PURPOSE: Henoch-Schönlein purpura (HSP) is diagnosed based on characteristic skin changes. This study aimed to identify the serum biomarkers of HSP in children. EXPERIMENTAL DESIGN: We performed proteomic analysis of serum samples from 38 paired pre- and posttherapy HSP patients and 22 healthy controls using a combination of magnetic bead-based weak cation exchange and MALDI-TOF MS. ClinProTools was used to screen the differential peaks. Then, LC-ESI-MS/MS was performed to identify the proteins. ELISA was used to verify the expression of whole protein in the serum of 92 HSP patients, 14 peptic ulcer disease (PUD) patients and 38 healthy controls, which were prospectively collected. Finally, logistic regression analysis was performed to analyze the diagnostic value of the above predictors and existing clinical indicators. RESULTS: Seven potential HSP serum biomarker peaks (m/z:1228.95, m/z:1781.22, m/z:1468.43, m/z:1619.53, m/z:1868.41, m/z:1694.05, m/z:1743.25) with higher expression in the pretherapy group and one peak (m/z:1947.41) with lower expression in the pretherapy group were all identified as peptide regions of albumin (ALB), complement C4-A precursor (C4A), tubulin beta chain (TUBB), isoform 1 of fibrinogen alpha chain (FGA), and ezrin (EZR). The expression of identified proteins was validated by ELISA. Multivariate logistic regression analysis showed that serum C4A EZR and ALB were independent risk factors for HSP, serum C4A and lgA were independent risk factors for HSPN, and serum D-dimer was an independent risk factor for abdominal HSP. CONCLUSIONS AND CLINICAL RELEVANCE: These findings revealed the specific etiology of HSP from the perspective of serum proteomics. The identified proteins might serve as potential biomarkers for HSP and HSPN diagnoses. SIGNIFICANCE: Henoch-Schönlein purpura (HSP) is the most common systemic vasculitis in children, and its diagnosis depends primarily on characteristic skin changes. Early diagnosis of non-rash patients is difficult, especially for abdominal and renal types (Henoch-Schönlein purpura nephritis, HSPN). HSPN has poor outcomes, is diagnosed based on urinary protein and/or haematuria, and cannot be detected early in HSP. Patients with an earlier diagnosis of HSPN appear to have better renal outcomes. Our plasma proteomic analysis of HSP in children revealed that HSP patients could be distinguished from healthy controls and peptic ulcer disease patients using complement C4-A precursor (C4A), ezrin, and albumin. C4A and IgA could distinguish HSPN from HSP in the early stages, and D-dimer was a sensitive index used to distinguish abdominal HSP; identifying these biomarkers could promote the early diagnosis of HSP, especially pediatric HSPN and abdominal HSP, thereby improving precision therapy.

PARP inhibitors are a potential class of chemotherapeutic drugs but PARP inhibitor response has not been explored systematically. We lack a specific understanding of the subset of the proteome preferentially modified in various cancers by PARP inhibitors. Implications of PARP inhibitor and PARP1 in cervical cancer treatment and resistance are not fully elucidated. We conducted a mass spectrometry-based proteomic analysis of cervical cancer Hela cells treated with olaparib. We aimed to identify the alteration in the protein signaling pathway induced by PARP inhibitors beyond the DNA damage response pathway. Our data demonstrate a significant reduction in PARP activity and enhanced cell death after olaparib treatment. We further observed articulated proteomic changes with a significant enrichment of proteins in diverse cellular processes. The differentially expressed proteins were predominantly associated with RNA metabolism, mRNA splicing, processing, and RNA binding. Our data also identified proteins that could probably contribute to survival mechanisms resulting in resistance to PARP inhibitors. Hence, we put forth the overview of proteomic changes induced by PARP inhibitor olaparib in cervical cancer cells. This study highlights the significant proteins modified during PARP inhibition and thus could be a probable target for combination therapies with PARP inhibitors in cervical cancer. SIGNIFICANCE.

Cytoplasmic male sterility (CMS) is critical in maximizing crop yield and quality by utilizing tobacco heterosis. However, the mechanism of tobacco CMS formation remains unknown. Using paraffin section observation, transcriptome sequencing, and TMT proteomic analysis, this study describes the differences in expression profiles in morphology, transcription, and translation between the sua-CMS tobacco line (MSYY87) and its corresponding maintainer line (YY87). According to the microspore morphology, MSYY87 began to exhibit abnormal microspore development during the early stages of germination and differentiation (androgynous primordium differentiation stage). According to transcriptomic and proteomic analyses, 17 genes/proteins involved in lipid transport/binding and phenylpropane metabolism were significantly down-regulated at both the mRNA and protein levels. Through further analysis, we identified some key genes that may be involved in tobacco male sterility, including β-GLU related to energy metabolism, 4CL and bHLHs related to anther wall formation, nsLTPs related to pollen germination and anther cuticle, and bHLHs related to pollen tapetum degradation. We speculate that the down-regulation of these genes affects the normal physiological metabolism, making tobacco plants show male sterility. SIGNIFICANCE: Cytoplasmic male sterility (CMS) plays a vital role in utilizing tobacco heterosis and enhancing crop yield and quality. We observed paraffin sections and conducted transcriptome sequencing and mitochondrial proteomics to examine the tobacco CMS line Yunyan 87 (MSYY87) and its maintainer line Yunyan 87 (YY87). The down-regulation expression of β-GLU resulted in insufficient ATP supply, which resulted in disordered energy metabolism. The down-regulation expression of 4CL, nsLTPs and bHLHs may affect the formation of anther wall and anther cuticle, pollen germination, as well as the degradation of pollen tapetum. These various abnormal physiological processes, the male sterility of tobacco is finally caused. The findings shed light on the molecular mechanisms of tobacco CMS and serve as a model for fertility research in other flowering plants.

The identification of tumor related membrane protein is important for both cancer diagnosis and targeted therapy. Currently, the number of ideal clinical biomarkers is still limited partially because of lacking efficient methods in biomarker discovery. Targeting peptides are generated by library screening and can recognize their cognate targets with high specificity and affinity. In addition, these functional peptides have been considered to be a valuable molecule for both imaging detection and targeting therapy in oncology. The selected peptides can be used to identify cell-surface protein biomarkers of cancer cells. In our study, the peptide (VECYLIRDNLCIY) derived from the bacteria displaying library worked as a bait to capture its binding partner and aldolase A was identified as the candidate. The results indicated that aldolase A' expression level on the cell membrane was regulated by PI3K and aldolase A located on the membrane could inhibit the aggression of tumors through mediating cell metabolic pathway. Aldolase A could work as the joint for the metabolic and signal pathways related to tumor progression. In our work, we demonstrated a promising technology for selecting and identifying binding partners for cell-specific peptides that enables discovery of new tumor biomarkers, showing great scientific study values and clinical translation potencies. SIGNIFICANCE: MS-based cancer biomarker discovery provides promising target candidates for cancer diagnosis and therapy. However, the inevitable limits make it inconvenient in the process of sample preparation and data analysis. In this way, the small molecular probes show some advantages due to their readily availability and specific binding affinity such as the aptamers screened with SELEX technology and peptides derived from displaying libraries. In the present study, aldolase A was proved to be the membrane binding partner of a specific peptidic ligand towards ZR-75-1 tumor cell. It was discovered that membrane aldolase A was more sensitive and observable than other subcellular fractions in response to cellular metabolic state alteration or glucose availability. In addition, the reduced membrane-localized aldolase A expression indicated a more aggressive tumor phenotype and was accompanied by the upregulation of MMP-2/MMP-9. The non-glycolysis activity endowed it with potential utility as a tumor diagnostic marker and therapeutic target. This work demonstrates the practicability of screened peptide in cancer biomarker discovery, facilitating the development of diagnostic tools and therapeutic approaches to cancer, and markedly improves our understanding of cancer biology.

CVST is a type of venous stroke that mainly affects young adults with no reliable diagnostic markers and effective treatment strategies for secondary pathologies. However, the underlying pathological molecular mechanisms remain unclear. Here, we systematically analyzed the molecule profiling of the cerebrospinal fluid (CSF) in CVST patients via tandem mass tag (TMT)-based proteomics for the first time, aiming to reveal the pathogenesis and provide evidence for the diagnosis and treatment of CVST. Five CVST patients and five control patients were selected, and CSF samples were analyzed by TMT proteomics. Differentially expressed proteins (DEPs) were acquired and bioinformatics analysis was performed. Besides, parallel reaction monitoring (PRM) was utilized to validate the DEPs. 468 differentially expressed proteins were screened, 185 of which were up-regulated and 283 were down-regulated (fold change >1.2, P < 0.05). Bioinformatics analysis displayed that these proteins were significantly enriched in multiple pathways related to a variety of pathophysiological processes. PRM verification showed that apolipoprotein E, MMP-2, neuroserpin, clusterin, and several other molecules were down-regulated. These identified proteins reveal unique pathophysiological characteristics secondary to CVST. Further characterization of these proteins in future research could enable their application as potential therapeutic targets and biomarkers in CVST therapy. SIGNIFICANCE: Cerebral venous sinus thrombosis (CVST) is an underrated and potentially fatal cause of stroke with a reported mortality of 5-10% worldwide. Currently, in addition to anticoagulant and thrombolytic therapy, effective treatments targeting the injured brain parenchyma after CVST remain limited. Besides, accurate diagnostic markers are still sorely lacking. In the present study, we will detect the alterations of the CSF protein spectrum of CVST patients by TMT technique, screen differentially expressed proteins, analyze the functions of these signals through bioinformatics methods, and finally validate the key molecules through parallel reaction monitoring (PRM) technique. Collectively, the study aimed to offer a reference for the discovery of specific protein/pathway alterations in the CSF of CVST patients and further reveal the underlying pathogenesis, thereby providing evidence for the diagnosis and treatment of CVST.

Histone deacetylase 1 (HDAC1) plays a key role in diverse cellular processes. With the aberrant expression of HDAC1 linked to many diseases, including cancers, HDAC inhibitors have been used successfully as therapeutics. HDAC1 has been predominantly associated with histone deacetylation and gene expression. Recently, non-histone substrates have revealed diverse roles of HDAC1 beyond epigenetics. To augment discovery of non-histone substrates, we introduced "substrate trapping" to enrich HDAC1 substrates using an inactive mutant. Herein, we performed a series of proteomics studies to test the robustness of HDAC1 substrate trapping. Based on our recent results documenting that different HDAC1 mutants preferentially bound different substrates, which suggested that multiple mutants could be used for efficient trapping, trapping with three single point mutants simultaneously identified several potential substrates uniquely compared to a single mutant alone. However, a greater number of biologically interesting hits were observed using only a single mutant, which suggests that the C151A HDAC1 mutant is the optimal trap. Importantly, comparing independent trials with a single mutant performed by different experimentalists and HEK293 cell populations, trapping was robust and reproducible. Based on the reproducible trapping data, carnosine N-methyltransferase 1 (CARNMT1) was validated as an HDAC1 substrate. The data document that mutant trapping is an effective method for discovery of unanticipated HDAC substrates. SIGNIFICANCE: Histone deacetylase (HDAC) proteins are well established epigenetic transcriptional regulators that deacetylate histone substrates to control gene expression. More recently, deacetylation of non-histone substrates has linked HDAC activity to functions outside of epigenetics. Given the use of HDAC inhibitor drugs as anti-cancer therapeutics, understanding the full functions of HDAC proteins in cell biology is essential to future drug design. To discover unanticipated non-histone substrates and further characterize HDAC functions, inactive mutants have been used to "trap" putative substrates, which were identified with mass spectrometry-based proteomics analysis. Here multiple trapping studies were performed to test the robustness of using inactive mutants and proteomics for HDAC substrate discovery. The data confirm the value of trapping mutants as effective tools to discover HDAC substrates and link HDAC activity to unexpected biological functions.

Proteins and translationally modified proteins like phosphoproteins have essential regulatory roles in tumorigenesis. This study attempts to elucidate the dysregulated proteins driving colorectal cancer (CRC). To explore the differential proteins, we performed iTRAQ labeling proteomics and TMT labeling phosphoproteomics analysis of CRC tissues and adjacent non-cancerous tissues. The functions of quantified proteins were analyzed using Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and Subcellular localization analysis. Depending on the results, we identified 330 differential proteins and 82 phosphoproteins in CRC. GO and KEGG analyses demonstrated that protein changes were primarily associated with regulating biological and metabolic processes through binding to other molecules. Co-expression relationships between proteomic and phosphoproteomic analysis revealed that TMC5, SMC4, SLBP, VSIG2, and NDRG2 were significantly dysregulated differential proteins. Additionally, based on the predicted co-expression proteins, we identified that the stem-loop binding protein (SLBP) was up-regulated in CRC cells and promoted the proliferation and migration of CRC. This study reports an integrated proteomic and phosphoproteomic analysis of CRC to discern the functional impact of protein alterations and provides a candidate diagnostic biomarker or therapeutic target for CRC. SIGNIFICANCE: Combining one or more high-throughput omics technologies with bioinformatics to analyze biological samples and explore the links between biomolecules and their functions can provide more comprehensive and multi-level insights for disease mechanism research. Proteomics, phosphoproteomics, metabolomics and their combined analysis play an important role in the auxiliary diagnosis, the discovery of biomarkers and novel therapeutic targets for colorectal cancer. In this integrated proteomic and phosphoproteomic analysis, we identified proteins and phosphoproteins in colorectal cancer tissue and analyzed potential mechanisms contributing to progression in colorectal cancer. The results of this study provide a foundation to focus future experiments on the contribution of altered protein and phosphorylation patterns to prevention and treatment of colorectal cancer.

Among the scorpions found in Brazil, Tityus bahiensis is one of the species that causes most of the reported human accidents. In spite of this important constatation, the venom composition description is not available in the literature. Thus, this venom remains not properly studied, segregating this particular species into an abandoned, forgotten condition. In the present study, chromatographic separation (RP-HPLC-C18) and proteomic analyses were employed to unravel the diversity, complexity, and proportional distribution of the main peptides and proteins found in the scorpion venom. Moreover, sequence analyses and the presence of new isoforms and toxins are discussed based on a database comparison with other Tityus toxins. Our results show the presence of a wide diversity of potassium and sodium channel toxins and enzymes, such as metallopeptidases and hyaluronidases, as previously described for other species. However, the current work also describes for the first time, at the protein level, phospholipase, angiotensin-converting enzyme, cysteine-rich proteins, serine peptidase inhibitors peptides, and antimicrobial peptides. Finally, thorough data analyses allowed the description of the venom toxins distribution regarding their diversity and relative quantity. SIGNIFICANCE: The work presents the first Tityus bahiensis proteome. We have focused on describing the neurotoxin variability in terms of their isoforms/amino acid substitutions. Understanding the natural variations in the toxins' sequences is essential, once the affinity of these peptides to their respective receptors/ionic channels will vary depending on the specific peptide sequences. Moreover, the current study describes some proteins present in the venom, including enzymes being described for the first time in scorpion venoms, such as PLA2 and ACE. Moreover, we describe the individual relative quantity distribution for the different protein classes identified, as well as their variability in the T.bahiensis venom. Finally, this study also reports the development of a simple straightforward chromatographic method for scorpion venom fractionation.

Contryphans, peptides containing a single disulfide bond, are found abundantly in cone snail venom. The analysis of a large dataset of available contryphan sequences permits a classification based on the occurrence of proline residues at positions 2 and 5 within the macrocyclic 23-membered disulfide loop. Further sequence diversity is generated by variable proteolytic processing of the contryphan precursor proteins. In the majority of contryphans, presence of Pro at position 2 and a D-residue at position 3 leads to a slow conformational dynamics, manifesting as anomalous chromatographic profiles during LC analysis. LC-MS analysis of diverse contryphans suggests that elution profiles may be used as a rapid diagnostic for the presence of the Pro2-DXxx3 motif. Natural sequences from C.inscriptus and C.frigidus together with synthetic analogs permit the delineation of the features necessary for abnormal chromatographic behaviour. A diagnostic for the presence of Pro at position 5 is obtained by the observation of non-canonical fragment ions, generated by N-Cα bond cleavage at the dehydroalanine residue formed by disulfide cleavage. Anomalous LC profiles supports Pro at position 2, while non-canonical mass spectral fragments established Pro at position 5, providing a rapid method for contryphan analysis from LC-ESI-MS/MS profiles of crude Conus venom. SIGNIFICANCE: Contryphans are peptides, widely distributed in cone snail venom, which display extensive sequence diversity. Heterogeneity of proteolytic processing of contryphan precursor proteins, together with post-translational modifications contributes to contryphan diversity. Contryphans, identified by a combination of mass spectrometry and transcriptomic analysis, are classified on the basis of sequence features, primarily the number of proline residues within the disulfide loop. Conformational diversity arises in contryphans by cis-trans isomerization of Cys-Pro bonds, resulting in characteristic chromatographic profiles, permitting identification even in crude venom mixtures. Rapid identification of contryphans in cone snail peptide libraries is also facilitated by diagnostic mass spectral fragments arising by non-canonical cleavage of the N-Cα bond at Cys(7).

Fragile X mental retardation protein (FMRP) deficit resulted from mutations in its encoded fragile X mental retardation 1 (Fmr1) gene is a common inherited cause of Fragile X syndrome (FXS) characterized by intellectual disability and autism spectrum disorder (ASD). The FMRP absence-induced altered gene expression in prefrontal cortex (PFC) are associated with autistic behaviors. However, there lacks a large-scale protein profiling in the PFC upon loss of FMRP. This study used a TMT-labeled proteomic analysis to identify a protein profile of the PFC in the Fmr1 knockout mouse. A total of 5886 proteins were identified in the PFC with 100 differentially abundant proteins (DAPs) in response to FMRP deficiency. Bioinformatical analyses showed that these DAPs were mostly enriched in immune system, extracellular part and complement and coagulation cascades. The complement and coagulation cascades include 6 upregulated proteins (SERPING1, C1QA, C3, FGA, FGB and FGG), which are associated with fibrin degradation, cell lysis, degranulation chemotaxis and phagocytosis linked to activation of immune and inflammatory responses. Thus, our data provide an altered protein profile upon loss of FMRP in the PFC, and suggest that the enhancement of complement and coagulation cascades might contribute to etiological and pathogenic roles of ASD in FXS. SIGNIFICANCE: The etiology of autism spectrum disorder (ASD), a group of neurobiological disorders characterized by deficits in social interaction barriers and other abnormal behaviors, is still elusive. Autistic-like phenotypes are present in both Fragile X syndrome (FXS) patients and FMRP-deficiency FXS models. Given that prefrontal cortex is a critical brain area for social interaction, the FMRP absence induced-changes of a subset of proteins might contribute to ASD in FXS. Using a comprehensive proteomic analysis, this study provides a prefrontal protein profile of the FMRP-absent mouse with a total of 100 differentially abundant proteins (DAPs). Bioinformatic analyses suggest that these DAPs are mainly involved in the regulations of immune system and complement and coagulation cascades. We also show that 6 upregulated proteins (SERPING1, C1QA, C3, FGA, FGB and FGG) in the complement and coagulation cascades are associated with fibrin degradation, cell lysis, degranulation chemotaxis and phagocytosis regarding dysregulation of immune and inflammatory responses in the prefrontal cortex. Therefore, this study suggests that these FMRP-deficient DAPs in the prefrontal cortex might contribute to the etiology and pathogenesis of ASD in FXS.

Conventional protocols for proteomics analysis usually start by extracting or solubilizing the proteins from their substrates. This step can be challenging for archaeological proteins, when they are heavily contaminated or decayed. The remains of animal fur/leather objects from an early medieval burial in Trossingen (580 CE) from Southwest Germany were submitted to proteomics analysis for species identification. One leather sample (TS3) yielded enough proteins to be identified as cow using a urea-based extraction (method "U"), confirming the microscopic identification. But two other samples (TS1 and TS2), compacted in a greyish brittle matrix with embedded hair visible only under microscope, could not be characterized with that method. A series of tests was performed using reduction/alkylation with tris(2-carboxyethyl)phosphine/chloroacetamide at 95 °C directly on the matrix (method "95C"), with or without the use of paramagnetic beads as cleaning procedure (from the single-pot solid-phase-enhanced sample preparation or SP3). Hair keratins were best recovered in the fur samples when digestion was performed directly on the insoluble fraction after reduction/alkylation. For both samples TS1 and TS2, an ovicaprine species was identified, with TS1 firmly identified as sheep due to the exceptional preservation of keratins and keratin-associated proteins. The simplified protocol also showed improvements on the identification of collagen in the leather sample TS3. SIGNIFICANCE: North European burials had a strong tradition of bodies wrapped or covered in animal skins; textiles, furs, items of leather and other organic materials were essential parts of grave furnishings (as part of the deceased's clothing as well as grave goods) but are mostly only preserved as residues, uncharacterized layers or stains. Even well preserved finds like the waterlogged organic remains from Trossingen show strong limitations for visual identification. Because the traditional protocol was unable to extract proteins efficiently from the soil matrix in which the samples were embedded, a new method was devised that enabled the determination of the sampled fur remains as sheep and the leather fragments as cow leather. Analyses showed that the key step for accessing the proteins in the soiled archaeological samples was heating for 10 min at 95 °C with a solution of tris(2-carboxyethyl)phosphine/chloroacetamide (TCEP/CAA). The protocol proposed in this study offers to work on minute samples (1 mg of sample or less) and overcame the challenge of separating the proteins from their archaeological matrix. It offers interesting perspectives for archaeological sites or objects where clothing are suspected but hardly detectable, such as burial sites.

Non-small cell lung cancer (NSCLC) is associated with high morbidity and mortality. Propofol functions as a tumor-inhibitor drug by regulating microRNAs (miRNAs). The primary objective of this study is to explore the functional mechanism of propofol in cisplatin (Cis) resistance of NSCLC cells by regulating the miR-744-5p/miR-615-3p axis. Cis-resistant NSCLC cell lines were cultured and chemotherapy-resistance (CR) to Cis of NSCLC cells to Cis was confirmed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method, flow cytometry, and colony formation assay. Ferroptosis was evaluated by measurement of iron content, ferroptosis-related proteins (GPX4/ ACSL4/SLC7A11) and lipid peroxidation (SOD/GSH/MDA) through Western blot analysis and assay kits. After the dual-luciferase reporter assay to testify gene interactions, the functional rescue experiments and nude mouse tumor formation assay were performed. Based on results, propofol reduced IC50 value and CR of NSCLC cells to Cis and induced ferroptosis. Propofol upregulated miR-744-5p/miR-615-3p to inhibit GPX4 transcription. Upregulation of GPX4 or downregulation of miR-744-5p/miR-615-3p attenuated the inhibitory effect of propofol on CR to Cis. In vivo, propofol inhibited tumor growth and CR to Cis by upregulating miR-744-5p/miR-615-3p and inhibiting GPX4 to induce ferroptosis. In summary, propofol inhibited GPX4-mediated ferroptosis and reduces CR of NSCLC cells to Cis through the miR-744-5p/miR-615-3p axis. SIGNIFICANCE: To study the effect of propofol on chemoresistance of non-small cell lung cancer (NSCLC), and to provide a new theoretical basis for the treatment of NSCLC.

The central goal of this study was to investigate the alterations in transcriptome of testis in F1 generation adult rats exposed to carbimazole prenatally. At post-natal day 100, the testis of rats delivered to carbimazole exposed (time-mated pregnant rats orally administered with carbimazole from gestation day 9 to 21) and control (untreated pregnant rats) groups were subjected to transcriptomic analysis using NGS platform. A total of 187 differentially expressed (up regulated: 49 genes; down regulated: 138) genes were identified in carbimazole exposed rats over controls and the major processes associated with these altered testicular transcripts were examined. Functional clustering analysis suggest that the involvement of identified DEGs were linked to intrinsic and extrinsic apoptotic pathways, mitochondrial solute carriers slc25a members, nuclear receptors/zinc family members, steroidogenic pathway and cholesterol synthesis, and growth factors and protein kinases and thus represent potential mediators of the developmental toxic effects of carbimazole in F1 generation rats. Based on the findings, it can be concluded that prenatal exposure to carbimazole prominently affects expression of multiple transcripts implicating key regulatory events associated with testicular functions, spermatogenesis and steroidogenesis in rats at their adulthood. These results support our earlier findings and hypothesis. This background information obtained at the testicular transcriptome during gestational hypothyroidism might be helpful for future studies and experiments to gain additional in-depth analysis and to develop strategies to protect F1 generation male reproductive health. SIGNIFICANCE: The rationale for the paper described thyroid gland changes in the off springs. Antithyroid drugs are widely used to control thyroid disorders and used to control thyroid hormone levels during surgeries. Carbimazole is one of the antithyroid drugs and is a parent molecule of methimazole. Both the drugs can able to cross placenta. During fetal period, the development of thyroid gland is not completely formed and hence, the fetus entirely depends on the maternal thyroid hormones. Therefore, it is conceivable that the disturbances at the level of maternal thyroid hormones could interfere with the development of vital organs such as testis and glands including thyroid gland (Kala et al., 2012). To address this notion, the present study was designed and executed.