Multi-omic analysis of gametogenesis reveals a novel signature at the promoters and distal enhancers of active genes.

Epigenetic regulation of gene expression is tightly controlled by the dynamic modification of histones by chemical groups, the diversity of which has largely expanded over the past decade with the discovery of lysine acylations, catalyzed from acyl-coenzymes A. We investigated the dynamics of lysine acetylation and crotonylation on histones H3 and H4 during mouse spermatogenesis. Lysine crotonylation appeared to be of significant abundance compared to acetylation, particularly on Lys27 of histone H3 (H3K27cr) that accumulates in sperm in a cleaved form of H3. We identified the genomic localization of H3K27cr and studied its effects on transcription compared to the classical active mark H3K27ac at promoters and distal enhancers. The presence of both marks was strongly associated with highest gene expression. Assessment of their co-localization with transcription regulators (SLY, SOX30) and chromatin-binding proteins (BRD4, BRDT, BORIS and CTCF) indicated systematic highest binding when both active marks were present and different selective binding when present alone at chromatin. H3K27cr and H3K27ac finally mark the building of some sperm super-enhancers. This integrated analysis of omics data provides an unprecedented level of understanding of gene expression regulation by H3K27cr in comparison to H3K27ac, and reveals both synergistic and specific actions of each histone modification.

Usefulness of early morphological ultrasound in association with cell-free DNA testing in case of atypical serum markers in first trimester of pregnancy: A retrospective study over 5 years.

BACKGROUND: Early morphologic ultrasound, generally carried out in case of atypical first trimester serum markers (PAPP-A and/or free hCGß <0.30 MoM), has not been re-evaluated since the possibility of performing a cell-free fetal DNA analysis in this indication. Our objective was to evaluate the usefulness of early morphological ultrasound in case of atypical profile of serum markers performed in association with Non-Invasive Prenatal Testing (NIPT). METHODS: This was a single-center retrospective study in a tertiary maternity. Between January 2017 and December 2021, women with an atypical first trimester serum markers and low/intermediate risk for trisomy 21 (<1/50) were included. The clinical data, results of first trimester serum markers, NIPT, early morphological ultrasound and subsequent ultrasounds and other investigations (amniocentesis, pregnancy outcomes) were analyzed. RESULTS: After exclusion of women with high-risk of trisomy 21 and lost to follow-up, 163 women were included. In 72 % of cases (117/163), women had a low risk of trisomy 21, and 39 % (59/163) had an early morphological ultrasound. Early morphological ultrasound was useful to detect severe IUGR leading to the suspicion of triploidy (3/163, 1.8 %). In all other situations, it did not allow earlier management. After analysis of the 3 triploidy cases, a collapsed profile for both serum markers was demonstrated (<0.25 MoM). CONCLUSIONS: Systematic early morphological ultrasound in case of an atypical serum marker profile seems useless considering the performance of NIPT. An ultrasound restricted to women with both markers below 0.25 MoM would allow the early detection of triploidy.

Fertility preservation in young men with Klinefelter syndrome: A systematic review.

BACKGROUND: Klinefelter syndrome (KS) is the most common cause of genetic male infertility, as most patients present azoospermia. In the testis, a massive decrease in the number of germinal cells is observed and this can begin early in childhood. Thus, it is possible to collect spermatozoa after sperm collection or thanks to testicular sperm extraction (TESE), but the chances finding spermatozoa are decreasing with the age. Sperm collection or TESE should be performed as early as possible. When KS is diagnosed during childhood or teens, fertility preservation could be beneficial. The minimal age for proposing fertility preservation remains controversial and there is no current recommendation about fertility preservation in young men with KS. DESIGN: In this context, we have conducted a systematic review of the results of fertility preservation in young patients with KS to discuss the optimal age range for offering fertility preservation, including or not a TESE. RESULTS: Six articles were included in the systematic review, with patients between 13 and 24 years-old. Except for one, all young men agreed for sperm collection following masturbation. Azoospermia was diagnosed in all patients presenting homogenous KS. One study reported the presence of spermatozoa in the ejaculate of a young man with mosaic KS. Fifty-eight young man for whom ejaculated sperm collection was unsuccessful have benefited from TESE. Testicular spermatozoa were found and frozen in 27 patients out of the 58 (46.5%). The chances of freezing viable testicular sperm between 14 and 23 years of age do not appear to depend on age. CONCLUSION: Fertility preservation should be proposed in young men, but the optimal age for proposing the first sperm collection could be adapted according to the medical context and the psychological maturity of the young man.