DNMT3L Is a Regulator of X Chromosome Compaction and Post-Meiotic Gene Transcription

Previous studies on the epigenetic regulator DNA methyltransferase 3-Like (DNMT3L), have demonstrated it is an essential regulator of paternal imprinting and early male meiosis. Dnmt3L is also a paternal effect gene, i.e., wild type offspring of heterozygous mutant sires display abnormal phenotypes suggesting the inheritance of aberrant epigenetic marks on the paternal chromosomes. In order to reveal the mechanisms underlying these paternal effects, we have assessed X chromosome meiotic compaction, XY chromosome aneuploidy rates and global transcription in meiotic and haploid germ cells from male mice heterozygous for Dnmt3L. XY bodies from Dnmt3L heterozygous males were significantly longer than those from wild types, and were associated with a three-fold increase in XY bearing sperm. Loss of a Dnmt3L allele resulted in deregulated expression of a large number of both X-linked and autosomal genes within meiotic cells, but more prominently in haploid germ cells. Data demonstrate that similar to embryonic stem cells, DNMT3L is involved in an auto-regulatory loop in germ cells wherein the loss of a Dnmt3L allele resulted in increased transcription from the remaining wild type allele. In contrast, however, within round spermatids, this auto-regulatory loop incorporated the alternative non-coding alternative transcripts. Consistent with the mRNA data, we have localized DNMT3L within spermatids and sperm and shown that the loss of a Dnmt3L allele results in a decreased DNMT3L content within sperm. These data demonstrate previously unrecognised roles for DNMT3L in late meiosis and in the transcriptional regulation of meiotic and post-meiotic germ cells. These data provide a potential mechanism for some cases of human Klinefelter's and Turner's syndromes

Nerve sparing can preserve orgasmic function in most men after robotic-assisted laparoscopic radical prostatectomy.

OBJECTIVE: •  To investigate orgasmic outcomes in patients undergoing robotic-assisted laparoscopic radical prostatectomy (RALP) and the effects of age and nerve sparing on these outcomes. PATIENTS AND METHODS: •  Between January 2005 and June 2007, 708 patients underwent RALP at our institution. •  We analysed postoperative potency and orgasmic outcomes in the 408 men, of the 708, who were potent, able to achieve orgasm preoperatively and available for follow-up. RESULTS: •  Of men aged ≤60 years, 88.4% (198/224) were able to achieve orgasm postoperatively in comparison to 82.6% (152/184) of older men (P < 0.001). •  Of patients who received bilateral nerve sparing (BNS) during surgery, 273/301 (90.7%) were able to achieve orgasm postoperatively compared with 46/56 (82.1%) patients who received unilateral nerve sparing and 31/51 (60.8%) men who received non-nerve-sparing surgery (P < 0.001). •  In men ≤60 years who also underwent BNS, decreased sensation of orgasm was present in 3.2% of men, and postoperative orgasmic rates were significantly better than men ≤60 years who underwent unilateral or no nerve sparing (92.9% vs 83.3% vs 65.4%, respectively; P < 0.001). •  Potency rates were also significantly higher in men ≤60 years and in those who underwent BNS. CONCLUSIONS: •  Age and nerve sparing influence recovery of orgasm and erectile function after RALP. •  Men ≤60 years old and those who undergo BNS are most likely to maintain normal sexual function