IntroductionThe prevalence of diminished ovarian reserve (DOR), a common gynaecological disorder, is approximately 10% across the world. Failure in early diagnosis and treatment may result in continuous decreases in ovarian function and the resultant loss in an opportunity of pregnancy, which greatly affects the happiness of the women’s family and women’s physical and mental health. Nevertheless, there has been no effective treatment for such a disorder until now. Folic acid, a member of the vitamin B family, is involved in one-carbon cycle and methylation regulation. It has been found that folic acid affects the whole period of pregnancy, and folic acid supplementation has shown effective to remarkably reduce the incidence of fetal neural tube defects and decrease plasma homocysteic acid levels, thereby resulting in a decline in the incidence of abortion. In addition, folic acid is reported to mediate ovarian functions. It is therefore hypothesised that folic acid may improve DOR.Methods and analysisA single-centre, open-label, randomised, placebo-controlled clinical trial is designed. We plan to recruit 140 women with DOR at ages of 30–35 years. All participants will be randomised into the folic acid group and placebo group, and each subject will be given a tablet with the same appearance daily for 6 months. The primary outcome is antral follicle count, and the secondary outcomes are ovarian reserve markers, ovarian low-dose stimulation responses and safety.Ethics and disseminationThis study was approved by the Ethics Review Committee of Nanping First Hospital Affiliated to Fujian Medical University on 10 February 2021 (approval number: NPSY202002042). Written informed consent was obtained from all participants prior to randomisation, following a detailed description of the purpose of the study. The results of this clinical trial will be presented at scientific conferences and submitted to a peer-reviewed journal.Trial registration numberChinese Clinical Trial Registry, ChiCTR2100047410.

Abstract This abstract was not presented at the conference. Citation Format: Liang Y, Chen X, Zhan W, Zhu Y, Wu J, Huang O, He J, Zhu L, Li Y, Chen W, Shen K. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-08.

Abstract This abstract was not presented at the conference. Citation Format: Liang Y, Chen X, Zhan W, Yao J, Wu J, Huang O, He J, Zhu L, Li Y, Chen W, Shen K. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-13.

Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a multifunctional cytokine that acts through its receptor fibroblast growth factor-inducible 14 (Fn14). Recent studies demonstrated that the TWEAK/Fn14 signals participate in the development of psoriasis. The purpose of this study was to further explore the effect of Fn14 inhibition on experimental psoriasis. Psoriasis-like skin disease was induced in the wild-type and Fn14-knockout BALB/c mice. We found that Fn14 deficiency ameliorates psoriasis-like lesion in this model, accompanied by less inflammatory cell infiltration and proinflammatory cytokine production in lesional skin. The cutaneous expression of TNF receptor type 2 also decreased in the Fn14-deficient mice. Moreover, the topical application of TWEAK exacerbated psoriatic lesion in the wild-type but not in the Fn14-deficient mice. Furthermore, TWEAK promoted the expression of interleukin 8, keratin 17, and epidermal growth factor receptor (EGFR) but inhibited the expression of involucrin in psoriatic keratinocytes in vitro. Interestingly, such effect of TWEAK was abrogated by an EGFR inhibitor (erlotinib). TWEAK also enhances the proliferation and interleukin-6 production of dermal microvascular endothelial cells under psoriatic condition. In conclusion, TWEAK/Fn14 signals contribute to the development of psoriasis, and involves the modulation of resident cells and the transduction of the EGFR pathway. Fn14 inhibition might be a novel therapeutic strategy for patients with psoriasis.

Spermatozoa morphology, an important parameter in a semen specimen's potential fertility evaluation, is a significant factor for in vitro fertilisation in assisted reproductive technology. Eleven sterile men with headless spermatozoa, a type of human teratozoospermia, are presented. Their ejaculates' headless spermatozoa percentages were high with rare normal spermatozoa forms. Additionally, abnormal morphology (e.g. round-headed or microcephalic spermatozoa) was also found. Spermatozoa motility was somewhat affected, potentially because of the missing mitochondrial sheath at the sperm tail base. Patients who underwent assisted reproductive technology treatment experienced adverse pregnancy outcomes. Work types and corresponding environments seemed irrelevant, but specific family history may have prompted its genetic origin. Computer-assisted semen analysis systems easily mistake headless spermatozoa as oligozoospermia because of nonrecognition of the loose head. However, morphological testing, especially with an electronic microscope, clearly identifies abnormal spermatozoa. Future exploration requires more methods investigating the frequency and percentage of this morphological abnormality in different populations with varied fertility levels. Such research would estimate the probable correlation of the abnormality with other semen parameters and examine the potential developmental or genetic origins. During clinical work, medical staff should detect these cases, avoid misdiagnosis and provide proper consultation about diagnosis and assisted reproductive technology treatment.

© 2008 The Authors JEADV 2009, 23, 169–243 Journal compilation © 2008 European Academy of Dermatology and Venereology References 1 Mehta RK, Burrows NP, Rowland Payne CME, Mendelsohn MM, Pope FM, Rytina E. Elastosis perforans serpiginosa and associated disorders. Clin Exp Dermatol 2001; 26: 521–524. 2 Vearrier D, Buka RL, Roberts B, Cunningham B, Eichenfield L, Friedlander S. What is the standard of care in the evaluation of elastosis perforans serpiginosa? A survey of pediatric dermatologists. Pediatric Dermatol 2006; 23: 219–224. 3 O’Donnell B, Kelly P, Dervan P, Powell FC. Generalised elastosis perforans serpiginosa in Down’s syndrome. Clin Exp Dermatol 1992; 17: 31–33. 4 Rauch F, Glorieux FH. Osteogenesis imperfecta. Lancet 2004; 363: 1377–1385. 5 Huber MA. Osteogenesis imperfecta. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007; 103: 314–320. 6 Plotkin H. Syndromes with congenital brittle bones. BMC Pediatrics 2004; 4: 16. 7 Carey T. Elastosis perforans serpiginosa. Arch Dermatol 1977; 113: 1444–1445. 8 Reed W, Pidgeon J. Elastosis perforans serpiginosa with osteogenesis imperfecta. Arch Dermatol 1964; 89: 342–344.

Journal Article Mutations of KRT6A are more frequent than those of KRT16 in pachyonychia congenita type 1: report of a novel and a recently reported mutation in two unrelated Chinese families Get access Z‐L. Bai, Z‐L. Bai Department of Dermatology, the Second Hospital, Xi’an Jiaotong University, 157 Xiwu Road, Xi’an, Shaanxi 710004, China Search for other works by this author on: Oxford Academic Google Scholar Y‐G. Feng, Y‐G. Feng Department of Dermatology, the Second Hospital, Xi’an Jiaotong University, 157 Xiwu Road, Xi’an, Shaanxi 710004, China Correspondence: Yi‐Guo Feng. E‐mail: fengyiguo70@163.com Search for other works by this author on: Oxford Academic Google Scholar S‐S. Tan, S‐S. Tan Department of Dermatology, the Second Hospital, Xi’an Jiaotong University, 157 Xiwu Road, Xi’an, Shaanxi 710004, China Search for other works by this author on: Oxford Academic Google Scholar X‐Y. Wang, X‐Y. Wang Institute of Urology, Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education, Xi’an Jiaotong University, Xi'an, Shaanxi, China Search for other works by this author on: Oxford Academic Google Scholar S‐X. Xiao, S‐X. Xiao Department of Dermatology, the Second Hospital, Xi’an Jiaotong University, 157 Xiwu Road, Xi’an, Shaanxi 710004, China Search for other works by this author on: Oxford Academic Google Scholar H. Wang, H. Wang Department of Dermatology, the Second Hospital, Xi’an Jiaotong University, 157 Xiwu Road, Xi’an, Shaanxi 710004, China Search for other works by this author on: Oxford Academic Google Scholar H‐Q. Jia, H‐Q. Jia Institute for Nutritional Sciences, Chinese Academy of Sciences, Shanghai, China Search for other works by this author on: Oxford Academic Google Scholar J‐W. Wu, J‐W. Wu Department of Dermatology, the Second Hospital, Xi’an Jiaotong University, 157 Xiwu Road, Xi’an, Shaanxi 710004, China Search for other works by this author on: Oxford Academic Google Scholar D‐L. He, D‐L. He Institute of Urology, Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education, Xi’an Jiaotong University, Xi'an, Shaanxi, China Search for other works by this author on: Oxford Academic Google Scholar R‐H. Kang R‐H. Kang Department of Dermatology, the Fourth Clinical Medical College of Hebei Medical University, Shijiazhuang, China Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 159, Issue 1, 1 July 2008, Pages 238–240, https://doi.org/10.1111/j.1365-2133.2008.08603.x Published: 01 July 2008

The objective of this study was to assess fertilization and embryonic development following intracytoplasmic sperm injection (ICSI) of oocytes from porcine preantral follicles matured in vitro. Also, another aim was to describe actin filament distribution during fertilization and embryonic development of those oocytes after ICSI as one of the factors assessed. Preantral follicles isolated from prepubertal porcine ovaries were cultured in a system that supports follicular development. After in vitro maturation, the oocytes were fertilized by ICSI or conventional fertilization in vitro (IVF). Actin filaments of the fertilized oocytes and embryos produced by ICSI or IVF were stained by rhodamine-phalloidin and visualized by fluorescence microscopy. ICSI resulted in 64% fertilization of porcine preantral follicle oocytes matured in vitro. Of those, 51% of the fertilized oocytes cleaved and 21% developed to the blastocyst stage. No significant differences in percentages of oocyte fertilization, cleavage, and blastocyst formation were observed between ICSI and IVF (53%, 45% and 16%, respectively). Actin filament distribution during fertilization and embryonic development of ICSI- or IVF-fertilized oocytes from porcine preantral follicles was similar to that of oocytes derived from antral follicles and fertilized by standard IVF. These results indicate that oocytes from porcine preantral follicles matured in vitro following ICSI can undergo fertilization and subsequent embryonic development.

This study was conducted to identify an in vitro culture system that would support intact porcine follicle growth from preantral follicle to antral stages, oocyte maturation, fertilization, and embryonic development; and to evaluate factors that influence porcine preantral follicle growth in vitro. Preantral follicles isolated from prepubertal porcine ovaries were cultured for 4 days in the presence of different concentrations of porcine serum and FSH, and with different numbers of follicles per well. A series of experiments showed that porcine antral follicles can be grown at a high frequency in vitro from healthy preantral follicles with intact theca when cultured in North Carolina State University 23 medium supplemented with 1.5 ng/ml FSH, 7.5% serum, and when cultured with three follicles per well. After 4 days of culture, 68% healthy cumulus-enclosed oocytes from these follicles were obtained, and 51% of the oocytes completed meiotic maturation to the metaphase II stage. Fifty-three percent of the mature oocytes underwent fertilization, 43% of the fertilized oocytes cleaved, and 13% developed to the blastocyst stage. The results show 1) that porcine preantral follicles can grow efficiently to the antral stage using these culture conditions, and 2) that oocytes from in vitro-matured porcine preantral follicles can acquire meiotic competence and undergo fertilization and embryonic development.

The purpose of this study was to determine the rates of maturation, fertilization and embryo development of ultrarapidly frozen immature oocytes (immature cumulus-oocyte complexes; COCs) obtained from antral follicles in ovaries of patients with chocolate ovarian cysts. The COCs were cryopreserved by a vitrification method using 5.5 mol ethylene glycol l (-1) plus 1.0 mol sucrose l (-1) in Dulbecco's PBS (DPBS). The survival, maturation and fertilization rates, and the percentage of embryos developing to the two-cell stage were 59, 64, 70 and 71%, respectively. No significant differences were noted in the rates of maturation, fertilization and embryo development between control and cryopreserved oocytes. Two embryos that developed from cryopreserved oocytes of the oocyte donor programme were selected for transfer into the uterus of a recipient with premature ovarian failure, after the recipient had received steroid replacement. A biochemical pregnancy occurred in the recipient after embryo transfer. These results indicate that immature oocytes can survive after cryopreservation and subsequently can be cultured to mature oocytes that are capable of undergoing fertilization in vitro and developing into embryos.

OBJECTIVE:To study the morphological changes of apoptotic oocytes, and rates of in vitro maturation and apoptosis of human oocytes in relation to age.DESIGN:Prospective comparative study.SETTING:Reproductive medicine center.PATIENT(S):Women undergoing surgery for ovarian cysts.INTERVENTION(S):Oocytes were incubated in Ham's F-10 medium with 15% fetal cord serum (FCS) for 32 to 120 hours and were examined under inverted microscope every 6 to 8 hours.MAIN OUTCOME MEASURE(S):Oocyte maturation and apoptosis, Fas antigen.RESULT(S):The morphologic changes characteristic of apoptosis oocytes were shrinkage, or the occurrence of cytoplasmic condensation, membrane blebbing, fragmentation of the oocyte into "apoptotic" bodies of unequal size, or internucleosomal DNA cleavage as shown by TUNEL. The maturation rates of oocytes were highest in those from women aged 21 to 30 years, and lowest in those aged 41 to 50 years. Apoptosis occurred in 17.1% (age group 21 to 30 years), 37. 7% (31 to 40 years), and 52.3% (41 to 50 years). The rate of apoptosis of human immature oocytes cultured in vitro was significantly higher in those from older women who were 41 to 50 years old than in those women 21 to 40 years old. Fas antigen was found to be present on apoptotic oocyte membranes.CONCLUSION(S):The developmental potential of oocytes from older women decreased in vitro in a manner similar to that seen in vivo. DNA fragmentation in oocytes associated with apoptotic death might be one of the reasons for poor oocyte quality and lower fertility in older women. Fas antigen in the oocyte presumably mediates apoptosis.

This study aimed to investigate the development of human preantral follicles and oocyte maturation in vitro. Preantral follicles were obtained from follicular aspirates during egg retrieval carried out during an in-vitro fertilization (IVF) programme. They were first incubated in Ham's F10 medium with 15% fetal cord serum (FCS). After 28 days, the medium was supplemented with different doses of human menopausal gonadotrophin (HMG), human follicular fluid (hFF) and epidermal growth factor (EGF) by orthogonal design. Promotion of final maturation was completed in the presence of HMG and hFF. Development from preantral to antral follicles was found within 6-12 days of culture. With time, the proportion of follicles with diameters of >300 microm increased at 21-28 days of culture (P < 0.005). The maximum number of oocytes extruded, and first polar body formation, occurred in the presence of 0.15 IU/ml HMG 40% (v/v) hFF and 6 ng/ml EGF. We conclude that follicular aspirates obtained during egg retrieval in an IVF programme contain many preantral follicles which could develop into antral follicles with extrusion of oocytes in culture, and that the oocytes can mature in vitro. Hence, a new source of human oocytes is available.

OBJECTIVETo study oocyte maturation of human fetal preantral follicles in vitro, the effects of different factors on oocyte maturation.METHODSPreantral follicles were obtained from fetal ovaries from termination of 20-28 weeks gestation. Factors involved in the development, maturation of fetal preantral follicles were studied in tissue and cell culture by means of Northern blot, and RT-PCR (nested).RESULTS(1) Preantral follicles obtained from fetal ovary increased in size to more than 120 microns in diameter without antrum formation and with increasing time the preantral oocytes became mature with extrusion of 1st polar body, insulin-like growth factor 1 (IGF-1) had a more marked effect on oocyte maturation, as compared with epidermal growth factor (EGF). (2) Expression of alpha fetoprotein mRNA occurred in fetal follicles on day 5, 15, 25, 35 of culture, and became negative on day 45 of culture. (3) Medium consisted of 1. human menopasual gonadotropin (hMG), 2. follicular fluid, 3. IGF-1, 4. EGF increased the expression of bcl-2 mRNA by 17.6%, 22.4%, 47.1% and 37.5% respectively in fetal follicular cells, and down-regulated the expression of p53 mRNA by 19.8%, 22.1%, 42.6% and 31.6% respectively.CONCLUSIONS(1) The development and maturation of fetal preantral follicles in vitro differed from those in vivo. (2) Expression of bcl-2 mRNA increased and expression of wild-type p53 mRNA decreased during follicular development and maturation.