[Biological Effect of Microplastics with Different Functional Groups on the Bacterial Communities and Metabolic Functions of Zebrafish (Danio rerio) Embryos].

To investigate the influences of functional groups on the biological effects caused by microplastics, the accumulation of three polystyrene microplastics (PS, PS-NH2, and PS-COOH) in zebrafish (Danio rerio) embryos were analyzed, and then the responses of metabolic functions and microbial communities in zebrafish larvae were revealed using the combination of the microbiome and metabolome methods. The results showed that all microplastics could accumulate in zebrafish with concentrations ranging from 143 to 175 µg·g-1, and there were no significant differences in the accumulation potentials among different PS treatments. Exposure to plain PS significantly affected the metabolic capacity of aminoglycosides in zebrafish larvae, whereas the metabolic processes of amino acids were affected by PS-NH2. In the PS-COOH treatment, the metabolic pathways of the tricarboxylic acid cycle, amino acids, and glycolysis in zebrafish were markedly altered. The metabolic functions of zebrafish larvae were changed by all PS microplastics, resulting in toxic effects on zebrafish, and the functional group modification of microplastics may have further enhanced these toxicities. Compared to that in the control, exposure to PS-NH2 significantly reduced the diversity of microbial communities in zebrafish larvae and increased the proportion of Proteobacteria in the composition, leading to an imbalance of the bacterial community in zebrafish and thus disrupting the metabolic functions in the fish. Therefore, the functional modifications of microplastics may significantly alter the related stresses on aquatic organisms, leading to unpredictable ecological risks.

[Coagulation Properties for Whole Blood Stored at 4℃].

OBJECTIVE: To study the coagulation properties the refrigerated whole blood stored at 4℃. METHODS: Ten units of whole blood were obtained from healthy volunteer donors and stored at 4±2℃ for 21 days. Samples were collected on the day after donation and on days 2, 4, 6, 8, 10, 14 and 21 for delection including complete blood count, electrolyte, APTT, PT, Fg, blood coagulation factors, and thromboelastography(TEG). RESULTS: The levels of Hb, WBC, Plt, sodium and potassium in each sample accorded with standard of storing whole blood. The level of Hb, WBC, Plt and Na+ decreased along with prolonging of storage time, while the K+ level increased along with prolonging of stored time, APTT and PT prolonged along with prolonging of thored time, PT>17 min at d 21, the Fg level change was no-obvious, The level of factor Ⅴ and Ⅷ decreased more than 50 % of baseline on d 6 and 4 respectively; the levels of factor Ⅱ, Ⅶ, Ⅸ, Ⅹ, Ⅺ, Ⅻ showed decreasing trend, but their levels were less than 40 % of baseline values at d 21. TEG test showed that no abnormalily of R value was found, the abnormal valnes of K and Angle were observed at d 21, the abnormal value of MA was observed at d 14. CONCLUSION: The whole blood stored for 10 days possesses normal coagulation function showing important significance for treatment of hemorrhage from war injury and surgical openation of heart and chest.

A case of dispermic chimerism with normal phenotype identified during ABO blood grouping.

BACKGROUND: Human chimerism with normal phenotype derived from the fusion of two different zygotes is a rare phenomenon. We describe a case of a phenotypically normal 17-year-old diagnosed with dispermic chimerism during routine ABO blood grouping. METHODS: ABO grouping, ABO genotyping, karyotyping, human leukocyte antigen (HLA) typing, and short tandem repeat (STR) analysis were performed. RESULTS: Forward typing with anti-A and anti-B sera resulted in mixed-field agglutination of red blood cells. The mother and father were blood group O and AB, respectively. The proposita had O1, A201 and B alleles in the ABO locus; O1 was a maternal allele, while A201 and B were the paternal alleles. The proposita karyotype was 46,XX/46,XY. HLA typing revealed that the proposita had three alleles (46, 51, 54) at the HLA-B locus, with the additional allele of paternal origin. STR analysis identified three alleles for five of the 15 markers (D2S1338, TPOX, D8S1179, D19S433, and D21S11) analyzed in the proposita's blood- and skin fibroblast-derived DNA. The additional alleles of TPOX, D8S1179, and D21S11 were of paternal origin. CONCLUSIONS: The genetic findings suggest that this proposita was produced by dispermic fertilization of two identical haploid ova formed by parthenogenetic activation.

[Coix lachryma jobi L varma-yuan induces apoptosis of jurkat cell line in acute T lymphoblast leukemia and its mechanism].

The aim of the present study was to investigate the anti-proliferation and pro-apoptosis effect of Coix lachrymajobi L varma-yuan on acute T lymphoblast leukemia cell line Jurkat cells and its mechanism. Jurkat cells were treated with Coix lachrymajobi L varma-yuan of various concentrations (0, 0.4, 0.8, 1.6 mg/ml) for 24h. The inhibitory ratio was measured by Cell Counting Kit-8. The effects of Coix lachrymajobi L varma-yuan on apoptosis of Jurkat cells were determined by Hoechst 33258, PI and Annexin V-FITC/PI double staining. The mitochondrial membrane potential was analyzed by JC-1 staining. The results demonstrated that Coix lachrymajobi L varma-yuan inhibited the proliferation of Jurkat cells, and induced chromatin condensation and fragmentation (characteristic of apoptosis) and loss of mitochondrial membrane potential. In conclusion, Coix lachrymajobi L varma-yuan can inhibit the cell proliferation and induce the apoptosis of Jurkat cells. These effects relate to loss of mitochondrial membrane potential. These results suggest that Coix lachrymajobi L varma-yuan may be of value in treating lymphoma.

[Effect of highway transportation on the quality of red blood cells].

This study was purposed to investigate the effect of highway transportation on the quality of blood components so as to provide experimental basis to meet the needs of military operations. The transport condition was simulated by random vibration test. The red blood cells, leukocyte-reduced red blood cells, washed red blood cells were randomly vibrated (C Road) for 4 hours. Then, these blood components were stored in refrigerator for 15 days (4 degrees C). Six milliliters of blood were collected before vibration, after vibration, and at day 15 days of storage after vibration, respectively. The suspension was isolated. The free hemoglobin (FHb), routine hematological parameters, and biochemical indexes were determined. The results showed that FHb, lactate dehydrogenase (LDH), K(+) of red blood cells and leukocyte-reduced red blood cells did not significantly change after vibration and storage. However, FHb, LDH and K(+) of washed red blood cells increased significantly after simulated transportation (p < 0.05). The levels of these parameters at day 15 of storage after vibration were also significantly higher than those after vibration (p < 0.01). The changes of other hematological parameters were not significant in three blood components after vibration (C Road) and storage for 15 day. In conclusion, red blood cells and leukocyte-reduced red blood cells were qualified for clinic transfusion even after transportation within 4 hours for 15 day storage later, if they were kept in proper blood container and protected from damping. However, the washed red blood cells could not be used for clinic after similar transport in the military operations.

[Effects of triptolide on proliferation and apoptosis of Jurkat cell line in acute T lymphocytic leukemia].

The aim of this study was to investigate the anti-proliferation and pro-apoptosis of triptolide on Jurkat cell line in acute T lymphocytic leukemia. The Jurkat cells were treated with various concentrations of triptolide (0, 1, 2, 4, 8, 16 microg/L) for 12 hours. The inhibitory ratio was measured by Cell Counting Kit-8 assay. The effects of triptolide on apoptosis of Jurkat cells were determined by DNA fragmentation (DNA ladder), Hoechst 33258, PI and Annexin V-FITC/PI double staining. The results demonstrated that triptolide inhibited the proliferation of Jurket cells. The 50% inhibitory concentration (IC(50)) was 4.0 microg/L. Chromatin condensation in the cells treated with triptolide could be seen by light microscopy. DNA electrophoresis showed evidence of nuclear fragmentation (DNA ladder). The hypoploid (sub-G(1)) population was increased after treatment with triptolide. The translocation of phosphatidylserine at the outer surface of the cell plasma membrane could be induced by triptolide. After treatment with triptolide for 12 hours, the rates of apoptotic cells were significantly increased. Moreover, these pro-apoptosis effects were in time-dependent manner. It is concluded that triptolide can inhibit the proliferation and induce the apoptosis of Jurkat cells. This study provides experimental basis for clinical use of triptolide in leukemia therapy.

Molecular prenatal diagnosis in 2 pregnancies at risk for spondyloepiphyseal dysplasia congenita.

BACKGROUND: Spondyloepiphyseal dysplasia congenita (SEDC) is an autosomal dominant skeletal dysplasia characterized by short stature, abnormal epiphyses, and flattened vertebral bodies. Secondary prevention of SEDC can be achieved by prenatal diagnosis. Reports of antenatally-diagnosed SEDC fetuses have been very rare and molecular prenatal diagnosis even rarer. We previously reported a familial G504S mutation in the type II collagen (COL2A1) gene resulting in SEDC. In this study, molecular prenatal diagnosis was performed to 2 couples in this family with pregnancies at risk for SEDC. METHODS: Amniotic fluid was sampled by amniocentesis under ultrasound guidance at 19+3 and 18+6 weeks' gestation, respectively. Karyotype and molecular genetic analysis were performed on cultured amniotic fluid cells. Maternal cell contamination was excluded by short tandem repeat (STR) analysis. Direct DNA sequencing and DHPLC were conducted to detect the potential mutation in exon 23 of COL2A1 gene. Both women underwent serial sonograms because they insisted that the molecular diagnosis should be confirmed by another method, although they had been informed that mutation analysis is predictive of the disease. RESULTS: Karyotype of both fetuses was normal and molecular genetic analysis revealed that fetus 1 carried a G504S mutation in exon 23, while fetus 2 was normal. In case 1, femur length of the fetus was markedly below the 5th centile at 23 weeks' gestation, which confirms the accuracy of molecular diagnosis. A medical termination was carried out at 27+5 weeks' gestation and a male fetus with a relatively large head and short limbs was delivered. The fetal radiograph demonstrated a number of features, including generalised platyspondyly, absent ossification of the vertebral bodies in the cervical region and significant shortening of the long bones. The diagnosis of SEDC was thus confirmed clinically. Ultrasound monitoring of fetus 2 showed that its femur length was normal for gestational age at repeated scans, which was consistent with the molecular diagnosis. CONCLUSIONS: Molecular analysis allows early and accurate prenatal diagnosis for SEDC once mutation is known in a family. However, considering the poor genotype/phenotype correlation in many cases of SEDC, the combination of ultrasound as well as molecular genetic approach might be needed.

Induction of apoptosis by recombinant soluble human TRAIL in Jurkat cells.

OBJECTIVE: To investigate the therapeutic potential of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF superfamily, and to analyze TRAIL-induced apoptosis in Jurkat cells. METHODS: Expression of TRAIL receptors (DR4 and DR5) was detected by reverse transcriptase-polymerase chain reaction (RT-PCR). Cytotoxic effects were determined by colony formation assay and a cell counting kit. The effects of recombinant TRAIL on apoptosis of Jurkat cells were determined by DNA fragmentation (DNA ladder) and PI staining. Changes in mitochondrial membrane potential were detected with JC-1 fluorescence. RESULTS: TRAIL inhibited the proliferation and induced internucleosomal DNA fragmentation (characteristic of apoptosis) and loss of mitochondrial membrane potential. CONCLUSION: Recombinant soluble TRAIL can be used as a therapy for cancer.

[Study on fetal SRY gene in maternal plasma using nested polymerase chain reaction].

OBJECTIVE: To develop a nested polymerase chain reaction (PCR) technique for fetal SRY gene identification using cell-free fetal DNA in maternal plasma. METHODS: Peripheral blood samples were obtained from 30 pregnant women and cell-free DNA was extracted by the phenol/chloroform method from plasma. The nested PCR was carried out to amplify the fragment of SRY gene by two sets of PCR primer pairs. Direct sequencing analysis was then performed on the PCR product. RESULTS: Among the 17 women bearing male fetuses, SRY sequences were detected in 15 plasma samples after nested PCR amplification, while none of the 13 women bearing female fetuses had the positive results. The accuracy and sensitivity were 93.3% (28/30) and 88.2% (15/17), respectively. CONCLUSION: The phenol/chloroform extraction for fetal DNA in maternal plasma was effective and simple. And the nested PCR amplification of SRY sequence is a convenient and low-cost approach for the non-invasive early prenatal diagnosis of sex-linked inheritant diseases.

[Scientific consideration and topic selection in the field of andrology].

The improvement of diagnosis and treatment of andrological disease depends on scientific advances in the corresponding domain of andrology. In this article, the author thought topic selection was of great significance for the improvement of diagnosis and treatment based on his clinical and scientific experience for years in the field of andrology. Topic selection should be closely combined with clinical practice and follow the principles of importance, innovation, feasibility and reality, which meets the demands of basic, therapeutic and epidemiologic aspects in andrology research. Several common approaches to topic selection were discussed as well in the article.

[Cloning, expression and purification of human TNF-related apoptosis-inducing ligand in Escherichia coli].

OBJECTIVE: To clone human tumor necrosis factor-related apoptosis-inducing ligand (TRAIL, 114-281) cDNA and develop an inducible system for expression in E. coli. METHODS: The human TRAIL (114-281) cDNA was amplified with the total RNA from the human peripheral blood monocytes by RT-PCR. The cDNA was inserted into pMD T vector. The selected integrants were confirmed by PCR screen, digestion with restriction enzymes and DNA sequencing. Then, the insert of human TRAIL cDNA was subcloned into prokaryotic expression vector pET28a. The construction of prokaryotic expression vector was proofed correct by RT-PCR and digestive identification. The recombinant protein was induced by IPTG (isopropyl-beta-D-thiogalactopyranoside) . The sTRAIL inclusion bodies were refolded by dilution method. Refolded protein was purified with column chromatography. RESULTS: Agarose gel electrophoresis of product of RT-PCR revealed a band around 500bp, which was expected. The positive integrants were confirmed by PCR screen and digestion with restriction enzymes. The same band as RT-PCR product was showed by PCR screen and digestion with restriction enzymes. Then the selected integrants were confirmed by DNA sequencing. The sequence was checked in GenBank. The construction of prokaryotic expression vector pET 28a was proofed correct by RT-PCR and digestive identification. TRAIL protein was successfully induced by IPTG in E. coli BL21. The results also showed that the protein was expressed as inclusion bodies. After the sTRAIL inclusion bodies were solubilized and refolded, the protein expressed was purified with one band, which was about 20kD, analyzed by SDS-PAGE. CONCLUSION: These results suggested that the hsTRAIL was cloned, expressed and purified in the present study. Significant quantities of TRAIL produced by this method should allow further studies in determining the physiological significance and function of TRAIL in the future.

[Total antioxidant capacity of seminal plasma in fertile and infertile men].

OBJECTIVE: To evaluate total antioxidant capacity (TAC) of seminal plasma in fertile and infertile men and understand the relation between seminal plasma TAC and male fertility. METHODS: Two hundred and twenty-five infertile men were divided into 10 cases of obstructive azoospermic men, 42 cases of non-obstructive azoospermic men,20 cases of oligozoospermic men, 78 cases of asthenozoospermic men, 57 cases of oligoasthenozoospermic men, and 18 cases of normozoospermic men, then 28 fertile men were taken as the control. The seminal parameter analysis was performed by computer-assisted semen analysis (CASA) system. Seminal plasma TAC was measured using spectroscopic analysis. RESULTS: Seminal plasma TAC were (1.71 +/- 1.33) U in obstructive azoospermic men, (12.73 +/- 9.44) U in non-obstructive azoospermic men, (10.85 +/- 6.64) U in oligozoospermic men, (13.88 +/- 8.24) U in asthenozoospermic men, (11.20 +/- 7.02) U in oligoasthenozoospermic men, (18.07 +/- 8.73) U in normozoospermic men, and (19.82 +/- 6.33) U in fertile men. There was no significant difference in TAC between normozoospermic men and fertile men (P > 0.05). Compared with fertile men, seminal plasma TAC in other infertile groups was significantly lower (P < 0.01). There were significantly made positive correlation between seminal plasma TAC and sperm density (r = 0.182, P < 0.05), as well as sperm with grade a (r = 0.150, P < 0.05). CONCLUSION: Seminal plasma TAC is closely related to male fertility, and the decreased level of TAC in seminal plasma may be one of the causes of male infertility.

[Recent advances in proPSA on early detection in prostate cancer].

The precursor of prostate specific antigen (proPSA) are distinct molecular forms of free PSA in serum. proPSA is comprised of native proPSA as well as several truncated forms, in which [-2] proPSA and [-4] proPSA are more prostate cancer (PCa)-associated than [-7] proPSA and [-5] proPSA. Clinical studies have recently provided evidence that [-2] proPSA can significantly improve the detection of PCa, particularly in patients with total serum PSA values less than 4 microg/L. In this paper, the mechanism and characteristics of proPSA formation and impact of proPSA on the early detection of PCa are reviewed.

[Examination and significance of semenial prostate specific antigen in infertile patients].

OBJECTIVE: To investigate the significance of prostate specific antigen (PSA) examination in seminal plasma of infertile patients. METHODS: Eighty-five infertile patients were collected randomly. The level of PSA in seminal plasma was detected by ELISA method. The correlations between PSA and several seminal parameters including sperm density, motility and acid phosphatase (ACP) were analyzed. RESULTS: The PSA, ACP concentrations and sperm motility in 65 cases of abnormal liquefaction patients were obviously lower than those in normal liquefaction patients(P < 0.01). But there were no significant differences in sperm density among the three groups(P > 0.05). PSA levels were significantly correlated with ACP and sperm motility(P < 0.01). CONCLUSIONS: The seminal PSA in infertile patients is markedly correlated with semen liquefaction. The abnormal quality and quantity of PSA can result in a depression of sperm motility and subinfertility.

[Advances in microinsemination with spermatid].

Men with non-obstructive azoospermia(NOA) can now be treated by using intra-oocyte round spermatid injection(ROSI) or elongated spermatid injection(ELSI). Spermatids can be retrieved from semen or from testis biopsy specimens. But the rates of fertilization and pregnancy with spermatids have been disappointing. Many problems limiting success rate and hindering a wide application of this technique still remain unresolved, including the incomplete maturation of spermatid nuclear, oocyte activation and identification of a live spermatid.

[Inhibin B levels of serum and seminal plasma in fertile and infertile males].

OBJECTIVES: To investigate the possible differences in the inhibin B levels of seminal plasma and serum between fertile and infertile males and to obtain information on the relation between serum inhibin B or seminal plasma inhibin B and spermatogenesis. METHODS: Semen and blood samples were collected from fertile(n = 20), oligospermia(n = 20), asthenospermia(n = 22) and non-obstructive azoospermia(NOA) (n = 20) males at 8:00 am = 10:00 am. Semen parameters were analyzed. Levels of inhibin B in seminal plasma and serum, ACP, Fru, alpha-Glu in seminal plasma, serum levels of FSH, T, LH were determined. RESULTS: Both levels of serum inhibin B and levels of seminal plasma inhibin B correlated significantly negatively with serum FSH(r = -0.536, P < 0.001 vs r = -0.288, P = 0.01), and statistically positively with sperm concentration(r = 0.49, P < 0.001 vs r = 0.48, P < 0.001). There was positive correlation between levels of seminal plasma inhibin B and activity of alpha-Glu in seminal plasma (r = 0.377, P = 0.001). The difference in levels of seminal plasma inhibin B was found only between fertile males or asthenospermia and NOA (P < 0.01 and P < 0.05, respectively). However, significant differences in levels of serum inhibin B were found not only between males with normal sperm concentration (including fertile males and asthenospermia) and NOA (P < 0.01), fertile males and oligospermia (P < 0.05), but also between oligospermia and NOA (P < 0.05). There was no correlation between serum inhibin B and seminal plasma inhibin B. CONCLUSIONS: Both levels of serum inhibin B and seminal plasma inhibin B could reflect testis spermatogenesis status. Levels of seminal plasma inhibin B could also reflect the function of seminiferous duct, but the wide range of values limited its applicability.

[Detection of cholesterol ester transfer protein in semen of infertile patients].

OBJECTIVES: To detect the cholesterol ester transfer protein (CETP) levels in semen of infertile patients and evaluate the correlation between CETP in semial plasma and infertility. METHODS: One hundred and sixty-three infertile patients and fifteen fertile males were selected randomly. The routine examination of ejaculates was fulfilled by computer aided semen analysis (CASA). The CETP levels in all seminal plasma samples and fifty-five serum samples were detected by ELISA method. RESULTS: The CETP levels in infertile patients and fertile males were (2.21 +/- 1.23) microgram/L and (1.40 +/- 0.45) microgram/L, respectively. There were no significant differences between the two groups(P > 0.05). And there were no significant differences of CETP levels in seminal plasma among groups of azoospermia(n = 29), oligoasthenozoospermia (n = 58), oligospermia(n = 15), asthenozoospermia(n = 44) and normozoospermia(n = 17) in the infertile patients(P > 0.05). The CETP in seminal plasma and serum were detected in 55 infertile patients, and there was no correlation between CETP levels in seminal plasma and serum using Spearman analysis(r = 0.009, P > 0.05). The mean CETP level in seminal plasma was almost 1/1,000 of that in serum. CONCLUSIONS: The CETP level in seminal plasma is extremely low and has no relation with the changes of sperm density or motility. It may ensure the integrity of sperm membrane before the sperm enters into female genital tract.

[Detection of IgG and IgM antibodies against Chlamydia trachomatis in semen of asymptomatic infertile patients].

OBJECTIVES: To evaluate the clinical significance of the detection of IgG and IgM antibodies against Chlamydia trachomatis (CT) in semen of asymptomatic infertile patients. METHODS: One hundred and sixteen asymptomatic infertile patients and eighteen fertile males were selected randomly. The routine parameter analysis of semen was fulfilled by computer aided semen analysis(CASA). Then the seminal plasma was separated and the IgG, IgM antibodies against CT in seminal plasma were determined with ELISA method. RESULTS: IgG and IgM antibodies against CT were present in 13.8% (16/116) and 3.4% (4/116) of the semen of infertile patients, while for the fertile males the percentages were 11.1% (2/18) and 0, respectively. There were no differences between the two groups(P > 0.05). In the infertile patients, 22 patients were azoospermia. And in the rest 94 infertile patients, the percentages of IgG and IgM antibodies in abnormal sperm density group were 21.4% (6/28) and 7.1% (2/28), which were higher than those in normal group, but there were no statistical differences(P > 0.05). Similarly, the IgG, IgM antibodies were not correlated with the sperm motility(P > 0.05). The positive percentage of CT in 116 patients was 25.9% (30/116). CONCLUSIONS: The percentages of IgG and IgM antibodies against CT in semen of asymptomatic infertile patients are similar to that in fertile males, which do not correlate with the changes of semen parameters, and may not be used for indication of CT infection.

[Isolation and identification of spermatids from mouse testis].

OBJECTIVES: To develop a simple and effective method by which spermatids can be isolated from mouse testis. METHODS: Combination of enzymatic digestion was used to prepare suspension of spermatogenic cells from adult mouse testis, and then a modified discontinuous Percoll gradient (15%, 22%, 30%, 40%, 50%, 60%) centrifugation method was introduced to isolate spermatids from the cellular suspension. The content of spermatids in each isolated fraction by Percoll method was determined by morphology (Wright-Giemsa staining) and flow cytometry analysis, and the viability of spermatogenic cells was assessed using Eosin Y exclusion test. RESULTS: More than 97% of the testicular cells remained their viability after enzymatic digestion. After Percoll centrifuged, six fractions were formed. In each isolated fraction, the 22% fraction contained mostly spermatids(mean 86.7%) and cell viability was more than 85.5%. While in the 30% fraction, immature spermatogenic cells were present, and more than 92% of the cells remained their viability. CONCLUSIONS: A large of relatively purified spermatids can be isolated from mouse testis by enzymatic digestion combined discontinuous Percoll gradient centrifugation method.

Autosomal aberrations associated with testicular dysgenesis or spermatogenic arrest in Chinese patients.

AIM: To analyze the relationship between autosomal aberrations and testicular dysgenesis or spermatogenic arrest in Chinese patients and to map the corresponding regions on each autosome in regard to the recorded aberrations accompanying these distubances. METHODS: One hundred and nineteen cases of aberrant karyotypes with testicular dysgenesis, azoospermia or oligozoospermia reported in five Chinese journals and one monograph were analyzed. For each autosome, the type and frequency of chromosomal aberrations were counted and the regions corresponding to the disturbances were mapped out. RESULTS: Chromosomes 13, 14, 9, 21 exhibited a high frequency of aberration and bands 14q11 and 13p11 were the two regions showing the highest linkage to testicular dysgenesis or infertility. The frequency of chromosomal aberrations was higher in bands 9p11 and 22q than in others. CONCLUSION: Autosomes 13, 14, 9 and 21 in the order of importance play a critical role in testicular development and spermatogenesis and other autosomes may also contribute; the following regions, 14q11, 13p11,9p11, and 22q, are of high significance.