Disruption of mitochondrial unfolded protein response results in telomere shortening in mouse oocytes and somatic cells.

Caseinolytic peptidase P (CLPP) plays a central role in mitochondrial unfolded protein response (mtUPR) by promoting the breakdown of misfolded proteins and setting in motion a cascade of reactions to re-establish protein homeostasis. Global germline deletion of Clpp in mice results in female infertility and accelerated follicular depletion. Telomeres are tandem repeats of 5'-TTAGGG-3' sequences found at the ends of the chromosomes. Telomeres are essential for maintaining chromosome stability during somatic cell division and their shortening is associated with cellular senescence and aging. In this study, we asked whether the infertility and ovarian aging phenotype caused by global germline deletion of Clpp is associated with somatic aging, and tested telomere length in tissues of young and aging mice. We found that impaired mtUPR caused by the lack of CLPP is associated with accelerated telomere shortening in both oocytes and somatic cells of aging mice. In addition, expression of several genes that maintain telomere integrity was decreased, and double-strand DNA breaks were increased in telomeric regions. Our results highlight how impaired mtUPR can affect telomere integrity and demonstrate a link between loss of mitochondrial protein hemostasis, infertility, and somatic aging.

Miscarriage determination in first trimester based on alpha-fetoprotein extracted from sanitary pads.

OBJECTIVE: To determine if high alpha-fetoprotein (AFP) level in vaginal blood collected on a sanitary pad can assist with detecting an active miscarriage. DESIGN: A prospective cohort study. SETTING: Academic medical center. PATIENT(S): Five groups were evaluated: women with active miscarriage, pregnancy of unknown location, completed miscarriage or extrauterine pregnancy (EUP), ongoing pregnancy, and undergoing elective dilation and curettage (D&C). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): For each patient, AFP level in the vaginal blood collected on a sanitary pad was quantified. RESULT(S): The vaginal blood AFP median levels (and their ranges) were 3.7 IU/mL (0.5-739.2) and 4,542 IU/mL (15.6-100,000) in the active miscarriage (n = 16) and the elective D&C (n = 24) groups, respectively. Alpha-fetoprotein was detected in all elective D&C and active miscarriage cases except in 1 case. In the ongoing pregnancy group (n = 35), only 2 of 35 specimens showed detectable AFP levels. In the pregnancy of unknown location (n = 12) and the completed miscarriage or EUP (n = 10) groups, no AFP was detected. Receiver operating characteristic analysis demonstrated 93.7% sensitivity and 97.8% specificity for the detection of an active miscarriage (cutoff 0.61 IU/mL; area under the curve 0.96). CONCLUSION(S): Alpha-fetoprotein can be extracted from vaginal blood collected on sanitary pads. A high level of vaginal AFP can assist with the same-day detection of an active miscarriage. This novel test is useful in differentiating active miscarriages from ongoing pregnancies, completed miscarriages, and EUPs and, therefore, it reduces uncertainty, anxiety level, and number of repeat office visits.

Short-Term Outcomes of Vaginal Hysterectomy at the Time of Robotic Sacrocolpopexy.

OBJECTIVE: With the introduction of robotic sacrocolpopexy (RSC) at our institution in 2008, we noted a reduction in residents' vaginal hysterectomy (VH) experience. In 2012, we made a transition to perform VH on all robotic sacrocolpopexies. Our objective was to report our short-term outcomes and adverse events. METHODS: In this case series, we evaluated women who underwent VH with concomitant RSC for stages II to IV pelvic organ prolapse between 2012 and 2017. In these cases, the vesicovaginal and rectovaginal spaces were developed transvaginally. Descriptive analysis including demographics, short-term outcomes, and adverse events are reported. RESULTS: In this group of 209 women, median (interquartile interval) duration of follow-up was 49 (26-60) weeks. The majority of the women were white (84.7%) and postmenopausal (80.9%), with a mean (SD) age of 59 (9) years. At a median follow-up time of 49 weeks, pelvic organ prolapse quantification revealed 20 patients (12.4%) with Ba or Bp greater or equal to 0 and 1.4% of patients required repeat prolapse surgery. Among 9 women (4.3%) with postoperative fever, 4 (1.9%) were treated for pelvic collection/abscess. Of 5 women (2.4%) who had venous thromboembolism, 3 (1.4%) were diagnosed with pulmonary embolism. There were 18 patients (8.6%) treated for urinary tract infection within 6 postoperative weeks. Mesh exposure was noted in 16 (7.7%) of the patients, and 11 (6.2%) required reoperation. CONCLUSIONS: Vaginal hysterectomy at the time of RSC may increase the risk of infection and mesh exposure compared with procedures without concomitant hysterectomy.

Mitochondrial Stress Response Gene Clpp Is Not Required for Granulosa Cell Function.

Mitochondrial unfolded protein response (UPRmt) is a highly conserved mechanism, which is activated upon cellular or metabolic stress and aims to help cells maintain homeostasis. CLPP (caseinolytic peptidase P) plays a crucial factor for UPRmt; it promotes the degradation of unfolded mitochondrial proteins. Global germline deletion of Clpp in mice results in female infertility and accelerated follicular depletion. Here, we asked whether CLPP is necessary for granulosa/cumulus cell function. Clppflox/flox mice were generated and crossbred with Cyp19a1-Cre mice to generate mice with granulosa/cumulus cell-specific Clpp deletion (Clpp-/-). Mature (8-week-old) Clpp-/- female mice (8-week-old) were compared to same age wild type (WT) mice. We found that mature Clpp-/- female mice were fertile and produced a similar number of pups per litter compared to WT. Folliculogenesis was not affected by the loss of CLPP in granulosa/cumulus cells as Clpp-/- and WT mice had a similar number of primordial, primary, secondary, early antral, and antral follicles. The number of germinal vesicles (GV) and MII oocytes collected from Clpp-/- and WT female mice were also similar. Our findings demonstrate that fertility in female mice is not affected by granulosa/cumulus cell-specific UPRmt disruption through CLPP deletion.

Child health, parasites and lower socioeconomic status: Outcomes of a long-term screening, intervention and training study by health volunteers in rural Nepal.

BACKGROUND: Nepal is a developing country with limited resources for health provision due to its geographic difficulties and frequent natural disasters, such as floods and earthquakes. Children are at risk of growth retardation due to inadequate food intake and unhealthy environment. Lower back pain is common among the adults and causes limitations in daily activities. MATERIAL/METHODS: A group of voluntary Turkish medical students, doctors and civil members conducted a field study, together with Nepalese doctors (MDs) and local volunteers, concerned with health-screening, intervention practices and on-site training in rural Nepal between 2013 and 2015. Physical examination of participants, together with stool examinations for parasites were done and those for whom treatment was indicated were referred to MDs who also ran a field pharmacy containing donated medications. RESULTS: Totally, 1148 individuals-725 children and 423 adults-were screened between 2013 and 2015. Musculoskeletal problems and upper respiratory tract infections were primary complaints among adults and sick children, respectively. Three-quarters of 203 collected stools had ≥ 1 parasite(s). CONCLUSIONS: Growth retardation in children observed during the study, the burden of intestinal parasites on Nepalese children and unavailability of effective health services for citizens in rural areas should direct local authorities to allocate greater resources for country's health infrastructure improvement and to provide a higher standard of childhood nutrition.