Dickkopf-Like1 Regulates Postpubertal Spermatocyte Apoptosis and Testosterone Production

Dakhova, Olga; O’Day, Diana R.; Kinet, Noe; Yucer, Nur; Wiese, Mary; Shetty, Gunapala; Ducy, Patricia

doi:10.1210/en.2008-0673

Cited by 22 publications

(14 citation statements)

References 34 publications

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“…This result is consistent with the observation that a murine homolog of DKK1 plays a role in testicular testosterone production [20]. DKK1 is expressed in a number of tissues including ovary, testis and adipose tissue, with increased expression in PCOS ovarian theca [4].…”

Section: Discussionsupporting

confidence: 92%

Harnessing Expression Data to Identify Novel Candidate Genes in Polycystic Ovary Syndrome

et al. 2011

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Novel pathways in polycystic ovary syndrome (PCOS) are being identified in gene expression studies in PCOS tissues; such pathways may contain key genes in disease etiology. Previous expression studies identified both dickkopf homolog 1 (DKK1) and DnaJ (Hsp40) homolog, subfamily B, member 1 (DNAJB1) as differentially expressed in PCOS tissue, implicating them as candidates for PCOS susceptibility. To test this, we genotyped a discovery cohort of 335 PCOS cases and 198 healthy controls for three DKK1 single nucleotide polymorphisms (SNPs) and four DNAJB1 SNPs and a replication cohort of 396 PCOS cases and 306 healthy controls for 1 DKK1 SNP and 1 DNAJB1 SNP. SNPs and haplotypes were determined and tested for association with PCOS and component phenotypes. We found that no single nucleotide polymorphisms were associated with PCOS risk; however, the major allele of rs1569198 from DKK1 was associated with increased total testosterone (discovery cohort P = 0.0035) and dehydroepiandrosterone sulfate (replication cohort P = 0.05). Minor allele carriers at rs3962158 from DNAJB1 had increased fasting insulin (discovery cohort P = 0.003), increased HOMA-IR (discovery cohort P = 0.006; replication cohort P = 0.036), and increased HOMA-%B (discovery cohort P = 0.004). Carriers of haplotype 2 at DNAJB1 also had increased fasting insulin, HOMA-IR, and HOMA-%B. These findings suggest that genetic variation in DKK1 and DNAJB1 may have a role in the hyperandrogenic and metabolic dysfunction of PCOS, respectively. Our results also demonstrate the utility of gene expression data as a source of novel candidate genes in PCOS, a complex and still incompletely defined disease, for which alternative methods of gene identification are needed.

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Section: Discussionsupporting

confidence: 92%

Harnessing Expression Data to Identify Novel Candidate Genes in Polycystic Ovary Syndrome

et al. 2011

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“…Dkkl1 mRNA expression was reported previously to be testis specific and restricted to the developing acrosome in mice (Kohn et al 2005), an observation which is consistent with the specific expression of the dkkl1 messenger in zone C and at the rear of spermatid heads from stages XI to XV, the stages of acrosome formation in the dogfish (Loir et al 1995). DKKL1 was also recently proposed to regulate spermatocyte apoptosis and testosterone production (Dakhova et al 2009). The spermatogenesis-and centriole-associated protein, also named speriolin, was shown to be testis specific and mainly expressed in spermatids in mice (Goto & Eddy 2004), findings which support our results.…”

Section: Relative Expression To Testissupporting

confidence: 75%

Stage-specific gene expression during spermatogenesis in the dogfish (Scyliorhinus canicula)

Redon¹,

Bosseboeuf²,

Rocancourt³

et al. 2010

Reproduction

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In the dogfish testis, the cystic arrangement and polarization of germ cell stages make it possible to observe all stages of spermatogenesis in a single transverse section. By taking advantage of the zonation of this organ, we have used suppressive subtractive libraries construction, real-time PCR, and in situ hybridization to identify 32 dogfish genes showing differential expressions during spermatogenesis. These include homologs of genes already known to be expressed in the vertebrate testis, but found here to be specifically expressed either in pre-meiotic and/or meiotic zones (ribosomal protein S8, high-mobility group box 3, ubiquitin carboxylterminal esterase L3, 20b-hydroxysteroid dehydrogenase, or cyclophilin B) or in post-meiotic zone (speriolin, Soggy, zinc finger protein 474, calreticulin, or phospholipase c-z). We also report, for the first time, testis-specific expression patterns for dogfish genes coding for A-kinase anchor protein 5, ring finger protein 152, or F-box only protein 7. Finally, the study highlights the differential expression of new sequences whose identity remains to be assessed. This study provides the first molecular characterization of spermatogenesis in a chondrichthyan, a key species to gain insight into the evolution of this process in gnathostomes.

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“…Caudal epididymides were minced in 1 ml PBS, and the number of cells released was counted after 1 h. The total sperm count was assessed in the final suspension by using a hemocytometer (Dakhova et al, 2009). Circulating leves of testosterone, estradiol (E2) and progesterone were measured by radioimmunoassay (RIA) from Diagnostic Systems Laboratories (Testosterone RIA DSL-4000, Estradiol RIA DSL-43100 and Progesterone RIA-3900).…”

Section: Methodsmentioning

confidence: 99%

Endocrine Regulation of Male Fertility by the Skeleton

Oury

Sumara

et al. 2011

Cell

Self Cite

571

634

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Although the endocrine capacity of bone is widely recognized, interactions between bone and the reproductive system have until now focused on the gonads as a regulator of bone remodeling. We now show that in males, bone acts as a regulator of fertility. Using co-culture assays, we demonstrate that osteoblasts are able to induce testosterone production by the testes, while they fail to influence estrogen production by the ovaries. Analyses of cell-specific loss- and gain-of-function models reveal that the osteoblast-derived hormone osteocalcin performs this endocrine function. By binding to a G-protein coupled receptor expressed in the Leydig cells of the testes, osteocalcin regulates in a CREB-dependent manner the expression of enzymes required for testosterone synthesis, promoting germ cell survival. This study expands the physiological repertoire of osteocalcin, and provides the first evidence that the skeleton is an endocrine regulator of reproduction.

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Dickkopf-Like1 Regulates Postpubertal Spermatocyte Apoptosis and Testosterone Production

Cited by 22 publications

References 34 publications

Harnessing Expression Data to Identify Novel Candidate Genes in Polycystic Ovary Syndrome

Harnessing Expression Data to Identify Novel Candidate Genes in Polycystic Ovary Syndrome

Stage-specific gene expression during spermatogenesis in the dogfish (Scyliorhinus canicula)

Endocrine Regulation of Male Fertility by the Skeleton

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