Graphical Abstract Highlights d Crossover number is correlated across chromosomes within individual meiotic nuclei d CO covariation results from covariation of chromosome axis lengths within nuclei d CO covariation increases the frequencies of gametes with either many or few COs d Hyper-and hypo-CO gametes aid adaptation in a sporadically fluctuating environment SUMMARY Crossing over is a nearly universal feature of sexual reproduction. Here, analysis of crossover numbers on a per-chromosome and per-nucleus basis reveals a fundamental, evolutionarily conserved feature of meiosis: within individual nuclei, crossover frequencies covary across different chromosomes. This effect results from per-nucleus covariation of chromosome axis lengths. Crossovers can promote evolutionary adaptation. However, the benefit of creating favorable new allelic combinations must outweigh the cost of disrupting existing favorable combinations. Covariation concomitantly increases the frequencies of gametes with especially high, or especially low, numbers of crossovers, and thus might concomitantly enhance the benefits of crossing over while reducing its costs. A four-locus population genetic model suggests that such an effect can pertain in situations where the environment fluctuates: hyper-crossover gametes are advantageous when the environment changes while hypo-crossover gametes are advantageous in periods of environmental stasis. These findings reveal a new feature of the basic meiotic program and suggest a possible adaptive advantage.

Acephalic spermatozoa syndrome is a severe teratozoospermia that leads to male infertility. Our previous work showed that biallelic SUN5 mutations are responsible for acephalic spermatozoa syndrome in about half of affected individuals, while pathogenic mechanisms in the other individuals remain to be elucidated. Here, we identified a homozygous nonsense mutation in the testis-specific gene PMFBP1 using whole-exome sequencing in a consanguineous family with two infertile brothers with acephalic spermatozoa syndrome. Sanger sequencing of PMFBP1 in ten additional infertile men with acephalic spermatozoa syndrome and without SUN5 mutations revealed two homozygous variants and one compound heterozygous variant. The disruption of Pmfbp1 in male mice led to infertility due to the production of acephalic spermatozoa and the disruption of PMFBP1's cooperation with SUN5 and SPATA6, which plays a role in connecting sperm head to the tail. PMFBP1 mutation-associated male infertility could be successfully overcome by intracytoplasmic sperm injection (ICSI) in both mouse and human. Thus, mutations in PMFBP1 are an important cause of infertility in men with acephalic spermatozoa syndrome.

Water scarcity has become a global issue of severe concern. Great efforts have been undertaken to develop low-cost and highly efficient condensation strategies to relieve water shortages in arid regions. However, the rationale for design of an ideal condensing surface remains lacking due to the conflicting requirements for water nucleation and transport. In this work, we demonstrate that a biphilic nanoscale topography created by a scalable surface engineering method can achieve an ultraefficient water harvesting performance. With hydrophilic nanobumps on top of a superhydrophobic substrate, this biphilic topography combines the merits of biological surfaces with distinct wetting features (e.g., fogbasking beetles and water-repellent lotus), which enables a tunable water nucleation phenomenon, in contrast to the random condensation mode on their counterparts. By adjusting the contrasting wetting features, the characteristic water nucleation spacing can be tuned to balance the nucleation enhancement and water transport to cope with various environments. Guided by our nucleation density model, we show an optimal biphilic topography by tuning the nanoscale hydrophilic structure density, which allows an ∼349% water collection rate and ∼184% heat transfer coefficient as compared to the state-of-the-art superhydrophobic surface in a moisture-lacking atmosphere, offering a very promising strategy for improving the efficiency of water harvesting in drought areas.

Spermiogenesis is a complex and highly ordered spermatid differentiation process that requires reorganization of cellular structures. We have previously found that Atg7 is required for acrosome biogenesis. Here, we show that autophagy regulates the round and elongating spermatids. Specifically, we found that Atg7 is required for spermatozoa flagella biogenesis and cytoplasm removal during spermiogenesis. Spermatozoa motility of atg7-null mice dropped significantly with some extra-cytoplasm retained on the mature sperm head. These defects are associated with an impairment of the cytoskeleton organization. Functional screening revealed that the negative cytoskeleton organization regulator, PDLIM1 (PDZ and LIM domain 1 [elfin]), needs to be degraded by the autophagy-lysosome-dependent pathway to facilitate the proper organization of the cytoskeleton. Our results thus provide a novel mechanism showing that autophagy regulates cytoskeleton organization mainly via degradation of PDLIM1 to facilitate the differentiation of spermatids.

SUN (Sad1 and UNC84 domain containing)-domain proteins are reported to reside on the nuclear membrane playing distinct roles in nuclear dynamics. SUN5 is a new member of the SUN family, with little knowledge regarding its function. Here, we generated Sun5−/− mice and found that male mice were infertile. Most Sun5-null spermatozoa displayed a globozoospermia-like phenotype but they were actually acephalic spermatozoa. Additional studies revealed that SUN5 was located in the neck of the spermatozoa, anchoring sperm head to the tail, and without functional SUN5 the sperm head to tail coupling apparatus was detached from nucleus during spermatid elongation. Finally, we found that healthy heterozygous offspring could be obtained via intracytoplasmic injection of Sun5-mutated sperm heads for both male mice and patients. Our studies reveal the essential role of SUN5 in anchoring sperm head to the tail and provide a promising way to treat this kind of acephalic spermatozoa-associated male infertility.

High levels of autophagy exist in Leydig cells of the testis, but its physiological function is unknown. Gao et al. now show that autophagy promotes uptake of cholesterol, an essential precursor for testosterone synthesis, by removing the NHERF2 negative regulator of the high-density lipoprotein receptor SR-BI.

The ectoplasmic specialization (ES) is essential for Sertoli-germ cell communication to support all phases of germ cell development and maturity. Its formation and remodeling requires rapid reorganization of the cytoskeleton. However, the molecular mechanism underlying the regulation of ES assembly is still largely unknown. Here, we show that Sertoli cell-specific disruption of autophagy influenced male mouse fertility due to the resulting disorganized seminiferous tubules and spermatozoa with malformed heads. In autophagy-deficient mouse testes, cytoskeleton structures were disordered and ES assembly was disrupted. The disorganization of the cytoskeleton structures might be caused by the accumulation of a negative cytoskeleton organization regulator, PDLIM1, and these defects could be partially rescued by Pdlim1 knockdown in autophagy-deficient Sertoli cells. Altogether, our works reveal that the degradation of PDLIM1 by autophagy in Sertoli cells is important for the proper assembly of the ES, and these findings define a novel role for autophagy in Sertoli cell-germ cell communication.

Meiotic recombination is essential for fertility in most sexually reproducing species, but the molecular mechanisms underlying this process remain poorly understood in mammals. Here, we show that RNF20-mediated H2B ubiquitination is required for meiotic recombination. A germ cell-specific knockout of the H2B ubiquitination E3 ligase RNF20 results in complete male infertility. The Stra8-Rnf20−/− spermatocytes arrest at the pachytene stage because of impaired programmed double-strand break (DSB) repair. Further investigations reveal that the depletion of RNF20 in the germ cells affects chromatin relaxation, thus preventing programmed DSB repair factors from being recruited to proper positions on the chromatin. The gametogenetic defects of the H2B ubiquitination deficient cells could be partially rescued by forced chromatin relaxation. Taken together, our results demonstrate that RNF20/Bre1p-mediated H2B ubiquitination regulates meiotic recombination by promoting chromatin relaxation, and suggest an old drug may provide a new way to treat some oligo- or azoospermia patients with chromatin relaxation disorders.