Author Correction: Loss-of-function mutations in QRICH2 cause male infertility with multiple morphological abnormalities of the sperm flagella.

In the original version of this Article, the Acknowledgements section omitted the National Key Research and Development Program of China (SQ2018YFC1003603).

Exposure of Hyperandrogen During Pregnancy Causes Depression- and Anxiety-Like Behaviors, and Reduced Hippocampal Neurogenesis in Rat Offspring.

The hippocampus is a region in which neurogenesis persists and retains substantial plasticity throughout lifespan. Accumulating evidences indicate an important role of androgens and androgenic signaling in the regulation of offspring hippocampal neurogenesis and the survival of mature or immature neurons and gliocyte. Hyperandrogenic disorders have been associated with depression and anxiety. Previous studies have found that pregnant hyperandrogenism may increase the susceptibility of the offspring to depression or anxiety and lead to abnormal hippocampal neurogenesis in rats. In this study, pregnant rats were given subcutaneous injection of aromatase inhibitor letrozole in order to establish a maternal hyperandrogenic environment for the fetal rats. The lithium chloride (LICl) was used as an intervention agent since a previous study has shown that lithium chloride could promote neurogenesis in the hippocampus. The results revealed that pregnant administration of letrozole resulted in depressive- and anxious-like behaviors in the adolescent period. A remarkable decrease in immature nerve cells marked by doublecortin and mature neurons co-expressed by Brdu and NeuN in adult years were detected in the hippocampal dentate gyrus of adolescent rats. Lithium chloride alleviated the effects on neurobehavioral and promoted the differentiation and proliferation of neural progenitor cells, while a hyperandrogenic intrauterine environment had no effects on astrocytes marked by GFAP in the dentate gyrus. Furthermore, the Wnt/ß-catenin signaling pathway related to normal development of hippocampus was examined but there was no significant changes in Wnt signaling pathway members. Our study provides evidence that exposure of androgen during pregnancy leads to alterations in depressive, anxious and stereotypical behaviors and these phenotypes are possibly associated with changes in neurogenesis in the dentate gyrus.

Loss-of-function mutations in QRICH2 cause male infertility with multiple morphological abnormalities of the sperm flagella.

Aberrant sperm flagella impair sperm motility and cause male infertility, yet the genes which have been identified in multiple morphological abnormalities of the flagella (MMAF) can only explain the pathogenic mechanisms of MMAF in a small number of cases. Here, we identify and functionally characterize homozygous loss-of-function mutations of QRICH2 in two infertile males with MMAF from two consanguineous families. Remarkably, Qrich2 knock-out (KO) male mice constructed by CRISPR-Cas9 technology present MMAF phenotypes and sterility. To elucidate the mechanisms of Qrich2 functioning in sperm flagellar formation, we perform proteomic analysis on the testes of KO and wild-type mice. Furthermore, in vitro experiments indicate that QRICH2 is involved in sperm flagellar development through stabilizing and enhancing the expression of proteins related to flagellar development. Our findings strongly suggest that the genetic mutations of human QRICH2 can lead to male infertility with MMAF and that QRICH2 is essential for sperm flagellar formation.