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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since the first "test tube" baby, Louise Brown, was born on July 25, 1978, there have been unbridled advances in the diagnosis and treatment of male infertility. There have now been more than 4 million individuals born using assisted reproductive technologies, with approximately 170,000 coming from donated oocytes and embryos. There have been many other significant achievements in the treatment of male infertility in recent decades, which are included in this review.
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PMID:Changes in male fertility in the last two decades. 2211 43

Prior to 1978, the therapeutic offerings available to couples afflicted with infertility were painfully limited. Indeed, there was precious little one could offer Lesley and John Brown in their desperation. Anovulatory infertility was managed with ovulation induction using Clomiphene Citrate and Human Menopausal Gonadotropins. Anatomic infertility was addressed by increasingly sophisticated if marginally effective microsurgical approaches. The therapy of male infertility, still in its infancy, was commonly handled through cervical or intrauterine insemination including the use of donor sperm. The road traveled by Mrs. Brown radically altered this hope-limited landscape. A trailblazer to the millions who followed, Mrs. Brown played a key role in the abolition of the scourge of infertility. In this communication we trace in some detail the singular story of Mrs. Lesley Brown and the all-important legacy thereof. In doing so, we wish to pay tribute to this remarkable individual and her contributions to one of the most compelling scientific and medical breakthroughs of the 20th century.
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PMID:Barrenness vanquished: the legacy of Lesley Brown. 2367 13

In the inbred SHR/OlaIpcv rat colony, we identified males with small testicles and inability to reproduce. By selectively breeding their parents, we revealed the infertility to segregate as an autosomal recessive Mendelian character. No other phenotype was observed in males, and females were completely normal. By linkage using a backcross with Brown Norway strain, we mapped the locus to a 1.2Mbp segment on chromosome 7, harboring 35 genes. Sequencing of candidate genes revealed a G to A substitution in a canonical 'AG' splice site of intron 37 in Sbf1 (SET binding factor 1, alias myotubularin-related protein 5). This leads to either skipping exon 38 or shifting splicing one base downstream, invariantly resulting in frameshift, premature stop codon and truncation of the protein. Western blotting using two anti-Sbf1 antibodies revealed absence of the full-length protein in the mutant testis. Testicles of the mutant males were significantly smaller compared with SHR from 4weeks, peaked at 84% wild-type weight at 6weeks and declined afterward to 28%, reflecting massive germ cell loss. Histological examination revealed lower germ cell number; latest observed germ cell stage were round spermatids, resulting in the absence of sperm in the epididymis (azoospermia). SBF1 is a member of a phosphatase family lacking the catalytical activity. It probably modulates the activity of a phosphoinositol phosphatase MTMR2. Human homozygotes or compound heterozygotes for missense SBF1 mutations exhibit Charcot-Marie-Tooth disease (manifested mainly as progressive neuropathy), while a single mouse knockout reported in the literature identified male infertility as the only phenotype manifestation.
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PMID:Splicing mutation in Sbf1 causes nonsyndromic male infertility in the rat. 2733 32