[IMMUNOCYTOCHEMICAL ANALYSIS OF THE DISTURBANCES IN THE STRUCTURE OF SYNAPTONEMAL COMPLEXES IN SPERMATOCYTE NUCLEI IN MICE UNDER EXPOSURE TO ROCKET FUEL COMPONENT].

There was performed an assessment of genotoxic effects of rocket fuel component--unsymmetrical dimethylhydrazine (UDMH, heptyl)--on forming germ cells of male mice. Immunocytochemically there was studied the structure of meiotic nuclei at different times after the intraperitoneal administration of UDMH to male mice. There were revealed following types of disturbances of the structure of synaptonemal complexes (SCs) of meiotic chromosomes: single and multiple fragments of SCs associations of autosomes with a sex bivalent, atypical structure of the SCs with a frequency higher than the reference level. In addition, there were found the premature desinapsis of sex bivalents, the disorder offormation of the genital corpuscle and ring SCs. Established disorders in SCs of spermatocytes, analyzed at 38th day after the 10-days intoxication of animal by the component of rocket fuel, attest to the risk of permanent persistence of chromosomal abnormalities occurring in the pool of stem cells.

The current state of male hormonal contraception.

World population continues to grow at an unprecedented rate, doubling in a mere 50years to surpass the 7-billion milestone in 2011. This steep population growth exerts enormous pressure on the global environment. Despite the availability of numerous contraceptive choices for women, approximately half of all pregnancies are unintended and at least half of those are unwanted. Such statistics suggest that there is still a gap in contraceptive options for couples, particularly effective reversible contraceptives for men, who have few contraceptive choices. Male hormonal contraception has been an active area of research for almost 50years. The fundamental concept involves the use of exogenous hormones to suppress endogenous production of gonadotropins, testosterone, and downstream spermatogenesis. Testosterone-alone regimens are effective in many men but high dosing requirements and sub-optimal gonadotropin suppression in 10-30% of men limit their use. A number of novel combinations of testosterone and progestins have been shown to be more efficacious but still require further refinement in delivery systems and a clearer understanding of the potential short- and long-term side effects. Recently, synthetic androgens with both androgenic and progestogenic activity have been developed. These agents have the potential to be single-agent male hormonal contraceptives. Early studies of these compounds are encouraging and there is reason for optimism that these may provide safe, reversible, and reliable contraception for men in the near future.

Male contraception.

Clear evidence shows that many men and women would welcome new male methods of contraception, but none have become available. The hormonal approach is based on suppression of gonadotropins and thus of testicular function and spermatogenesis, and has been investigated for several decades. This approach can achieve sufficient suppression of spermatogenesis for effective contraception in most men, but not all; the basis for these men responding insufficiently is unclear. Alternatively, the non-hormonal approach is based on identifying specific processes in sperm development, maturation and function. A range of targets has been identified in animal models, and targeted effectively. This approach, however, remains in the pre-clinical domain at present. There are, therefore, grounds for considering that safe, effective and reversible methods of contraception for men can be developed.

Potential of triptolide in reproductive management of the house rat, Rattus rattus.

Mature and healthy male house rats, Rattus rattus (n= 160) were fed on bait (cracked wheat: powdered sugar, 98:2) containing different concentrations of triptolide (0.1, 0.05, 0.025 and 0%) for 7 and 14 days in no-choice and bi-choice feeding tests in the laboratory. The objective of the study was to record the antifertility affects of triptolide after 30 and 60 days of termination of treatment. Results revealed no significant effect of triptolide treatment on weights of testis, epididymis, seminal vesicles and prostate gland of rats. Overall, sperm motility, live sperm count, sperm density and sperm morphology in the cauda epididymal fluid were found to differ significantly (P≤ 0.05) between untreated and treated groups of rats. The major effect of triptolide on sperm morphology was in the form of sperm head tail separation, which was up to 56.0% in rats treated for 14 days in no-choice and autopsied after 30 days. A significant effect (P≤ 0.05) of triptolide treatment was observed on the histomorphology of the testis, which included a dose-dependent decrease in diameter of seminiferous tubules, thickness of germinal epithelium and numbers of various spermatogenic cells. Cell associations in the seminiferous epithelial cycle were poorly developed in rats ingesting medium (4.7-5.1 mg/100 g bw) and high doses (6.9-7.2 mg/100 g bw) of triptolide than rats ingesting low doses (1.8-2.3 mg/100 g bw) and untreated rats. The cell stages affected had not recovered fully within the 60 day period following triptolide withdrawal. The present study suggests the potential of triptolide in reproductive management of Rattus rattus.

Experimental endocrine manipulation by contraceptive regimen in the male marmoset (Callithrix jacchus).

Marmosets are used as preclinical model in reproductive research. In contrast to other primates, they display short gestation times rendering this species valid for exploration of effects on fertility. However, their peculiar endocrine regulation differs from a those of macaques and humans. We subjected male marmosets to previously clinically tested hormonal regimens that are known to effectively suppress spermatogenesis. Beside a control group, seven groups (each n=6) were investigated for different periods of up to 42 months: regimen I, (four groups) received testosterone undecanoate (TU) and norethisterone enanthate (NETE); regimen II, (two groups) received TU and NETE followed by NETE only; and regimen III, (one group) received NETE only. Testicular volume, cell ploidy and histology, endocrine changes and fertility were monitored weekly. TU and NETE and initial TU and NETE treatment followed by NETE failed to suppress spermatogenesis and fertility. Testicular volumes dropped, although spermatogenesis was only mildly affected; however, testicular cellular composition remained stable. Serum testosterone dropped when NETE was given alone but the animals remained fertile. Compared with controls, no significant changes were observed in sperm motility and fertility. Administration of TU and NETE affected testicular function only mildly, indicating that the regulatory role of chorionic gonadotrophin and testosterone on spermatogenesis is obviously limited and testicular function is maintained, although the endocrine axis is affected by the treatment. In conclusion, marmosets showed a different response to regimens of male contraception from macaques or men and have to be considered as a problematic model for preclinical trials of male hormonal contraception.

Reversible antispermatogenic and antisteroidogenic activities of Feronia limonia fruit pulp in adult male rats.

OBJECTIVE: To explore the antispermatogenic and testicular antisteroidogenic activities of Feronia limonia fruit pulp southern India. METHODS: Fourty Wistar male albino rats (Rattus norvegicus) were equally divided into four groups. Experimental groups were administered with the ethanolic extract of Feronia limonia (F. limoni) fruit pulp at doses of 250 and 500 mg/kg body weight once daily for 55 days. All treated rats had corresponding recovery groups. At the end of each treatment periods, various spermatological indices, tissue biochemicals and testicular enzymes levels were analysed. Blood profiles were also estimated. RESULTS: Compared with the control, the F. limonia fruit pulp at both dose levels did not decrease body weight, which were associated with decline in epididymal sperm count, motility, viability and increased percent of abnormal sperm. Further, F. limonia fruit pulp at 500 mg/kg body weight markedly reduced the epididymal and testicular protein content by 24.58% and 29.86%, respectively, as well as the glucose-6-phosphate dehydrogenase and Δ(5)-3ß-hydroxy steroid dehydrogenase) levels by 42.82% and 38.08%, respectively, while a significant elevation was observed in testicular cholesterol and ascorbic acid content. A gradual recovery of all parameters was observed after 55 days of treatment withdrawal. No significant alterations in haematological indices were observed. CONCLUSIONS: The present findings indicate that F. limonia fruit pulp may have reversible antispermatogenic and antisteroidogenic properties, and could partially support the traditional use as male contraceptive.

Lonidamine affects testicular steroid hormones in immature mice.

The effects on the hypothalamus-pituitary-testicular axis of the well-known antispermatogenic drug lonidamine (LND) has not been elucidated so far. In the present study, the possible changes of the testicular steroid hormones were evaluated in immature mice for a better characterization of the LND adverse effects both in its use as antitumoral agent and male contraceptive. Male CD1 mice were orally treated on postnatal day 28 (PND28) with LND single doses (0 or 100 mg/kg b.w.) and euthanized every 24 h from PND29 to PND32, on PND35 and on PND42 (1 and 2 weeks after the administration, respectively). Severe testicular effects were evidenced in the LND treated groups, including: a) significant testis weight increase, 24 h and 48 h after dosing; b) sperm head counts decrease (more than 50% of the control) on PND29-32; c) damage of the tubule morphology primarily on the Sertoli cell structure and germ cell exfoliation. All these reproductive endpoints were recovered on PND42. At the same time, a significant impairment of the testicular steroid balance was observed in the treated mice, as evidenced by the decrease of testosterone (T) and androstenedione (ADIONE) and the increase of 17OH-progesterone (17OH-P4) on the first days after dosing, while the testicular content of 17beta-estradiol (E2) was unchanged. The hormonal balance was not completely restored afterwards, as levels of T, ADIONE and 17OH-P4 tended to be higher in the treated mice than in the controls, on PND35 and PND42. These data showed for the first time that LND affects intratesticular steroids in experimental animals. However further data are needed both to elucidate the mechanism responsible for the impairment of these metabolic pathways and to understand if the androgens decrease observed after LND administration could be partially involved in the testicular damage.

The acceptability of an injectable, once-a-month male contraceptive in China.

PURPOSE: An acceptability study of an injectable preparation of the synthetic steroid testosterone undecanoate as a once-a-month male contraceptive method was carried out concurrently with, but independently from, a clinical safety and efficacy trial of this preparation in China, from 1997 to 1999. METHOD: Three hundred eight men, the entire group of volunteers enrolled in the clinical trial, were interviewed using a structured questionnaire. In addition, 24 sessions of focus group discussions and 54 in-depth interviews were conducted with a broad range of stakeholders, including men enrolled in the trial and their wives, potential users, service providers, principal investigators of the six participating clinical trial centers, provincial and national policy makers, and experts engaged in research and development of male methods of contraception. RESULTS: Overall, men found the regimen to be acceptable, and most reported no change or an improvement in their well-being as a result of participating in the clinical study. The frequency of the injections, monthly semen analyses and the need to use another contraceptive method during the period of sperm suppression were reported inconveniences of the trial. CONCLUSION: Further research is needed to assess the long-term safety, continuation rates, satisfaction among users and issues related to service delivery.

Antispermatogenic, antiandrogenic activities of Albizia lebbeck (L.) Benth bark extract in male albino rats.

Methanolic extract of Albizia lebbeck bark when administered orally at the dose level of 100 mg/rat/day to male rats of proven fertility for 60 days did not cause any significant loss in their body weights but the weights of reproductive organs, i.e. testis, epididymides, seminal vesicle and ventral prostate were decreased in a significant manner when compared to controls. Sperm motility as well as sperm density were reduced significantly which resulted in reduction of male fertility by 100%. Marked decline in the germ cell population was noticed. Population of preleptotene, pachytene, secondary spermatocytes and step-19 spermatid were declined by 60.86%, 65.81%, 71.56% and 66.55%, respectively. Cross-sectional surface area of sertoli cells as well as the cells counts were found to be depleted significantly. Leydig cells nuclear area and number of mature Leydig cells were decreased by 60.03% and 51.56%, respectively. Serum testosterone levels showed significant reduction after A. lebbeck extract feeding. Oral administration of the extract did not affect red blood cell (RBC) and white blood cell (WBC) count, haemoglobin, haematocrit and glucose in the blood and cholesterol, protein, triglyceride and phospholipid in the serum. In conclusion, A. lebbeck bark extract administration arrests spermatogenesis in male rats without noticeable side effects.

Sublethal doses of malathion alter male reproductive parameters of Eisenia foetida / Malathion en dosis subletales altera los parámetros reproductivos masculinos de Eisenia foetida

Malathion es un insecticida organofosforado cuyo efecto agudo principal es la inhibición de la enzima acetilcolinesterasa. Este pesticida es usado ampliamente y se ha informado como dañino para la espermatogénesis de ratones. El objetivo de este trabajo fue evaluar el riesgo tóxico de malathion. Gusano de tierra Eisenia foetida (Annelida, Oligochaeta) se usó como modelo biológico y se analizaron testículos y espermatozoides de animales controles y tratados. Se usaron gusanos de tierra con clitelo desarrollado, los cuales fueron aspersados con dosis sub letales de 0, 80, 150, 300 y 600 mg de malathion por kilogramo de tierra (LD50 = 880 mg/kg de tierra seca). A los grupos controles se les agregó solo agua destilada. Cada grupo se analizó a los 1, 5, 15 y 30 días post tratamiento. Los resultados observados en los animales tratados indican un alza significativa en el número de espermatozoides a los 1 y 5 días después del tratamiento, seguido por una disminución espermática entre los 15 y 30 días. El uso de naranja de acridina mostró un aumento significativo de espermatozoides metacromáticos anormales en animales tratados (fluorescencia roja). La histología testicular en animales tratados mostró desorganización del tejido y vacuolización, con la presencia de núcleos pequeños e hipercromáticos, indicativo de posible apoptosis. Además, malathion causó contracción corporal caracterizada por la cola enrollada. Se concluye que malathion provoca una alteración significativa en el recuento y en la calidad espermática, en la histología testicular y en la morfología corporal de Eisenia foetida. Este modelo biológico resulta ser excelente para supervisar el daño citotóxico de pesticidas organofosaforados.

Male hormonal contraception: suppression of spermatogenesis by injectable testosterone undecanoate alone or with levonorgestrel implants in chinese men.

Monthly injections of testosterone undecanoate (TU) act as a male contraceptive by reversibly suppressing spermatogenesis to azoospermia or severe oligoazoospermia in 95% of Chinese men. In 5% of Chinese men, however, monthly TU administered alone fails to suppress spermatogenesis into contraceptive ranges, or sperm "rebound," leading to occurrences of pregnancy during treatment. Since combinations of progestins and androgens are associated with greater degrees of sperm suppression in white men, we hypothesized that the combination of TU and the progestin levonorgestrel (LNG) would result in improved spermatogenic suppression in Chinese men. Sixty-two healthy Chinese men were randomly assigned to one of the following 3 regimens: group I (n = 21) received 4 LNG rods (75 mg each), which were followed 4 weeks later by 500 mg of TU by intra-muscular (IM) injection every 8 weeks for 24 weeks; group II (n = 20) received 4 LNG implants, which were followed 4 weeks later by 1000 mg of TU by IM injection every 8 weeks for 24 weeks; and group III (n = 21) received TU 1000 mg by IM injection every 8 weeks for 24 weeks. Sperm counts, serum testosterone (T), luteinizing hormone, follicle-stimulating hormone, and LNG were measured every 2 weeks before, during, and after treatment. During treatment, group II demonstrated a trend toward a greater attainment of azoospermia than groups I and III (90% vs 62% [group I] vs 67% [group III]; P =.09). Attainments of either azoospermia or oligozoospermia (sperm density, <3 x 10(6)/mL) were 95%, 100%, and 86% for groups I, II, and III, respectively (P >.05 for comparisons between groups). Spermatogenesis in all subjects returned to the normal range after the implants were removed. No serious adverse events and no significant changes in serum chemistry occurred during the study. These results demonstrate that the combination of IM injections of high-dose TU every 2 months and LNG implants is associated with marked suppression of spermatogenesis in Chinese men. The combination of high-dose TU every 2 months and LNG implants is a promising candidate for future large-scale efficacy studies of hormonal male contraception in Chinese men.

A study of microemulsion systems for transdermal delivery of triptolide.

Triptolide possesses immunosuppressive, anti-fertility and anti-cancer activities. Due to its severe toxicity, microemulsions with controlled, sustained and prolonged delivery of triptolide via a transdermal route are expected to reduce its adverse side effects. The purpose of the present study was to investigate the microemulsions for transdermal delivery of triptolide. The pseudo-ternary phase diagrams were developed and various microemulsion formulations were prepared using oleic acid as an oil, Tween 80 as a surfactant and propylene glycol as a cosurfactant. The droplet size of microemulsions was characterized by photocorrelation spectroscopy. The transdermal ability of triptolide from microemulsions was evaluated in vitro using Franz diffusion cells fitted with mouse skins and triptolide was analyzed by high-performance liquid chromatography. The effect of menthol as a permeation enhancer, and the loading dose of triptolide in microemulsions on the permeation rate were also evaluated. The triptolide-loaded microemulsions showed an enhanced in vitro permeation through mouse skins compared to an aqueous solution of 20% propylene glycol containing 0.025% triptolide. The permeation of microemulsions accorded with the Fick's first diffusion law. No obvious skin irritation was observed for the studied microemulsion ME6, but the aqueous solution of 20% propylene glycol containing 0.025% triptolide revealed the significant skin irritation. The results indicate that the studied microemulsion systems, especially ME6, may be promising vehicles for the transdermal delivery of triptolide.

2,5-hexanedione and carbendazim coexposure synergistically disrupts rat spermatogenesis despite opposing molecular effects on microtubules.

2,5-Hexanedione (2,5-HD), a taxol-like promoter of microtubule assembly, and carbendazim (CBZ), a colchicine-like inhibitor of microtubule assembly, are two environmental testicular toxicants that target and disrupt microtubule function in Sertoli cells. At the molecular level, these two toxicants have opposite effects on microtubule assembly, yet they share the common physiologic effect of inhibiting microtubule-dependent functions of Sertoli cells. By studying a combined exposure to 2,5-HD and CBZ, we sought to determine whether CBZ would antagonize or exacerbate the effects of an initial 2,5-HD exposure. In vitro, 2,5-HD-treated tubulin had a decreased lag time and an increased maximal velocity of microtubule assembly. These 2,5-HD-induced in vitro alterations in microtubule assembly were normalized by CBZ exposure. In vivo, adult male rats were exposed to a 1% solution of 2,5-HD in the drinking water for 2.5 weeks. CBZ was administered by gavage (200 mg/kg body weight) at the same time as unilateral surgical ligation of the efferent ducts, 24 h before evaluation of the testis. Measures of testicular effect (testis weight, histopathologic changes [sloughing and vacuolization], and seminiferous tubule diameters) were all significantly altered with combined exposure. The testicular effects in the combined exposure group were either different (seminiferous tubule diameters), additive (% vacuolization), or greater than additive (% sloughing) compared to the effects of the individual toxicant exposure groups referenced to the controls. Therefore, CBZ coexposure does not antagonize the effects of an initial 2,5-HD exposure, as might be expected if their molecular effects on microtubule assembly were solely responsible for their combined toxicity; instead, 2,5-HD and CBZ act together to exacerbate the testicular injury.

Recent advances in hormonal male contraception.

Hormones inhibit fertility in men by suppressing sperm production. Testosterone-enanthate induced azoospermia has proven to provide optimal contraceptive protection. Preliminary studies have shown that testosterone alone or androgen-progestin combinations induce profound sperm suppression in the Eastern and white populations, respectively. Thus, these regimens may represent viable options for male contraception. New long-acting androgen formulations represent a major advancement in this field, allowing for the development of more acceptable and effective regimens.

Early testicular response to intraperitoneal administration of ethane dimethanesulphonate (EDS) in the goat (Capra hircus).

Early morphological changes in the goat testis after a single intraperitoneal injection of ethane dimethanesulphonate (EDS) were investigated using both light and electron microscopy. The compound was administered at two dose levels: 75 mg/kg and 25 mg/kg. While the former resulted in some deaths due to toxicity, the latter had no noticeable toxic effects on the animals. The testicular effects at both dose levels were similar. Six (6) days post-treatment, Leydig cells were refractory to EDS challenge but there was a marked disruption of spermatogenesis. These Leydig cells exhibited ovoid or irregularly round nuclei, abundant cytoplasm containing spherical, ovoid or elongate mitochondria and a preponderance of smooth endoplasmic reticulum typical of the normal cells. Lipid droplets were rare. In the seminiferous tubules germ and Sertoli cell degeneration was observed. Changes in the germ cells included: spermatogonial degeneration, condensed chromatin in leptotene spermatocytes and failure of chromatin re-organization resulting in the formation of clumps in the cells at the telophase stage of cell division (stage 4 of the seminiferous cycle). The nuclear envelope of primary spermatocytes showed marked irregularity and there was an overall reduction in cell size. There was peripheral re-distribution of chromatin in developing spermatids of stages 1, 2 and 5, often resulting in thick margination along the nucleolemma and leaving a pale nucleoplasm. An accompanying retention of maturation phase spermatids in stage 2 tubules was also observed. Sertoli cells exhibited extensive accumulation of intracytoplasmic vesicles, obscuring the rest of the organelles. Intercellular vacuoles also occurred within the epithelium. The results suggest that while EDS does not have any effect on goat Leydig cells, it causes severe disruption of the spermatogenic process. Furthermore, it is concluded from the results that the optimum dose in this species is 25 mg/kg.

Antifertility studies of Colebrookia oppositifolia leaf extract in male rats with special reference to testicular cell population dynamics.

Oral feeding of male rats with the ethanolic leaf extract of Colebrookia oppositifolia at dose levels of 100 and 200 mg/kg for 8-10 weeks did not cause body weight loss, while the weights of testes and epididymides were significantly decreased. Seminal vesicles and ventral prostate showed a significant reduction at the higher dose only. Treated animals showed a notable depression of spermatogenesis. Following 100 and 200 mg/kg extract feeding, the preleptotene spermatocytes were decreased by 46.5 and 39.8%, the secondary spermatocytes by 13.4 and 12.7%, the step-19 spermatids by 36.6 and 35.2%, and the mature Leydig cells by 31.2 and 39.5%, respectively. At both dose levels, the seminiferous tubule diameter, Leydig cells nuclear area and cytoplasmic area, as well as the cross-sectional surface area of Sertoli cells, were significantly reduced (P<0.001) when compared to controls. Reduced sperm count and motility resulted in 100% negative fertility at 200 mg/kg dose level. A significant fall in the total protein and sialic acid content and acid phosphatase enzyme activity of the testes, epididymides, seminal vesicle and ventral prostate, as well as in the glycogen content of testes, was also observed at both dose levels in comparison with controls.

Hormonal contraception in the male.

The hormonal approach to male contraception is based on the suppression of gonadotrophin secretion with secondary suppression of spermatogenesis. This can be achieved by administration of testosterone or other androgen alone, but combined administration with a progestogen or GnRH analogue allows the dose of testosterone to be reduced to physiological replacement doses. This approach has been investigated for many years but without identification of a regimen which results in sufficient suppression of spermatogenesis to provide ensured contraception in all men, safely and conveniently. The reasons for this are discussed, and recent developments towards a regimen that fulfills all these criteria are described. Crucial to development of any new product is that it will be used: surveys of both men and women indicate firmly positive attitudes towards a 'male pill'. There are, therefore, grounds for cautious optimism that the next decade may see the introduction of the first novel male contraceptive for several hundred years.

Reversible antispermatogenic effect of gossypol in langur monkeys (Presbytis entellus entellus).

The present investigation reports the antispermatogenic effect of the orally active highly purified gossypol acetic acid at 7.5 mg and 10 mg/day for 180 days in langur monkeys. The results revealed a dose-dependent response in semen analysis as well as testicular morphology. Uniform severe oligospermia was observed in the lower dose (7.5 mg) group, while azoospermia was observed in 2 out of 5 animals in the higher dose (10 mg) group and the remaining animals showed severe oligospermia. Scanning electron microscopy of spermatozoa revealed deleterious abnormalities in the head and midpiece. Testicular morphology revealed a decrease in the seminiferous tubule diameter and arrest of spermatogenesis. The lower dose group had a germ cell population up to primary spermatocytes while the higher dose group had only Sertoli cells and spermatogonia. Withdrawal of treatment for 180 days led to the recovery of all the parameters studied, to normalcy.

Triptolide: a potential male contraceptive.

The antifertility effect of triptolide and other related compounds, isolated from Tripterygium wilfordii, has been demonstrated in male rats. The exact sites and mechanism of action of triptolide remain unknown. Our objectives were to determine whether triptolide at selected dose levels that induce infertility has any detrimental effects on the testes and to determine the sites and the possible mechanisms of its action. Groups of six adult male Sprague-Dawley rats were given oral administration of either vehicle (control group) or triptolide (50 or 100 microg/kg body weight) daily for 35 or 70 days. Body weight gain was normal in all treated groups. All six rats treated with a high dosage of triptolide were infertile during the second (63-70 days) mating trial. A lower dose (50 microg) of triptolide gave intermediate fertility values. Plasma levels of luteinizing hormone, follicle-stimulating hormone, testosterone, and intratesticular testosterone were not significantly different between control and triptolide-treated groups. Cauda epididymal sperm content was decreased by 68% and the motility, which averaged 58.2% in the control rat, was reduced to almost zero. No effects of triptolide were observed on testis and accessory organs weight, volumes of tubular lumen and the total Leydig cells, tubule diameter, and the number of Sertoli cells, spermatogonia, preleptotene (PL), and pachytene (P) spermatocytes. There were, however, modest but significant decreases in tubule volume and the number of round spermatids at stages VII-VIII. No changes in the germ cell apoptotic index measured at stages VII-VIII and XIV-I were noted between controls and rats rendered infertile with a high dose of triptolide. Thus, triptolide, at a dose level that induces complete infertility in the adult rats, has minimal adverse effects on the testes and acts primarily on the epididymal sperm making triptolide an attractive lead as a post-testicular male contraceptive.