Abstract:
:We aimed to survey the monogenic causes of disorders of sex development (DSD) and thereby its prevalence in India. This study revealed mutations resulting in androgen insensitivity syndrome, 5α-reductase type 2 deficiency, and gonadal dysgenesis were commonly reported. Intriguingly, AR deficits were the most prevalent (32 mutations) and of 11/26 missense mutations were in exons 4-8 (encoding ligand binding domain). The unique features of SRD5A2 defects were p.R246Q (most prevalent) and p.G196S could be mutational hotspots, dual gene defects (p.A596T in AR and p.G196S in SRD5A2) in a patient with hypospadias and novel 8 nucleotide deletion (exon 1) found in a patient with perineal hypospadias. Deficits in SRY, WT1, DHH, NR5A1, and DMRT1 caused 46,XY gonadal dysgenesis. Notably, mutations in AR, SRD5A2, MAMLD1, WT1, and MAP3K1 have led to hypospadias and only one CYP19A1 mutation caused aromatase deficiency was reported to date. Data mining from various databases has not only reinforced the role of well-established genes (e.g., SRY, WT1, DHH, NR5A1, DMRT1, AR, SRD5A2, MAMLD1) involved in DSD but also provided us 12 more potential candidate genes (ACVR1, AMHR2, CTNNB1, CYP11A1, CYP19A1, FGFR2, FGF9, PRKACA, PRKACG, SMAD9, TERT, ZFPM2), which benefit from a close association with the well-established genes involved in DSD and might be useful to screen owing to their direct gene-phenotype relationship or through direct functional interaction. As more genes have been revealed in relation to DSD, we believe ultimately it holds a better scenario for therapeutic regimen. Despite the advances in translational medicine, hospitals are yet to adopt genetic testing and counseling facilities in India that shall have potential impact on clinical diagnosis. Abbreviations: 5α-RD2: 5α-Reductase type 2; AIS: androgen insensitivity syndrome; AMH: antimullerian hormone; AMHR: antimullerian hormone receptor; AR: androgen receptor gene; CAH: congenital adrenal hyperplasia; CAIS: complete AIS; CAH: congenital adrenal hyperplasia; CHH: congenital hypogonadotropic hypogonadism; CXORF6: chromosome X open reading frame 6 gene; CYP19A1: cytochrome P450 family 19 subfamily A member 1 gene; DHT: dihydrotestosterone; DMRT1: double sex and mab-3 related transcription factor 1 gene; DSD: disorders of sexual development; GD: gonadal dysgenesis; HGMD: human gene mutation database; IH: isolated hypospadias; MAMLD1: mastermind like domain containing 1 gene; MIS: mullerian inhibiting substance; NTD: N-terminal domain; OT DSD: ovotesticular DSD; PAIS: partial AIS; SOX9: SRY-related HMG-box 9 gene; SRY: sex-determining region Y gene; STAR: steroidogenic acute regulatory protein gene; SRD5A2: steroid 5 alpha-reductase 2 gene; T DSD: testicular DSD; T: testosterone; WNT4: Wnt family member 4 gene; WT1: Wilms tumor 1 gene; Δ4: androstenedione.
journal_name
Syst Biol Reprod Medjournal_title
Systems biology in reproductive medicineauthors
Nagaraja MR,Gubbala SP,Delphine Silvia CRW,Amanchy Rdoi
10.1080/19396368.2018.1549619subject
Has Abstractpub_date
2019-04-01 00:00:00pages
105-120issue
2eissn
1939-6368issn
1939-6376journal_volume
65pub_type
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journal_title:Systems biology in reproductive medicine
pub_type: 杂志文章
doi:10.1080/19396368.2017.1291767
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abstract::The aim of this study was to evaluate the feasibility and efficiency of using a sucrose gradient-based warming protocol as a universal warming approach on human cleavage stage embryos. Between January 2013 and November 2014, a total of 118 warming cycles were performed on 705 embryos which had previously been cryopres...
journal_title:Systems biology in reproductive medicine
pub_type: 杂志文章
doi:10.1080/19396368.2018.1487477
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abstract::Assessment of sperm DNA damage has been suggested as a negative predictor of fertility potential. Multiple pathological factors acting at both the intra-testicular and post-testicular levels may contribute to sperm DNA damage. The relative contribution of each of these factors in an individual with high DNA damage (>3...
journal_title:Systems biology in reproductive medicine
pub_type: 杂志文章
doi:10.1080/19396360902787944
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abstract::We have earlier shown that cobalt chloride (CoCl2)-induced hypoxia and second messenger 8-bromoadenosine 3', 5'-cyclic adenosine monophosphate (8-Br-cAMP) stimulates vascular endothelial growth factor (VEGF) production in Leydig tumor cell derived MA-10 cells. Both stimuli follow common signal transduction pathways in...
journal_title:Systems biology in reproductive medicine
pub_type: 杂志文章
doi:10.3109/19396368.2013.861034
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journal_title:Systems biology in reproductive medicine
pub_type: 杂志文章
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abstract::Increased trophoblast apoptosis has been implicated in pregnancies complicated by fetal growth restriction and preeclampsia (EC). We investigated placenta growth factor (PLGF) signaling during trophoblast apoptosis in culture and X-linked inhibitor of apoptosis protein (XIAP) and apoptosis inducible factor (AIF) in th...
journal_title:Systems biology in reproductive medicine
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更新日期:2014-10-01 00:00:00
abstract::FSH in infertile patients may be measured in the normal range and abnormal semen analysis findings may be observed in patients with normal FSH values. A recent study predicts that the sperm morphology and concentration may be impaired if the FSH value is above 4.5 IU/L. Therefore, this study aimed to define a clinical...
journal_title:Systems biology in reproductive medicine
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journal_title:Systems biology in reproductive medicine
pub_type: 杂志文章,评审
doi:10.3109/19396360903244598
更新日期:2010-04-01 00:00:00
abstract::To date we have yet to examine whether amino acid (AA) transport in human ovarian follicles is affected by competitive inhibition. In contrast, transplacental transfer of AAs in late-gestation sheep is characterized by reciprocal competition. This phenomenon has been described by algebraic equations of umbilical uptak...
journal_title:Systems biology in reproductive medicine
pub_type: 杂志文章
doi:10.1080/19396368.2017.1341962
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journal_title:Systems biology in reproductive medicine
pub_type: 杂志文章
doi:10.1080/19396368.2019.1666436
更新日期:2019-12-01 00:00:00
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journal_title:Systems biology in reproductive medicine
pub_type: 杂志文章
doi:10.3109/19396368.2012.655403
更新日期:2012-06-01 00:00:00
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journal_title:Systems biology in reproductive medicine
pub_type: 杂志文章
doi:10.3109/19396368.2012.743198
更新日期:2013-04-01 00:00:00
abstract::We aimed to assess the possible presence of a seasonal pattern in three parameters of semen analysis: sperm concentration, morphology, and motility as a function of the time of ejaculation and sperm production (spermatogenesis) in normal and oligozoospermic men. This retrospective study included a consecutive series o...
journal_title:Systems biology in reproductive medicine
pub_type: 杂志文章
doi:10.1080/19396368.2016.1225322
更新日期:2016-12-01 00:00:00
abstract::The GIRK2-containing inward-rectifying K(+) ion channels have been implicated in mammalian spermatogenesis. While the Girk2 null mice are fertile, the male weaver transgenic mice carrying a gain-of-function mutation in the Girk2 gene are infertile. To establish the exact period of spermatogenesis affected by this muta...
journal_title:Systems biology in reproductive medicine
pub_type: 杂志文章
doi:10.3109/19396368.2011.631685
更新日期:2011-12-01 00:00:00
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journal_title:Systems biology in reproductive medicine
pub_type: 杂志文章
doi:10.3109/19396368.2013.766281
更新日期:2013-06-01 00:00:00
abstract::Spermatozoa contain a complex population of RNAs including messenger RNAs (mRNAs) and small RNAs such as microRNAs (miRNA). It has been reported that these RNAs can be used to understand the mechanisms by which toxicological exposure affects spermatogenesis. The aim of our study was to compare mRNA and miRNA profiles ...
journal_title:Systems biology in reproductive medicine
pub_type: 杂志文章
doi:10.3109/19396368.2015.1022835
更新日期:2015-06-01 00:00:00
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journal_title:Systems biology in reproductive medicine
pub_type: 杂志文章
doi:10.1080/19396368.2020.1793032
更新日期:2020-10-01 00:00:00
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journal_title:Systems biology in reproductive medicine
pub_type: 杂志文章
doi:10.3109/19396368.2014.889774
更新日期:2014-06-01 00:00:00
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journal_title:Systems biology in reproductive medicine
pub_type: 杂志文章
doi:10.3109/19396368.2014.894152
更新日期:2014-06-01 00:00:00
abstract::In this retrospective study the outcomes of two protocols of controlled ovarian hyperstimulation and natural cycle in poor ovarian responders defined according to the Bologna criteria were compared to elucidate which approach is more suitable for the treatment of these patients. We comparatively analyzed 142 cycles of...
journal_title:Systems biology in reproductive medicine
pub_type: 杂志文章
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更新日期:2016-08-01 00:00:00
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journal_title:Systems biology in reproductive medicine
pub_type: 杂志文章
doi:10.1080/19396368.2016.1232447
更新日期:2016-12-01 00:00:00
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journal_title:Systems biology in reproductive medicine
pub_type: 杂志文章
doi:10.3109/19396368.2015.1040137
更新日期:2015-01-01 00:00:00
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journal_title:Systems biology in reproductive medicine
pub_type: 杂志文章
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更新日期:2020-12-01 00:00:00
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journal_title:Systems biology in reproductive medicine
pub_type: 杂志文章
doi:10.3109/19396368.2014.948102
更新日期:2014-12-01 00:00:00
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journal_title:Systems biology in reproductive medicine
pub_type: 杂志文章,评审
doi:10.3109/19396368.2012.691943
更新日期:2012-08-01 00:00:00
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journal_title:Systems biology in reproductive medicine
pub_type: 杂志文章,评审
doi:10.3109/19396361003653311
更新日期:2010-06-01 00:00:00
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journal_title:Systems biology in reproductive medicine
pub_type: 杂志文章
doi:10.1080/19396368.2018.1519047
更新日期:2019-06-01 00:00:00
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journal_title:Systems biology in reproductive medicine
pub_type: 杂志文章
doi:10.3109/19396368.2015.1041622
更新日期:2015-01-01 00:00:00
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journal_title:Systems biology in reproductive medicine
pub_type: 杂志文章
doi:10.1080/19396368.2016.1272648
更新日期:2017-04-01 00:00:00
abstract::A very common conception about the function of the spermatozoon is that its unique role is to transmit the paternal genome to the next generation. Most of the sperm genome is known to be condensed in many species by protamines, which are small and extremely positively charged proteins (50-70% arginine) with the functi...
journal_title:Systems biology in reproductive medicine
pub_type: 杂志文章
doi:10.1080/19396368.2018.1482383
更新日期:2018-12-01 00:00:00