variation in male reproductive performance may drive the evolution of sexual learning capability of females.

Histone H4 acetylation and AZFc involvement in germ cells of specimens of impaired spermatogenesis

To measure histone-H4 acetylation and involvement of the AZFc region in testicular mixed atrophy. Prospective study. University-affiliated medical center. Azoospermic men (n = 23) who underwent testicular sperm extraction and preparation for intracytoplasmic sperm injection (ICSI) divided into obstructive azoospermia with complete spermatogenesis (group A), testicular mixed atrophy (group B), and testicular mixed atrophy associated with AZFc deletion (group C). Testicular biopsy evaluation by Western blotting and quantitative immunohistochemistry of histone-H4 hyperacetylation (Hypac-H4) and lysine-12 acetylation (Lys12ac-H4). Percentage of spermatogonia and spermatids stained by Hypac-H4 and Lys12ac-H4 antibodies in retrieved specimens. The percentage of spermatogonia stained for Hypac-H4 and Lys12ac-H4 in groups B and C was statistically significantly reduced. The percentage of elongated spermatids showing positive staining to Hypac-H4 was statistically significantly lower in group B than group A. The percentage of Lys12ac-H4-labeled spermatids was similar for all groups. Hypac-H4 and Lys12ac-H4 processes were highly correlated in spermatogonia but not in spermatids. The reduced percentage of spermatogonia with Hypac-H4 and Lys12ac-H4 in groups B and C may contribute to lower sperm production in mixed atrophy. Spermatids Hypac-H4 impairment in mixed atrophy did not deteriorate further by AZFc region deletion.

Environmental toxicant-induced germ cell apoptosis in the human fetal testis

Disorders of the male reproductive system are increasing in prevalence. The term testicular dysgenesis syndrome emphasizes the importance of developmental influences on the aetiology of conditions including cryptorchidism, testicular germ cell cancer and reduced spermatogenesis. Men whose mothers smoked during pregnancy have lower sperm production. Cigarette smoke contains agents acting on the aryl hydrocarbon receptor (AHR). We have investigated the presence of AHR in the developing human testis and the effects of functional activation. Immunohistochemistry determined AHR to be expressed by germ cells in the human testis between 7 and 19 week gestation, but not by other cells. Treatment of cultured fetal testis with an AHR ligand present in tobacco smoke increased markers of cell apoptosis, and this was prevented by an AHR receptor antagonist. Immunohistochemistry indicated that apoptosis was restricted to germ cells. Germ cells in the developing human testis are a target for regulation by AHR ligands. Activation of AHR by environmental toxicants and AHR-induced apoptotic pathways may be the mechanism of action underlying the epidemiological findings of reduced spermatogenesis in men exposed to cigarette smoke before birth, and may also be of importance in other conditions comprising the testicular dysgenesis syndrome.

Glycol ethers and semen quality: a cross-sectional study among male workers in the Paris Municipality

Objectives: Apparent increases in human male reproductive disorders, including low sperm production, may have occurred because of increased chemical exposure. Various glycol ether-based solvents have pronounced adverse effects on sperm...