Novel inactivating mutations in the FSH receptor cause premature ovarian insufficiency with resistant ovary syndrome.

RESEARCH QUESTION: What is the genetic aetiology of three resistant ovary syndrome (ROS) pedigrees from 13 Chinese Han families with non-syndromic premature ovarian insufficiency (POI). DESIGN: The proband in each family was subjected to whole-exome sequencing. Bioinformatic and in-vitro functional analyses were performed for the functional characterization of the FSHR mutations. RESULTS: Four novel mutations, two homozygous mutations (c.419delA, c.1510C>T), and a compound heterozygous mutation (c.44G>A and deletion of exons 1 and 2) of FSHR were identified in the three non-syndromic POI-with-ROS families. Bioinformatic analysis predicted that the three novel point mutations in FSHR are deleterious and associated with POI in the three families, which was confirmed by in-vitro functional analysis, in which FSH-induced adenosine 3',5'-cyclic monophosphate production was abolished for all receptors. CONCLUSIONS: The three novel point mutations in FSHR were all functional inactivating mutations, and were the genetic aetiology of the three non-syndromic POI-with-ROS families. The first FSHR frameshift mutation is reported here, and the first missense mutation in the signal peptide-encoding region of FSHR to be associated with POI. Women affected by ROS should consider undergoing mutation screening for FSHR.

Spatial and temporal evaluations of estrogenic activity in tap water served by a water plant in Wuhan, China.

This study aimed to evaluate the spatial and temporal characteristics of estrogenic activities in tap water served by a water plant in Wuhan, China. Tap water samples were monthly collected from the three sampling sites with different distances of distribution network from the plant during April 2010-March 2011: Min (less than 0.1km), Mid (approximately 4km) and Max (approximately 8km). Estrogenic activities of solid phase-extracted tap waters were measured by using recombinant yeast assay incorporated with and without exogenous metabolic activation system (rat liver S9 fractions) and expressed as 17ß-estradiol equivalents (EEQ). Pro-estrogenic and estrogenic activity in tap water ranged from 151.4 to 1395.6pg EEQ/L and 35.2 to 1511pg EEQ/L, respectively. Average pro-estrogenic activity (680.3pg EEQ/L) was significantly higher than estrogenic activity (412.8pg EEQ/L) throughout the whole year. The pro-estrogenic activity significantly increased with the extending of distribution network, and was also statistically correlated with water temperature and pH. However, pro-estrogenic and estrogenic activity was not altered across four seasons. Our results suggest that the pro-estrogenic and estrogenic chemicals are present in tap water served by the water plant.

Shortened duration and reduced area of frozen soil in the Northern Hemisphere.

The changes in near-surface soil freeze-thaw cycles (FTCs) are crucial to understanding the related hydrological and biological processes in terrestrial ecosystems under a changing climate. However, long-term dynamics of soil FTCs at the hemisphere scale and the underlying mechanisms are not well understood. In this study, the spatiotemporal patterns and main driving factors of soil FTCs across the Northern Hemisphere (NH) during 1979-2017 were analyzed using multisource data fusion and attribution approaches. Our results showed that the duration and the annual mean area of frozen soil in the NH decreased significantly at rates of 0.13 ± 0.04 days/year and 4.9 × 104 km2/year, respectively, over the past 40 years. These were mainly because the date of frozen soil onset was significantly delayed by 0.1 ± 0.02 days/year, while the end of freezing and onset of thawing were substantially advanced by 0.21 ± 0.02 and 0.15 ± 0.03 days/year, respectively. Moreover, the interannual FTC changes were more drastic in Eurasia than in North America, especially at mid-latitudes (30°-45° N) and in Arctic regions (>75° N). More importantly, our results highlighted that near-surface air temperature (T a ) and snowpack are the main driving factors of the spatiotemporal variations in soil FTCs. Furthermore, our results suggested that the long-term dynamics of soil FTCs at the hemisphere scale should be considered in terrestrial biosphere models to reduce uncertainties in future simulations.

Evaluation of exposure to trihalomethanes in tap water and semen quality: a prospective study in Wuhan, China.

Trihalomethanes (THMs) have been demonstrated to adversely affect male reproductive health in animals, but the evidence in humans is limited. The study aimed to examine the association between THM exposure and semen quality in a Chinese population. We recruited 324 men from the same water supply district in Wuhan, China between April 2011 and May 2012. Exposure to THMs was evaluated based on their concentrations in tap water measured within 90 days preceding semen collection, the uptake factors of THMs and personal information on ingestion and showering/bathing. We found that TTHM [sum of chloroform (TCM) and brominated THMs (Br-THMs)], TCM and Br-THM uptakes via ingestion were associated with significant or suggestive decreasing trends in sperm concentration (P for trend=0.01, 0.03 and 0.05, respectively) and sperm count (P for trend=0.02, 0.05 and 0.09, respectively). Our results suggest that THM exposure via ingestion may adversely affect semen quality.

Drinking-water disinfection by-products and semen quality: a cross-sectional study in China.

BACKGROUND: Exposure to disinfection by-products (DBPs) has been demonstrated to impair male reproductive health in animals, but human evidence is limited and inconsistent. OBJECTIVE: We examined the association between exposure to drinking-water DBPs and semen quality in a Chinese population. METHODS: We recruited 2,009 men seeking semen analysis from the Reproductive Center of Tongji Hospital in Wuhan, China, between April 2011 and May 2012. Each man provided a semen sample and a urine sample. Semen samples were analyzed for sperm concentration, sperm motility, and sperm count. As a biomarker of exposure to drinking-water DBPs, trichloroacetic acid (TCAA) was measured in the urine samples. RESULTS: The mean (median) urinary TCAA concentration was 9.58 (7.97) µg/L (interquartile range, 6.01-10.96 µg/L). Compared with men with urine TCAA in the lowest quartile, increased adjusted odds ratios (ORs) were estimated for below-reference sperm concentration in men with TCAA in the second and fourth quartiles (OR = 1.79; 95% CI: 1.19, 2.69 and OR = 1.51; 95% CI: 0.98, 2.31, respectively), for below-reference sperm motility in men with TCAA in the second and third quartiles (OR = 1.46; 95% CI: 1.12, 1.90 and OR = 1.30; 95% CI: 1.00, 1.70, respectively), and for below-reference sperm count in men with TCAA in the second quartile (OR 1.62; 95% CI: 1.04, 2.55). Nonmonotonic associations with TCAA quartiles were also estimated for semen parameters modeled as continuous outcomes, although significant negative associations were estimated for all quartiles above the reference level for sperm motility. CONCLUSION: Our findings suggest that exposure to drinking-water DBPs may contribute to decreased semen quality in humans.