The mammary gland is a sensitive pubertal target in CD-1 and C57Bl/6 mice following perinatal perfluorooctanoic acid (PFOA) exposure

Perfluorooctanoic acid (PFOA) is a developmental toxicant in mice, with varied strain outcomes depending on dose and period of exposure. The impact of PFOA on female mouse pubertal development at low doses (≤1 mg/kg) has yet to be determined. Therefore, female offspring from CD-1 and C57Bl/6 dams exposed to PFOA, creating serum concentrations similar to humans, were examined for pubertal onset, including mammary gland development. Pups demonstrated a shorter PFOA elimination half-life than that reported for adult mice. Prenatal exposure to PFOA caused significant mammary developmental delays in female offspring in both strains. Delays started during puberty and persisted into young adulthood; severity was dose-dependent. Also an evaluation of female serum hormone levels and pubertal timing onset revealed no effects of PFOA compared to controls in either strain. These data suggest that the mammary gland is more sensitive to early low level PFOA exposures compared to other pubertal endpoints, regardless of strain.     

The effects of ALA-PDT on microbiota in pilosebaceous units of patients with severe acne: A metagenomic study

Background5-aminolevulinic acid mediated photodynamic therapy (ALA-PDT) is increasingly used to control severe acne. However, its impact on skin microbiota remains uncertain.ObjectivesWe aimed to compare the makeup, diversity, and function of the microbiota in pilosebaceous units of patients with severe acne before and after ALA-PDT.MethodsA longitudinal cohort study was performed on 11 participants with severe facial acne. All patients were given 5%ALA-PDT every two weeks for three sessions in total. The contents of lesions were sampled for metagenomic sequencing at baseline and two weeks after the first ALA-PDT session.ResultsCutibacterium acnes was the most dominant species followed by Staphylococcus epidermidis and Pseudomonas fluorescens. Treatment with ALA-PDT led to clinical improvements in acne severity concurrent with a significant reduction in the relative abundance of C. acnes, while P. fluorescens increased significantly after ALA-PDT. No significant change was identified in other species. ALA-PDT administration was associated with an increased microbiota diversity and reductions in the relative abundance of the functional genes involved in energy metabolism and DNA replication.ConclusionsALA-PDT plays a therapeutic role by killing C. acnes, increasing P. fluorescens and the microbiome diversity, while inhibiting the function of microbiota in pilosebaceous units of severe acne.     

Transplantation of bone marrow mesenchymal stem cells on collagen scaffolds for the functional regeneration of injured rat uterus

Serious injuries of endometrium in women of reproductive age are often followed by uterine scar formation and a lack of functional endometrium predisposing to infertility or miscarriage. Bone marrow-derived mesenchymal stem cells (BM-MSCs) have shown great promise in clinical applications. In the present study, BM-MSCs loaded onto degradable collagen membranes were constructed. Collagen membranes provided 3-dimmensional architecture for the attachment, growth and migration of rat BM-MSCs and did not impair the expression of the stemness genes. We then investigated the effect of collagen/BM-MSCs constructs in the healing of severe uterine injury in rats (partial full thickness uterine excision). At four weeks after the transplantation of collagen/BM-MSCs constructs, BM-MSCs were mainly located to the basal membrane of regenerative endometrium. The wounded tissue adjacent to collagen/BM-MSCs constructs expressed higher level of bFGF, IGF-1, TGFβ1 and VEGF than the corresponding tissue in rats receiving collagen construct alone or in spontaneous regeneration group. Moreover, the collagen/BM-MSCs system increased proliferative abilities of uterine endometrial and muscular cells, facilitated microvasculature regeneration, and restored the ability of endometrium to receive the embryo and support its development to a viable stage. Our findings indicate that BM-MSCs may support uterine tissue regeneration.     

多囊卵巢综合征神经内分泌病因机制的研究进展

多囊卵巢综合征(PCOS)是女性常见的生殖内分泌疾病,PCOS的典型特征是高雄激素血症、排卵障碍和卵巢多囊样改变.高雄激素血症通常是由垂体黄体生成激素(LH)脉冲分泌增加所致.多数PCOS女性表现为血清LH水平升高,LH脉动分泌频率升高.LH脉动分泌频率异常升高反映了促性腺激素释放激素(GnRH)神经回路异常活跃,提示...     

Les mélanomes du tronc ont-ils un pronostic individualisable? À propos d'une série de 77 cas

AimsTruncal melanoma is characterized by lymphatic drainage to single or multiple basins, affecting different anatomic regions. Since the introduction of sentinel lymph node biopsy (SLN) several questions have aroused in regard to this particular drainage. However, published data available on SLN anatomic distribution and on the prognostic value of multiple-nodal drainage is controversial. The aim of the present study was to provide further evidence based on our own experience.MethodsFrom January 2003 through December 2006, a total of 77 melanoma of the trunk were diagnosed and treated at our institution. Systematic lymphoscintigraphy was obtained for all patients, followed by removal of SLN and in-transit lesions. When SLN metastasis was detected a complete lymphadenectomy was performed and adjuvant immunotherapy with interferon was administered. Statistical analysis was performed using Chi² and Fisher's exact tests for categoric variables and Kaplan-Meier curves for survival.ResultsLymphoscintigraphy visualized 70.1% of single and 28.6% of multiple-nodal drainage (uninterpretable data). The rate of SLN macrometastasis ranged from 7.8 to 14.3%. Micrometastasis were found in 6.5% of patients. Positive SLN were discovered in 12.9% (17/54) of single-nodal and 18.6% (2/22) of multiple-nodal drainage. Melanoma's topography significantly influenced lymphatic drainage distribution, with 28.6% of single-nodal and 71.4% of multiple-nodal drainage for central tumors, and with 79.4% of single-nodal and 19.1% of multiple-nodal drainage for lateral tumors. The group with multiple-nodal drainage was associated non-significantly with primary tumor ulceration, 39 vs 24%. The Breslow thickness did not associate to multiple-nodal drainage. There were no differences in the rate of lymph node metastasis between both groups, 18 vs 12.9%. After a median follow-up of 47 months, prognosis was similar regardless of SLN status, with 80.3% overall survival for negative SLN and 81.3% for positive SLN. Single or multiple drainage did not affect survival rates significantly, with 84% survival for single-nodal drainage and 95% for multiple-nodal drainage.ConclusionsPrimary tumor location (medial location) was the principal risk factor for multi-nodal drainage: lymphoscintigraphy was the best technique for lymphatic drainage assessment. Primary tumor location with single or multi-nodal drainage did not influence the rate of positive SLN and had similar disease-free and overall survival. For us, truncal melanoma has not a different prognosis than melanoma of extremities.     

Polygenic risk scores and risk-stratified breast cancer screening: Familiarity and perspectives of health care professionals

PurposeHealth care professionals are expected to take on an active role in the implementation of risk-based cancer prevention strategies. This study aimed to explore health care professionals’ (1) self-reported familiarity with the concept of polygenic risk score (PRS), (2) perceived level of knowledge regarding risk-stratified breast cancer (BC) screening, and (3) preferences for continuing professional development.MethodsA cross-sectional survey was conducted using a bilingual—English/French—online questionnaire disseminated by health care professional associations across Canada between November 2020 and May 2021.ResultsA total of 593 professionals completed more than 2 items and 453 responded to all questions. A total of 432 (94%) participants were female, 103 (22%) were physicians, and 323 (70%) were nurses. Participants reported to be unfamiliar with (20%), very unfamiliar (32%) with, or did not know (41%) the concept of PRS. Most participants reported not having enough knowledge about risk-stratified BC screening (61%) and that they would require more training (77%). Online courses and webinar conferences were the preferred continuing professional development modalities.ConclusionThe study indicates that health care professionals are currently not familiar with the concept of PRS or a risk-stratified approach for BC screening. Online information and training seem to be an essential knowledge transfer modality.     

Heterozygous loss-of-function variants in LHX8 cause female infertility characterized by oocyte maturation arrest

PurposeThe genetic causes of oocyte maturation arrest leading to female infertility are largely unknown, and no population-based genetic analysis has been applied in cohorts of patients with infertility. We aimed to identify novel pathogenic genes causing oocyte maturation arrest by using a gene-based burden test.MethodsThrough comparison of exome sequencing data from 716 females with infertility characterized by oocyte maturation arrest and 3539 controls, we performed a gene-based burden test and identified a novel pathogenic gene LHX8. Splicing event was evaluated using a minigene assay, expression of LHX8 protein was assessed in HeLa cells, and nuclear subcellular localization was determined in both HeLa cells and mouse oocytes.ResultsA total of 5 heterozygous loss-of-function LHX8 variants were identified from 6 independent families (c.389+1G>T, c.412C>T [p.Arg1381], c.282C>A [p.Cys941]; c.257dup [p.Tyr861]; and c.180del, [p.Ser61Profs130]). All the identified variants in LHX8 produced truncated LHX8 protein and resulted in loss of LHX8 nuclear localization in both HeLa cells and mouse oocytes.ConclusionBy combining genetic evidence and functional evaluations, we identified a novel pathogenic gene LHX8 and established the causative relationship between LHX8 haploinsufficiency and female infertility characterized by oocyte maturation arrest.