Arrest Of Spermatogenesis Research Articles

Overexpression of mouse follistatin causes reproductive defects in transgenic mice.

Follistatin is an activin-binding protein that can act as an activin antagonist in vitro. Follistatin also binds heparin sulfate proteoglycans and may function as a reservoir for activins in vivo. In the mouse, follistatin mRNA is first detected in the deciduum on embryonic day 5.5 and later in the developing hindbrain, somites, vibrissae, teeth, epidermis, and muscle. We have previously shown that follistatin-deficient mice have numerous embryonic defects including shiny, taut skin, growth retardation, and cleft palate leading to death within hours of birth. To further define the roles of follistatin during mammalian reproduction and development, we created gain-of-function mutant mice in which mouse follistatin is overexpressed. The mouse metallothionein (MT)-I promoter was placed upstream of the six-exon mouse follistatin (FS) gene. To distinguish wild-type and transgenic follistatin mRNA, the 3'-untranslated region of the mouse follistatin gene was replaced with the SV40 untranslated and polyA sequences. Three male and two female founder transgenic mice were produced, were fertile, and transmitted the transgene to offspring. Northern blot analysis demonstrated that the transgene mRNA was expressed at varying levels in the livers of offspring from four of five of the transgenic lines and was expressed in the testes in all five lines. In MT-FS line 4, which had the highest expression of the transgene mRNA in the liver, the transgene transcripts were also present in multiple other tissues. Phenotypically, the MT-FS transgenic lines had defects in the testis, ovary, and hair. Mice from MT-FS lines 7 and 10 had slightly decreased testis size, whereas mice from lines 4, 5, and 9 had much smaller testes and shiny, somewhat irregular, fur. Histological analysis of the adult testes from line 5 and 9 males showed variable degrees of Leydig cell hyperplasia, an arrest of spermatogenesis, and seminiferous tubular degeneration leading to infertility. Female transgenic mice from lines 4 and 9 had thin uteri and small ovaries due to a block in folliculogenesis at various stages. Many of the line 9 female mice eventually became infertile, and all of the line 4 female mice were infertile. Suppressed serum FSH levels were seen in only the line 4 transgenic male and female mice, the line with widespread expression of the transgene. Serum FSH levels were not significantly different in gonadectomized wild-type and line 5 transgenic male mice despite high levels of the follistatin transgene mRNA in the liver of these transgenic mice. These results suggest that follistatin exerts its effects at the levels of the gonads and pituitary as a local regulator of activin and possibly other transforming growth factor-beta family members.

Distribution of heat-shock protein 60 immunoreactivity in testes of infertile men.

The immunohistochemical localization of heat-shock protein 60 (hsp60) was investigated in testicular biopsies obtained from 121 adult men with disturbed fertility. In normal unaffected tubules, hsp60 immunoreactivity was localized to spermatogonia, primary spermatocytes and Sertoli cells. In spermatogonia, cytosolic and mitochondrial labelling could be differentiated. In general, the number of stained spermatogonia decreased with the loss of spermatogenic function. A significant (P<0.01) reduction of stained spermatogonia was observed in testes with maturation arrest of spermatogenesis at the level of primary spermatocytes (30.2+/-21.6%) compared with testes exhibiting normal spermatogenesis. In addition, the decrease in the score correlated significantly with the diminution of cytosolic hsp60 immmunolabelling (coefficient r=0.25, P=0.03). There was a significant difference (P<0.01) in the percentage of cytosolic-stained spermatogonia in testes with a score equal to or greater than 5 (14.7+/-9.8%) and a score less than 5 (8. 9+/-6.9%). These observations suggest that a low level of hsp60 expression in spermatogonia may lead to a different pattern of protection, which in turn could be involved in low spermatogenic efficiency.

Arrest of spermatogenesis and defective breast development in mice lacking A-myb.

The Myb gene family currently consists of three members, named A-, B- and c-myb. These genes encode nuclear proteins that bind DNA in a sequence-specific manner and function as regulators of transcription. In adult male mice, A-myb is expressed predominantly in male germ cells. In female mice, A-myb is expressed in breast ductal epithelium, mainly during pregnancy-induced ductal branching and alveolar development. We report here that mice homozygous for a germline mutation in A-myb develop to term but show defects in growth after birth and male infertility due to a block in spermatogenesis. Morphological examination of the testes of A-myb-/- males revealed that the germ cells enter meiotic prophase and arrest at pachytene. In adult homozygous null A-myb female mice, the breast epithelial compartment showed underdevelopment of breast tissue following pregnancy and the female mice were unable to nurse their newborn pups. These results demonstrate that A-myb plays a critical role in spermatogenesis and mammary gland development.

Successful fertilization and pregnancy after injection of frozen-thawed round spermatids into human oocytes.

The effect of cryopreservation on the integrity and fertilizing capacity of round spermatids was studied in two azoospermic patients. In December 1995 the patients, both with maturation arrest of spermatogenesis, were submitted to testicular sperm extraction (TESE) after an extensive examination of their ejaculate. Only round spermatids were found after testicular biopsy. Some of the spermatids were isolated and used for a first injection, while the remainder of the preparation was cryopreserved for successive cycles. Because of the failure of the first attempt, 3 months later, the same two patients were submitted to a second one. The frozen preparation was thawed and examined to evaluate the integrity and the viability of surviving round spermatids. More than 70% of the thawed spermatids were viable for injection. Fifteen oocytes at metaphase II, retrieved from the patients' wives, were microinjected with thawed round spermatids. Eighteen hours after the injection, seven out of 15 oocytes showed normal fertilization, with the presence of two pronuclei. The zygotes were cultured to observe embryonic development. After 48 h, six cleaving embryos had developed to at least the two-cell stage, while one had arrested at the pronuclear stage. At 72 h, the cleaving embryos showed further development to the four- to six-cell stage. They were then transferred into the uterus. After 3 weeks a clinical pregnancy was established in one patient [beta-human chorionic gonadotrophin (beta HCG) concentration was 2100 UI]. At 16 weeks of gestation, chromosomic analysis was performed, which confirmed the presence of a fetus with normal karyotype. The pregnancy is ongoing.

Effects of anordiol, an antiestrogen, on the reproductive organs of the male rat.

Anordiol, an antiestrogen, was administered at doses of 2.5 and 10 mg/kg day-1 for 30 and 60 days to adult male rats. A significant decrease in serum LH, FSH, and testosterone levels occurred in the treated animals as compared to controls. Serum testosterone and LH levels decreased to about 15-35% of control value on day 15 of treatment and reached undetected levels thereafter. Serum FSH level also decreased to about 25-50% of control value by day 15 of treatment and remained at this level. Significant decrease in the weights of the tests and accessory reproductive organs occurred following anordiol treatment, while the body weights remained at pretreatment level. Histological examination of the tests revealed significant decrease in the diameter of the seminiferous tubules and in the number of germ cell elements. Spermatogenesis was arrested at the secondary spermatocyte stage. Leydig cells appeared atrophic and contained pyknotic nuclei. The epididymis, prostate, and seminal vesicle showed degenerative changes. The secretory activity of the glandular epithelium of the prostate gland appeared to be markedly reduced. In conclusion, anordiol acts by blocking gonadotropin production and/or release by the pituitary; thereby testosterone production by Leydig cells is not stimulated, causing spermatogenesis arrest.

Specific arrest of spermatogenesis caused by apoptotic cell death in transgenic mice.

The c-myc protooncogene has been implicated in the control of cell proliferation, differentiation and/or apoptosis in various cellular systems. However, the role of c-myc in germ cell lineage is largely unknown. We have produced transgenic mouse lines carrying the rat c-myc protooncogene under the control of human metallothionein promoter (hMT-c-myc). It was found that the male transgenic mice were sterile. In contrast, all of the female transgenic mice were completely fertile and transmitted the transgene to the next generation. However, male transgenic mice from the female transgenic founders were also found to be sterile. This sterility was due to a defect in spermatogenic cell differentiation, since virtually no sperm were seen within the seminiferous tubules or the cauda epididymis. Histological examination revealed that germ cell death occurred approximately 7 days after birth and, consequently, spermatogenesis was arrested at an early stage in meiotic division in the transgenic mice. Moreover, this germ cell death was found to be caused by apoptosis. We conclude that an excess level of c-myc expression in differentiating spermatogenic cells is responsible for the apoptotic death of germ cell, and that a decrease in c-myc level would be an obligatory step for the completion of normal spermatogenesis.

Effect of Immunization With Human SP‐10 in Male Rodents

Over the years immunocontraception has emerged as a promising modality. Theoretically it is possible to intercept fertility using a panel of antigens expressed along the entire pituitary, hypothalamus and gonadal axis. One such sperm antigen designated as SP-10 is in advanced stages of development. Its gene has been cloned by Wright et al. (Biol Reprod 1990; 42:693-701). It is envisaged that immunization with SP-10 would induce antisperm antibodies in females and hence interrupt fertility. However, the in vivo effect of SP-10 immunization has been assessed in male rodents with particular reference to spermatogenesis and effect of such immunization in various tissues. The SP-10 antigen was a generous gift from Dr. John Herr. A group of male Wistar rats and BALB/c mice were immunized with a total dose of 175 micrograms of SP-10 glutathione transferase fusion protein. Anti-SP-10 antibodies generated were detected by ELISA, immunofluorescence, flow cytometry and western blot assay. Histopathology of all the organs was conducted with particular reference to assess their effect on sperm maturation in testicular sections. All the animals immunized with SP-10 depicted a significant antibody response. DNA analysis by flow cytometry did not reveal any arrest of spermatogenesis, which was confirmed by histological studies. It is concluded that conventional immunization generating significant antibody titers does not induce arrest of spermatogenesis in male rodents.

The spermatogenetic process in Barbus longiceps, Capoeta damascina and their natural sterile hybrid (Teleostei, Cyprinidae)

Testicular ultrastructure was studied in Barbus longiceps, Capoeta damascina and their natural hybrid. The testes of these teleosts belong to the unrestricted or lobular type. Germ cell morphology is similar in the parental males. In the hybrid, spermatogenesis does not extend beyond the pachytene of the first meiotic division, probably due to the unsuccessful pairing of the homologous chromosomes. Hybrid testes are occupied mainly by degenerating primary spermatocytes, at the leptotene and pachytene stages. In both parents and the hybrid, Sertoli and Leydig cells are characterized by the presence of granular endoplasmic reticulum and of mitochondria with tubular cristae. Due to the arrest of spermatogenesis, the male germ cell protective barrier is absent in the hybrid. Germ cell nuclear size was measured by a computerized analysis system, using light‐microscopy images. In the parents and the hybrid, germ cells attain a uniform inter‐individual nuclear size when they reach the first meiotic prophase. The nuclear size of primary spermatocytes is similar among the three groups of fish, possibly reflecting their close genetic relationship.

Glutathione S-transferase-M1 'null' genotype and alcohol-induced disorders of human spermatogenesis.

The association between alcohol-induced disorders of human spermatogenesis and glutathione S-transferase-M1 genotype was investigated in an autopsy study comprising 271 subjects, including interviews with relatives or close acquaintances on the alcohol consumption of the deceased. Of the 50 moderate drinking men (reported mean daily alcohol consumption < 40 g), 21 (42.0%) had normal spermatogenesis, whereas 24 men (48.0%) had partial, and five (10.0%) complete arrest of spermatogenesis. Of the 21 men with normal spermatogenesis, nine (42.9%) had GST M1 'null' genotype, while this genotype was found in 13 (44.8%) of the 29 men with partial or complete spermatogenic arrest. Of 212 heavy-drinking men (reported mean daily alcohol consumption > 80 g), only 45 (21.2%) had normal spermatogenesis, whereas 77 (36.3%) had partial spermatogenic arrest. Complete arrest of spermatogenesis was found in 81 men (38.2%) and nine men had Sertoli-cell-only syndrome (4.2%). Of the 45 heavy drinkers with normal spermatogenesis, 27 (60%) men had GST M1 'null' genotype (OR 2.7 with 95% confidence intervals: 1.0-4.0, when compared to those with disorders of spermatogenesis). The frequency of GST M1 'null' genotype in heavy drinkers with normal spermatogenesis also differed from that of corresponding moderate drinkers, whereas the frequency of GST M1 'null' genotype in heavy drinkers with disorders of spermatogenesis was similar to moderate drinkers with or without disorders of spermatogenesis. The finding that > 20% of men in the heavy-drinking group had normal spermatogenesis suggests individual variations in sensitivity to alcohol-induced disorders of this process. Heavy drinkers with GST M1 'null' genotype were slightly less prone to develop disorders of spermatogenesis. Thus, the GST M1 locus may be associated with susceptibility to develop alcohol-induced disorders of spermatogenesis.

Antifertility effects of an LHRH agonist in male mice

<h2>Abstract</h2> This study was designed to investigate the effects of repeatedhigh doses of an LHRH agonist on Swiss porton mouse seminiferous epithelium. Seminiferous epithelium showed more pronounced degenerative effects at the higher dose (1000 μg/kg wt/day) of the drug, with arrest of spermatogenesis at all stages of differentiation; effects on spermatogenesis become more evident after pachytene spermatocyte stage. The decrease in the testis-specific enzyme LDH-X is accounted for by the decrease in the number of cells o f gametogenic origin. Although complete azoospermia was not observed, acute inhibition of motility of spermatozoa may account for severely decreased fertility rates after mating. However, reduced fertility rates due to decreased libido as a consequence of diminished testosterone levels cannot be discounted.

Antifertility efects of an LHRHagonist in male mice

This study was designed to investigate the effects of repeatedhigh doses of an LHRH agonist on Swiss porton mouse seminiferous epithelium. Seminiferous epithelium showed more pronounced degenerative effects at the higher dose (1000 μg/kg wt/day) of the drug, with arrest of spermatogenesis at all stages of differentiation; effects on spermatogenesis become more evident after pachytene spermatocyte stage. The decrease in the testis-specific enzyme LDH-X is accounted for by the decrease in the number of cells o f gametogenic origin. Although complete azoospermia was not observed, acute inhibition of motility of spermatozoa may account for severely decreased fertility rates after mating. However, reduced fertility rates due to decreased libido as a consequence of diminished testosterone levels cannot be discounted.

Effects of pineal indoles and parachlorophenylalanine on seasonal reproduction in the pigeon

The effect of melatonin, methoxytryptophol (ML), methoxytryptamine (MT) and parachlorophenylalanine (p-CPA) on the mass and histology of the testes and the adrenal and thyroid glands and on serum thyroid hormone levels have been studied in the recrudescent phase of the feral pigeon Columba livia. All the pineal indoles showed a common anti-gonadal effect, resulting in the arrest of spermatogenesis and the degeneration of germ cells. Treatment with melatonin resulted in adreno-cortical enlargement and medullary hypertrophy, whereas ML, MT and p-CPA induced medullary enlargement and hypertrophy without having much influence on the cortex. Treatment with melatonin and ML brought about colloid retention in the thyroid follicles, while MT and p-CPA induced colloid depletion and hypertrophy of the follicular epithelium. From the present study, it can be concluded that both pineal indoles and p-CPA induce testicular regression in the breeding phase but do so by different mechanisms.

Fertility with testicular sperm extraction and intracytoplasmic sperm injection in non-obstructive azoospermic men

In non-obstructive azoospermia spermatozoa can usually only be isolated from the testicles, and thus the most promising treatment model is testicular sperm extraction (TESE). Hormone concentrations, testicular volume determinations and testicular biopsy results are not uniform enough to select potential candidates for successful TESE and intracytoplasmic sperm injection (ICSI) approaches in advance. The aim of this study was to assess the efficacy of using ICSI with testicular spermatozoa in cases of non-obstructive azoospermia and to compare the inclusion criteria and sperm existence in the testicles in sperm obtainable and non-obtainable groups. All men showed either complete or incomplete (n = 14) maturation arrest in spermatogenesis, severe hypospermatogenesis (n = 10) or Sertoli cell-only syndrome (n = 5) in their testicular biopsies. Only 14 out of a total of 29 men provided enough spermatozoa for the ICSI procedure, while no spermatozoa were found in the testicular samples of the remaining 15 men. Out of 123 oocytes obtained from 14 females, 101 were injected with the husbands' testicular sperm cells. Total fertilization failure was observed in three cases. Of 39 oocytes fertilized, 38 cleaved. The fertilization and cleavage rates were 38.6 and 97.4% respectively. The pregnancy rate was 20.7% per initiated cycle. In the group from whom spermatozoa were obtainable, the pregnancy rate was 42.9% per initiated cycle and 54.5% per embryo transfer. A total of six pregnancies were achieved, of which two were twins and four were singletons. One singleton pregnancy resulted in abortion in the first trimester. There was no statistical difference concerning the serum follicle stimulating hormone concentration, testicular volume and biopsy results in groups in which spermatozoa were obtainable or not. In conclusion, although the association of TESE with ICSI obtained pregnancies for some patients with non-obstructive azoospermia, further studies are needed to determine the inclusion criteria for successful TESE.

CREM: a transcriptional master switch during the spermatogenesis differentiation program.

Spermatogenesis is a complex differentiation process under the hormonal control of the hypothalamic-pituitary axis. The CREM gene encodes activators and repressors of cAMP-mediated gene transcription. The transcript corresponding to the activator isoform CREMtau is found at high levels in pachytene spermatocytes onwards. The CREMtau protein, however, is present only in post-meiotic spermatids where it activates the transcription of testis-specific genes, such as the protamines and transition proteins. Mice in which the CREM gene has been inactivated by homologous recombination have been generated. Homozygous male mutant mice are sterile and produce no spermatozoa. Histological analysis of the seminiferous tubules reveal a complete arrest of spermatogenesis at the first step of spermiogenesis. CREM deficiency results in the lack of post-meiotic gene expression and a ten-fold increase in apoptotic germ cells. These results demonstrate the essential role of CREM in spermatogenesis and are reminiscent of some cases of male infertility.

Lesions in the bed nucleus of the stria terminalis, but not in the lateral septum, inhibit short-photoperiod-induced testicular regression in Syrian hamsters

The transfer of adult male hamsters from long days (LD) to short days (SD) (i.e. < 12 h of light per day) typically results in marked testicular regression and a decline in plasma testosterone concentrations. To help disclose key brain regions responsible for mediating this photoperiodic response male hamsters received either chemical (i.e. N-methyl- d-aspartate; NMDA) or radiofrequency current lesions in the bed nucleus of the stria terminalis (BNST), and were then exposed to SD for 15 or 12 weeks, respectively. Although body weights were similar between sham-lesioned controls and the NMDA-lesioned hamsters, the latter showed a significant attenuation of testicular regression; additionally, their plasma testosterone concentrations remained at typical LD levels. When radiofrequency current-lesioned hamsters were transferred from LD to SD they also failed to show significant signs of testicular regression, nor a decline in plasma testosterone concentrations, nor a complete arrest of spermatogenesis. In contrast, sham-lesioned controls or hamsters that were lesioned dorsally to the BNST at a site primarily involving the lateral septum all showed the expected degree of testicular regression, a decline in plasma testosterone concentrations, and complete arrest of spermatogenesis; body weights were similar in all of the experimental group. Taken together, these findings suggest that the BNST, a brain area traditionally not associated with reproductive function, may play an important role in mediating photoperiodic information to the neural circuits that control the reproductive axis.

Inverse relationship between testicular proliferation and apoptosis in mammalian seasonal breeders

Seasonal cycles of testicular activity occur in many mammals and can include transitions between total arrest and recrudescence of spermatogenesis. We hypothesize that involution and reactivation of testis result from two antagonistic processes, proliferation and programmed cell death (apoptosis), which are activated at different times. To test this hypothesis, quantitative measurements of both proliferation-specific marker and apoptotic produced nucleosomes have been compared with sperm and testosterone production in testes from adult roe deer during breeding and non-breeding seasons (May to September). Testes of brown hare were included from periods of testes regression (June to August) and recrudescence (November to December). The highest testicular weights in roe deer were found in the rutting period from late July to early August (27.25 ± 8.56 g), corresponding with the highest number of testicular sperm/g parenchyma. The peak of sperm production coincided with a peak in testosterone concentration (1.19 ± 0.53 μg/g testis). The maximum level of proliferation-specific marker was also found during the breeding season (98.6 ± 58.2 U/g testis in comparison to 20.1 ± 22.0 U/g in the prerutting period). In contrast, the most significant apoptosis was observed in the nonbreeding season than the breeding period (71.11 ± 5.79 U/mg testis and 18.88 ± 6.79 U/mg, respectively). Testicular proliferation was low in the brown hare (0.061 ± 0.062 U/g) during involution of the testes. It was newly activated in November and December (0.85 ± 0.33 U/g), preceding the increase in testicular volume. Testosterone production increased in conjunction with testicular proliferation. At this time, testicular apoptosis was significantly lower (14.16 ± 2.12 U/mg testis) than during the period of pronounced testicular regression (30.16 ± 19.95 U/g). These results suggest that regulation of seasonal testicular activity is characterized by an inverse relationship of proliferation and apoptosis.

Reproductive function in men following exposure to chemical warfare with sulphur mustard.

To investigate the acute and chronic effects in young men of exposure to chemical warfare containing mustards, the time course of changes in serum concentrations of total and free testosterone, dehydroepiandrosterone (DS), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and prolactin was evaluated in 16 men in the first three months and testicular function in 42 men one to three years after injury. Serum total and free testosterone and DS were markedly decreased in the first five weeks after exposure. The lowest values were: total testosterone 237 +/- 165, free testosterone 22.5 +/- 9.7, DS 39 +/- 25; as compared to controls: total testosterone 773 +/- 245 ng/dl, free testosterone 35.5 +/- 11.2 pg/ml and DS 207 +/- 37 micrograms/dl. FSH, LH, prolactin and 17 alpha-OH progesterone were normal in the first week. The response to GnRH was subnormal in four of five subjects. LH increased by the third and FSH and prolactin by the fifth week. All hormone levels had returned to normal by twelfth week after exposure. In 28 of 42 men seen one to three years following injury, sperm count was below 30 million cells/ml, and FSH was increased as compared to men with sperm above 60 million cells/ml. Testicular biopsy showed complete or relative arrest of spermatogenesis. This study demonstrates that the exposure to sulphur mustard results in very low androgen levels and hypo-responsiveness to GnRH in the first five weeks and normalization by the twelfth week after injury. However, side effects of mustard on sperm cells persist and may cause defective spermatogenesis years after exposure.

The distribution pattern of cytokeratin and vimentin immunoreactivity in testicular biopsies of infertile men

Testicular biopsies of infertile patients are often characterized by a mixed atrophy, in which different types of spermatogenic lesions are found in adjacent tubules. In order to evaluate a possible involvement of the state of differentiation of the Sertoli cells, the distribution pattern of cytokeratin and vimentin intermediate filaments within the seminiferous epithelium of 228 biopsy specimens with normal spermatogenesis (n = 10), mixed atrophy (n = 206) or Sertoli Cell Only Syndrome (n = 12) were investigated by means of immunohistochemical techniques. Sertoli cells were regularly found to show vimentin expression in tubules with normal spermatogenesis as well as in tubules with any kind of spermatogenic impairment including SCO. Cytokeratin expression as a marker showing lack of differentiation was common in Sertoli cells of tubules with arrest of spermatogenesis at the level of spermatogonia, and was occasionally associated with arrest at the level of primary spermatocytes or with SCO. Ultrastructural examination of tubules with spermatogonial arrest revealed Sertoli cells with features of typical fetal or prepubertal Sertoli cells, such as round to ovoid nuclei without indentations, stacks of rough ER and spot desmosomes. These data suggest that spermatogenic arrest at the level of spermatogonia might be due to functional impairment of the associated Sertoli cells, which have maintained or regained an undifferentiated state and are not able to initiate or trigger the process of spermatogonial differentiation.

Ultrastructure of the Hinny (Equus asinus × Equus caballus) Seminiferous Epithelium

The gonads and the germinative cells of 3 male hinnies were studied with light and transmission electron microscopy with the aim to observe the development of germ cells and verify the morphological modifications due to the hybridization. The hinny seminiferous epithelium presented Sertoli cells and spermatogonia with normal features and anomalous spermatocytes I. The other cells from the spermatogenic sequence were not seen. Most of the alterations began to occur in the cytes I, which presented nuclear vacuolization and deposits of amorphous material between the carioteca and the nuclear lamina, forming vesicles, or exaggerated chromatin condensation, resulting in pyknosis. In the cytoplasm vacuolization was also observed, besides organelle destruction. The arrest of meiosis due to lock of chromosome homologies leads to germinative cell degeneration and, therefore, the spermatogenesis arrest. This fact causes a profound alteration in the seminiferous epithelium morphology in comparison with the parental species.

Spermatogenic arrest and 'Sertoli cell-only' syndrome--common alcohol-induced disorders of the human testis.

The effect of alcohol on spermatogenesis and morphometric analysis of the human testis was investigated in a prospective autopsy study, with detailed alcohol-use reports from relatives or friends of the deceased. The autopsy series comprised non-alcoholic controls (daily intake < 10 g; n = 32) and heavy-drinkers (n = 44) with an intake of > 80 g per day. Of the controls, 26 (81.3%) men showed normal spermatogenesis, and six (18.7%) partial spermatogenic arrest. Of the heavy drinkers, only 16 (36.4%) had normal spermatogenesis (p < 0.001), while 23 (52.3%) showed partial or complete spermatogenic arrest (p < 0.001) and five had Sertoli cell-only (SCO) syndrome (p < 0.05). The mean testicular weight of heavy-drinkers was slightly (p < 0.05) lower than in the controls. Compared to men with normal spermatogenesis, testicular weight was slightly lower both in controls and heavy-drinkers with spermatogenic arrest, and was significantly (p < 0.01) lower in heavy-drinking men with SCO syndrome. Spermatogenic arrest was not correlated with fatty liver or cirrhosis of the liver, whereas four of the five men with SCO syndrome exhibited a fatty liver. Thus, our results suggest that the most common alcohol-related pathological change in the testes is probably reversible arrest of spermatogenesis. Furthermore, we suggest that many heavy social drinkers may suffer from self-inflicted infertility, as one tenth of heavy-drinkers in our study had SCO syndrome.