RANKL regulates male reproductive function

Infertile men have few treatment options. Here, we demonstrate that the transmembrane receptor activator of NF-kB ligand (RANKL) signaling system is active in mouse and human testis. RANKL is highly expressed in Sertoli cells and signals through RANK, expressed in most germ cells, whereas the RANKL-inhibitor osteoprotegerin (OPG) is expressed in germ and peritubular cells. OPG treatment increases wild-type mouse sperm counts, and mice with global or Sertoli-specific genetic suppression of Rankl have increased male fertility and sperm counts. Moreover, RANKL levels in seminal fluid are high and distinguishes normal from infertile men with higher specificity than total sperm count. In infertile men, one dose of Denosumab decreases RANKL seminal fluid concentration and increases serum Inhibin-B and anti-Mullerian-hormone levels, but semen quality only in a subgroup. This translational study suggests that RANKL is a regulator of male reproductive function, however, predictive biomarkers for treatment-outcome requires further investigation in placebo-controlled studies. There are few treatments for male infertility. Here, the authors show that the receptor activator of NF-kappa B ligand (RANKL) signalling pathway has important functions in sperm production and maturation, improves fertility in male mice and shows potential as a male infertility target.</p

Temporal Trends in Fertility Rates:A Nationwide Registry Based Study from 1901 to 2014

Increasing age at first childbirth has been suggested to increase the risk for infertility. Our objective is to determine whether women above thirty years of age historically have been able to sustain fertility rates above replacement level.A descriptive nationwide Danish study using birth registries from 1901-2014.Information on women's age at childbirth was obtained by using records from primary, secondary and tertiary institutions.Mothers to 8,024,969 live births.Mothers were stratified according to age at childbirth to determine total and age specific fertility rates.Total fertility rate (TFR) decreased from 4.1 to 1.8 children per woman and age specific fertility also decreased from 1901 to 2014. Women aged 30-34, 35-39 or 40-44 years in the first decade of the 20th century had higher fertility rates than the corresponding five year younger age groups (25-29, 30-34 and 35-39, respectively) have had for the last 65 years. On average, women gave birth to two children after the age of 30 and one or more child after 35 years of age in the beginning of the 1900s. Furthermore, women more than 40 years of age accounted for 10% of TFR in 1901 compared with 4% in 2014 despite usage of assisted reproduction.This nationwide study shows that women above 30 years of age historically have been able to sustain fertility rates above replacement level. This implies that other factors besides age are strong determinants of fertility in women above 30 years of age