Granulocytic myeloid-derived suppressor cells inhibit T follicular helper cells during experimental Schistosoma japonicum infection.

BACKGROUND: CD4+ T helper (Th) cells play critical roles in both host humoral and cellular immunity against parasitic infection and in the immunopathology of schistosomiasis. T follicular helper (Tfh) cells are a specialized subset of Th cells involved in immunity against infectious diseases. However, the role of Tfh cells in schistosome infection is not fully understood. In this study, the dynamics and roles of Tfh cell regulation were examined. We demonstrated that granulocytic myeloid-derived suppressor cells (G-MDSC) can suppress the proliferation of Tfh cells. METHODS: The levels of Tfh cells and two other Th cells (Th1, Th2) were quantitated at different Schistosoma japonicum infection times (0,3, 5, 8, 13 weeks) using flow cytometry. The proliferation of Tfh cells stimulated by soluble egg antigen (SEA) and soluble worm antigen (SWA) in vivo and in vitro were analyzed. Tfh cells were co-cultured with MDSC to detect the proliferation of Tfh cells labelled by 5(6)-carboxyfluorescein diacetate N-succinimidyl ester. We dynamically monitored the expression of programmed cell death protein 1 (PD-1) on the surface of Tfh cells and programmed cell death ligand 1 (PD-L1) on the surface of MDSC at different infection times (0, 3, 5, 8 weeks). Naïve CD4+ T cells (in Tfh cell differentiation) were co-cultured with G-MDSC or monocytic MDSC in the presence, or in the absence, of PD-L1 blocking antibody. RESULTS: The proportion of Tfh cells among CD4+ T cells increased gradually with time of S. japonicum infection, reaching a peak at 8 weeks, after which it decreased gradually. Both SEA and SWA caused an increase in Tfh cells in vitro and in vivo. It was found that MDSC can suppress the proliferation of Tfh cells. The expression of PD-1 on Tfh cells and PD-L1 from MDSC cells increased with prolongation of the infection cycle. G-MDSC might regulate Tfh cells through the PD-1/PD-L1 pathway. CONCLUSIONS: The reported study not only reveals the dynamics of Tfh cell regulation during S. japonicum infection, but also provides evidence that G-MDSC may regulate Tfh cells by PD-1/PD-L1. This study provides strong evidence for the important role of Tfh cells in the immune response to S. japonicum infection.

Schistosome eggs stimulate reactive oxygen species production to enhance M2 macrophage differentiation and promote hepatic pathology in schistosomiasis.

Schistosomiasis is a neglected tropical disease of public health concern. The most devastating pathology in schistosomiasis japonica and mansoni is mainly attributed to the egg-induced granulomatous response and secondary fibrosis in host liver, which may lead to portal hypertension or even death of the host. Schistosome eggs induce M2 macrophages-rich granulomas and these M2 macrophages play critical roles in the maintenance of granuloma and subsequent fibrosis. Reactive oxygen species (ROS), which are highly produced by stimulated macrophages during infection and necessary for the differentiation of M2 macrophages, are massively distributed around deposited eggs in the liver. However, whether ROS are induced by schistosome eggs to subsequently promote M2 macrophage differentiation, and the possible underlying mechanisms as well, remain to be clarified during S. japonicum infection. Herein, we observed that extensive expression of ROS in the liver of S. japonicum-infected mice. Injection of ROS inhibitor in infected mice resulted in reduced hepatic granulomatous responses and fibrosis. Further investigations revealed that inhibition of ROS production in S. japonicum-infected mice reduces the differentiation of M2, accompanied by increased M1 macrophage differentiation. Finally, we proved that S. japonicum egg antigens (SEA) induce a high level of ROS production via both nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) and mitochondria in macrophages. Our study may help to better understand the mechanism of schistosomiasis japonica-induced hepatic pathology and contribute to the development of potential therapeutic strategies by interfering with ROS production.

Toll-like receptor-2 regulates macrophage polarization induced by excretory-secretory antigens from Schistosoma japonicum eggs and promotes liver pathology in murine schistosomiasis.

Schistosomiasis is endemic to many regions of the world and affects approximately 200 million people. Conventional adaptive T cell responses are considered to be the primary contributors to the pathogenesis of Schistosoma japonicum infection, leading to liver granuloma and fibrosis. However, the functional polarization of macrophages and the associated underlying molecular mechanisms during the pathogenesis of schistosomiasis remains unknown. In the present study, we found that excretory-secretory (ES) antigens derived from S. japonicum eggs can activate macrophages, which exhibit an M2b polarization. Furthermore, ES antigen-induced M2b polarization was found to be dependent on enhanced NF-κB signaling mediated by the MyD88/MAPK pathway in a TLR2-dependent manner. In addition, the cytokine profile of the liver macrophages from wild-type-infected mice are quite distinct from those found in TLR2 knockout-infected mice by quantitative PCR analysis. More importantly, the size of granuloma and the severity of the fibrosis in the livers of TLR2-/- mice were significantly reduced compared to that in WT mice. Our findings reveal a novel role for M2b polarization in the pathogenesis of schistosome infection.

[Relation between ICOS signaling and Th9 cell polarization in mice infected with Schistosoma japonicum].

OBJECTIVE: To detect the expression level of ICOS on Th9 cells in mice infected with Schistosoma japonicum, and investigate the relation between ICOS signaling and Th9 cell polarization. METHODS: Twenty-five mice with S. japonicum infection were used as models. IL-9+cells in CD4+ T cells and ICOS+ cells in Th9 cells of the mice were detected by flow cytometry 0, 4, 7, 9 weeks and 12 weeks after the infection. RESULTS: Compared with that 0 week after the infection, the proportion of Th9 cells in CD4+ T cells of the mice significantly increased 4, 7, 9, 12 weeks after the infection (all P < 0.05), and the proportion of ICOS+ cells in Th9 cells also markedly improved (P < 0.05). CONCLUSIONS: In S. japonicum infection, the ICOS signaling may have a regulatory effect on Th9 cell polarization.

Schistosoma japonicum IAP and Teg20 safeguard tegumental integrity by inhibiting cellular apoptosis.

Schistosomes are causative agents of human schistosomiasis, which is endemic in tropical and subtropical areas of the world. Adult schistosomes can survive in their final hosts for several decades, and they have evolved various strategies to overcome the host immune response. Consequently, understanding the mechanisms that regulate parasitic cell survival will open avenues for developing novel strategies against schistosomiasis. Our previous study suggested that an inhibitor of apoptosis protein in Schistosoma japonicum (SjIAP) may play important roles in parasitic survival and development. Here, we demonstrated that SjIAP can negatively regulate cellular apoptosis in S. japonicum by suppressing caspase activity. Immunohistochemistry analysis indicated that SjIAP ubiquitously expressed within the worm body including the tegument. Silencing of SjIAP expression via small interfering RNA led to destruction of the tegument integrity in schistosomes. We further used co-immunoprecipitation to identify interaction partners of SjIAP and revealed the tegument protein SjTeg-20 as a putative interacting partner of SjIAP. The interaction between SjIAP and SjTeg-20 was confirmed by a yeast two-hybrid (Y2H) assay. Moreover, results of a TUNEL assay, RNA interference, scanning and transmission electron microscopy, caspase assays, transcript profiling, and protein localization of both interacting molecules provided first evidence for an essential role of SjIAP and SjTeg-20 to maintain the structural integrity of the tegument by negatively regulating apoptosis. Taken together, our findings suggest that the cooperative activities of SjIAP and SjTeg-20 belong to the strategic inventory of S. japonicum ensuring survival in the hostile environment within the vasculature of the final host.

Praziquantel Targets M1 Macrophages and Ameliorates Splenomegaly in Chronic Schistosomiasis.

Splenomegaly is a common feature of many infectious diseases, including schistosomiasis japonica. However, the immunopathogenesis and the treatment of splenomegaly due to schistosomiasis have been largely neglected. Praziquantel (PZQ), a classical schistosomicide, has been demonstrated by us and others to have antifibrotic and anti-inflammatory activities against schistosomiasis. In this study, we investigated the effect of PZQ on alleviating the splenomegaly caused by Schistosoma japonicum infection in mice. The results showed that the number of macrophages, especially the number of M1 macrophages, was significantly increased in the enlarged spleens of infected mice (P < 0.001). After PZQ treatment for 4 weeks, the number of splenic macrophages, especially the number of M1 macrophages, was significantly reduced (P < 0.001) by the way of apoptosis, and another schistosomicide, mefloquine, had no effect either on the splenomegaly or on reducing the number of macrophages. Furthermore, by using the murine macrophage line RAW 264.7, we found that PZQ could inhibit the formation of the NLRP3 inflammasome and attenuate phagocytic activity in M1 macrophages. Thus, our studies suggest that PZQ plays a powerful role in ameliorating the splenomegaly caused by S. japonicum infection, which presents a new strategy for the therapy of splenomegaly resulting from other pathological conditions.

Transcriptional profiling of chronic clinical hepatic schistosomiasis japonica indicates reduced metabolism and immune responses.

Schistosomiasis is a significant cause of human morbidity and mortality. We performed a genome-wide transcriptional survey of liver biopsies obtained from Chinese patients with chronic schistosomiasis only, or chronic schistosomiasis with a current or past history of viral hepatitis B. Both disease groups were compared with patients with no prior history or indicators of any liver disease. Analysis showed in the main, downregulation in gene expression, particularly those involved in signal transduction via EIF2 signalling and mTOR signalling, as were genes associated with cellular remodelling. Focusing on immune associated pathways, genes were generally downregulated. However, a set of three genes associated with granulocytes, MMP7, CLDN7, CXCL6 were upregulated. Differential gene profiles unique to schistosomiasis included the gene Granulin which was decreased despite being generally considered a marker for liver disease, and IGBP2 which is associated with increased liver size, and was the most upregulated gene in schistosomiasis only patients, all of which presented with hepatomegaly. The unique features of gene expression, in conjunction with previous reports in the murine model of the cellular composition of granulomas, granuloma formation and recovery, provide an increased understanding of the molecular immunopathology and general physiological processes underlying hepatic schistosomiasis.

Magnetic affinity enzyme-linked immunoassay for diagnosis of Schistosomiasis japonicum in persons with low-intensity infection.

Most schistosome-endemic areas in China are characterized by low-intensity infections that are independent of prevalence. To establish an effective diagnostic method, we developed a magnetic affinity enzyme-linked immunoassay based on soluble egg antigens (SEA-MEIA) for diagnosing schistosomiasis in persons with low-intensity infection with Schistosoma japonicum by comparing it with a conventional enzyme-linked immunosorbent assay (ELISA). Our results showed that the SEA-MEIA had a higher sensitivity and greater precision in the diagnosis of low-intensity S. japonicum infections than the ELISA. In addition, when we used Pearson's correlation in associating SEA-MEIA with ELISA, a significant correlation existed between the two assays (r = 0.845, P < 0.001). Our data indicated that SEA-MEIA, with a higher sensitivity and greater ease of performance, would be valuable for diagnosis of schistosomiasis japonicum in persons with low-intensity infections.

Tim-2 up-regulation and galectin-9-Tim-3 pathway activation in Th2-biased response in Schistosoma japonicum infection in mice.

T cell immunoglobulin domain and mucin domain (Tim) family, a new gene that expresses on the surface of T cells, plays a critical role in regulation of T cells response. Previous data have shown that Tim-3 expressed on Th1 cells promotes itself apoptosis. Tim-2 is preferentially up-regulated during Th2 differentiation and functions as a potent costimulatory molecule for T-cell immunity. The present study aims to learn whether Tims are responsible for Th2-biased response evoked by Schistosoma japonicum infection. The expressions of Tim-2 and Tim-3 in spleen lymphocytes from S. japonicum-infected mice were examined, and the possible role of galectin-9-Tim-3 pathway in Th2-biased response triggered by schistosome infection was discussed. Our results showed that Tim-2 mRNAs were up-regulated in the spleen of schistosome-infected mice, which coincided with elevated IL-4 gene expression. Administration of galectin-9 significantly induced apoptosis of naïve spleen lymphocytes with down-regulation IFN-γexpression in vitro. Additionally, Tim-3-Fc fusion protein notably enhanced Th1 cells and decreased Th2 cells in vitro. Thus, we concluded that pro-apoptotic effects on Th1 population through galectin-9-Tim-3 pathway and the up-regulation of Tim-2 on Th2 cells might be critical to Th2-biased response of host with schistosomiasis japonica.

Metabolic alterations in the hamster co-infected with Schistosoma japonicum and Necator americanus.

Co-infection with hookworm and schistosomes is a common phenomenon in sub-Saharan Africa, as well as in parts of South America and southeast Asia. As a first step towards understanding the metabolic response of a hookworm-schistosome co-infection in humans, we investigated the metabolic consequences of co-infection in an animal model, using a nuclear magnetic resonance (NMR)-based metabolic profiling technique, combined with multivariate statistical analysis. Urine and serum samples were obtained from hamsters experimentally infected with 250 Necator americanus infective L(3) and 100 Schistosoma japonicum cercariae simultaneously. In the co-infection model, similar worm burdens were observed as reported for single infection models, whereas metabolic profiles of co-infection represented a combination of the altered metabolite profiles induced by single infections with these two parasites. Consistent differences in metabolic profiles between the co-infected and non-infected control hamsters were observed from 4 weeks p.i. onwards. The predominant metabolic alterations in co-infected hamsters consisted of depletion of amino acids, tricarboxylic acid cycle intermediates (e.g. citrate and succinate) and glucose. Moreover, alterations of a series of gut microbial-related metabolites, such as decreased levels of hippurate, 3-hydroxyphenylpropionic acid, 4-hydroxyphenylpropionic acid and trimethylamine-N-oxide, and increased concentrations of 4-cresol glucuronide and phenylacetylglycine were associated with co-infection. Our results provide a first step towards understanding the metabolic response of an animal host to multiple parasitic infections.

Impacts of dietary intake and helminth infection on diversity in growth among schoolchildren in rural south China: a four-year longitudinal study.

The authors carried out six transverse anthropometric, dietary, and parasitological surveys of 274 schoolchildren (138 boys and 136 girls), aged 10-12 years (in 2001), from the Dongting Lake region in rural South China from 2001 to 2005 to examine intra-population differences in growth. Compared to the Chinese references, the subject children were judged to be retarded in growth at the population level. Comparisons among tertiles classified by the extents of change in weight-for-age Z score from the first to the last survey revealed significant effects of dietary intakes and parasite infections. In particular, there were two observations for the high-tertile boys and girls, whose Z scores of height-for-age, weight-for-age and BMI-for-age in higher ages were similar to, or higher than, the Chinese references. First, their energy intakes were larger than those of mid- and low-tertile boys and girls but were only 80-88% of the recommended dietary allowances for Chinese. Second, they were characterized by high prevalence of Schistosoma japonicum at the first survey but nil from the second survey. In conclusion, there is a high possibility that the children, who are recognized as undernourished at the population level, are able to attain the Chinese standards by increase of energy intake to the level of 10% lower than the recommended allowance for Chinese and eradication of S. japonicum.

Th2 cytokines are associated with persistent hepatic fibrosis in human Schistosoma japonicum infection.

We conducted a prospective cohort study in Leyte, the Philippines, among 611 Schistosoma japonicum-infected participants 7-30 years old, all of whom were treated with praziquantel at baseline. To detect hepatic fibrosis, abdominal ultrasound was performed at baseline and 12 months after treatment. Stool for assessment of S. japonicum infection was collected at baseline and at 3, 6, 9, and 12 months after treatment. Cytokines (interleukin [IL]-4, IL-5, IL-10, IL-13, tumor necrosis factor- alpha , and interferon- gamma ) produced by peripheral-blood mononuclear cells in response to soluble worm antigen preparation (SWAP), soluble egg antigen (SEA), and control medium were measured once 4 weeks after treatment. IL-4 to SWAP and IL-10 to both SWAP and SEA were associated with the presence of baseline fibrosis after adjustment for potential confounding variables (P<.03, for all). In participants with fibrosis at baseline, IL-4 to SWAP and IL-5 and IL-13 to both SWAP and SEA were associated with persistent fibrosis at 12 months after treatment (P<.05, for all). Males showed consistently stronger T helper 2 (Th2) cytokine responses to both SWAP and SEA than did females (P<.02, for all). These results suggest an independent role for Th2-biased cytokine responses to S. japonicum antigens in persistent hepatic fibrosis and indicate that Th2 cytokines may contribute to the male-biased prevalence of fibrosis.

Nutritional status and serum cytokine profiles in children, adolescents, and young adults with Schistosoma japonicum-associated hepatic fibrosis, in Leyte, Philippines.

In a cross-sectional study of 641 Schistosoma japonicum-infected individuals in Leyte, Philippines, who were 7-30 years old, we determined the grade of hepatic fibrosis (HF) by ultrasound and used anthropometric measurements and hemoglobin levels to assess nutritional status. Serum levels of interleukin (IL)-1, IL-6, and IL-10; tumor-necrosis factor (TNF)-alpha; soluble TNF- alpha receptor I; and C-reactive protein (CRP) were measured to examine the association between these markers of inflammation and HF grade. HF was present in 8.9% of the cohort; the majority of cases were mild (grade I), and severe (grade II or grade III) cases occurred only in male individuals. Compared with individuals without HF, those with severe HF--and, to a lesser degree, those with mild HF--had a significantly lower body-mass index (BMI) and BMI z-score, a higher prevalence of anemia, and a higher level of CRP and were more likely to produce IL-6; furthermore, those with severe HF had a significantly higher level of IL-1, compared with those either without HF or with mild HF. These findings suggest that even mild HF is associated with nutritional morbidity and underscore the importance of early recognition and treatment. In addition, our data are consistent with the hypothesis that, by systemically increasing the levels of the proinflammatory cytokines IL-1 and IL-6, HF causes undernutrition and anemia.

Relationship between Schistosoma japonicum and nutritional status among children and young adults in Leyte, the Philippines.

The objectives of this study were 1) to provide more accurate estimates of the relationship between Schistosoma japonicum infection and both protein energy malnutrition (PEM) and anemia through better adjustment for potential confounders such as socioeconomic status (SES) and geo-helminth infections and 2) to assess the role of occult blood loss in mediating S. japonicum-associated anemia. We examined cross-sectionally 729 individuals (86.7% S. japonicum-infected and 13.3% S. japonicum-uninfected) aged 7-30 years in Leyte, The Philippines. The main outcome measures were height-for-age Z-score (HAZ), body-mass-index Z-score (BMIZ), triceps skinfold Z-score, hemoglobin, and fecal occult blood loss. Multivariate models were created to assess the relationship between S. japonicum infection and nutritional status after adjusting for age, gender, other helminths, and SES. After controlling for confounders, intensity of S. japonicum infection was inversely related to hemoglobin in all age groups (P < 0.0001) and HAZ among children

Duplex Doppler ultrasound of hepatic Schistosomiasis japonica: a study of 47 patients.

This study describes the ultrasound (US) appearances of the liver with hepatic schistosomiasis japonica (HSJ), and studies the portal hemodynamics in 47 patients with HSJ using duplex Doppler US over a period of 15 years. All patients but two were Chinese war veterans seen in Taiwan about 35-55 years after their presumed infection in Mainland China. The US presentations were reviewed. The data from Doppler portal flow studies were available for 39 patients with HSJ, and compared to data from Doppler portal flow studies in 40 normal healthy volunteers and to this data in 40 patients with postnecrotic cirrhosis. A typical "coarse reticular pattern" due to fibrosis in the whole liver was noted in 40 patients (85%). Other findings included periportal fibrosis (15%), septum-like fibrous bands extending to the liver capsule (32%), and an apparent nodular liver surface (19%). Splenomegaly was noted in seven patients. While coexisting hepatocellular carcinomas (HCC) were evident in three patients, and esophageal varices were found in three others, yet both conditions were found only in patients with positive hepatitis-B-surface antigen (HBsAg). Doppler flowmetry of the portal veins in HSJ patients showed a mean flow rate of 15.34 +/- 6.82 cm/sec, and a mean flow volume of 993.21 +/- 290.63 ml/min, both showed no significant difference from those in normal adults (p > 0.5). HSJ can be confidently diagnosed in patients with hepatic fibrosis when the hepatic pathology is presented as a coarse reticular pattern. The portal hemodynamics in HSJ patients who have been isolated from the infection site (for more than 35 years) are significantly different from portal hemodynamics in cirrhotic patients and are similar to those in healthy volunteers.

Neuronal nitric oxide synthase activity is increased during granulomatous inflammation in the colon and caecum of pigs infected with Schistosoma japonicum.

Neuronal nitric oxide is a non-adrenergic non-cholinergic neurotransmitter in the enteric nervous system and plays a role in a variety of enteropathies including Crohn's and Chagas' diseases, ulcerative colitis, diabetes, atrophy and hypertrophy. The content of neuronal nitric oxide synthase (nNOS) in the colon and the caecum from pigs infected with Schistosoma japonicum was studied using immunohistochemical and histochemical staining for nNOS and nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-diaphorase), respectively. In the infected pigs, lightly, moderately and less severely inflamed tissues showed increased nNOS and NADPH-diaphorase activities in nerve cell bodies and nerve fibres in the enteric plexuses compared to control pigs. There was a significant increase in the nerve cell body density of nNOS immunoreactive nerve cell bodies in the inner submucous plexus, outer submucous plexus and in the myenteric plexus. More intensely stained nerve cell bodies and varicosities were observed in tissue from prenatally infected and prenatally infected, postnatally re-infected pigs compared to postnatally infected pigs. However, the latter showed the highest numerical density of nNOS immunoreactive nerve cell bodies. Marked increases were seen in the inner submucous plexus followed by myenteric plexus, inner circular muscle, outer submucous plexus and mucous plexus. However, in very severe inflamed tissues, the number and staining intensity of nerve cell bodies and nerve fibre varicosities were reduced in plexuses located in the lesions with the inner submucous and mucous plexuses being the most affected. There was no staining in the nervous tissue within the eosinophilic cell abscesses and productive granulomas. The apparent alterations in the activities of enzymes responsible for the generation of nitric oxide (NO) show possible alterations in the NO mediated non-adrenergic non-cholinergic reflexes in the enteric nervous tissue. These alterations might contribute to impaired intestinal motility and absorption, and other pathophysiological conditions seen during S. japonicum infections.

Studies of impact on physical fitness and working capacity of patients with advanced Schistosomiasis japonica in Susong County, Anhui Province.

To assess the impact level on physical fitness and working capacity in patients with advanced Schistosomiasis japonica, a field study was carried out. According to the records of patients with advanced schistosomiasis in Susong County, Anhui Province, 48 advanced cases without other serious chronic diseases from endemic areas in two townships and 56 healthy individuals from non-endemic area, served as control group with matched ages between 40 and 70 years and matched sex were investigated with questionnaire, anthropometric measure and hemoglobin level. The impairment level of the liver was measured by ultrasonography and physical fitness was measured by the Step test in the case and control groups. All situations including lifestyle, working, socio-economic status and residing environment was similar in the case and control groups. Average height and weight was significantly lower in the case group than in the control group (height = 156.29 and 159.41 cm; weight = 50.72 and 53.92 kg; respectively, all P < 0.05). Thirteen individuals (28.3%) in the case group had moderate reduction of working capacity or even unable to work, but only seven (12.7%) individuals in the control group had moderate reduction of working capacity and all in the control group were able to work (P < 0.01). In the past 1 year, the average working days lost was 4.11 days in the case group and 0.86 day in the control group (P < 0.01). Both groups differed significantly in symptoms of abdominal pain, diarrhea and weakness (all P < 0.05). Twenty-one cases (43.8%) had grade II impairment of the liver and eight cases (16.7%) had grade III impairment of the liver in the case group, whereas seven individuals (12.7%) had grade II impairment of the liver in the control group (P < 0.01), as assessed by ultrasound. The hemoglobin levels and the power of gripping in the case group were significantly lower than those in the control group (Hb = 111.06 and 122.27 g/l; grip = 303.83 and 344.20 N, respectively, all P < 0.01). Physical fitness scores showed the control group (score: 71.84) was significantly fitter than the case group (score: 61.09, P < 0.01). Compared with the control group, the physical fitness of the case group reduced by 15%. The results showed that physical fitness and working capacity were reduced in advanced cases. Although most of the cases were treated and had reached a status of 'clinical cure', the impact on physical fitness and working capacity still existed.

[Effect of experimental infection with Schistosoma japonicum on the pregnancy of mice].

OBJECTIVE: To understand the effect of Schistosoma infection on the gestation in mice. METHODS: Female mice infected with Schistosoma japonicum cercariae, and mated with male mice (uninfected) at 40 d and 100 d post-infection, the changes during pregnant period and the growth of offspring were observed until birth. The serum level of estradiol and progesterone of the infected mice was measured by RIA at oestrus. RESULTS: The level of estradiol and progesterone, and the pregnant rate were much lower in schistosome infected group than that of the control. The rate of abortion, the mortality of pregnant mice and the death rate due to abortion of infected mice increased significantly. The mortality increased with the time of merging male and female mice in one cage prolonged. The body weight and length of the offspring in both infected and control groups were found no significant difference. CONCLUSION: The results revealed that schistosome infection may suppress estradiol and progesterone secretion, decrease the rate of pregnancy, and that it may also increase the complications and mortality during the gestation periods.