A novel CCDC112-dependent process of sperm midpiece formation and epididymal maturation.

The sperm mitochondrial sheath has proposed functions in structural support and energy production for motility. Here we define coiled coil domain containing protein 112, CCDC112, as crucial for male fertility, specifically in the assembly and function of the mitochondrial sheath. We unveiled a previously unrecognised process of epididymal mitochondrial sheath maturation.

AXDND1 is required to balance spermatogonial commitment and for sperm tail formation in mice and humans.

Dynein complexes are large, multi-unit assemblies involved in many biological processes via their critical roles in protein transport and axoneme motility. Using next-generation sequencing of infertile men presenting with low or no sperm in their ejaculates, we identified damaging variants in the dynein-related gene AXDND1. We thus hypothesised that AXDND1 is a critical regulator of male fertility.

Genetic mutation of results in male infertility due to abnormal sperm tail composition.

The transition zone is a specialised gate at the base of cilia/flagella, which separates the ciliary compartment from the cytoplasm and strictly regulates protein entry. We identified a potential new regulator of the male germ cell transition zone, CEP76. We demonstrated that CEP76 was involved in the selective entry and incorporation of key proteins required for sperm function and fertility into the ciliary compartment and ultimately the sperm tail.

Recent advances in reproductive research in Australia and New Zealand: highlights from the Annual Meeting of the Society for Reproductive Biology, 2022.

In 2022, the Society for Reproductive Biology came together in Christchurch New Zealand (NZ), for its first face-to-face meeting since the global COVID-19 pandemic. The meeting showcased recent advancements in reproductive research across a diverse range of themes relevant to human health and fertility, exotic species conservation, and agricultural breeding practices. Here, we highlight the key advances presented across the main themes of the meeting, including advances in addressing opportunities and challenges in reproductive health related to First Nations people in Australia and NZ; increasing conservation success of exotic species, including ethical management of invasive species; improvements in our understanding of developmental biology, specifically seminal fluid signalling, ovarian development and effects of environmental impacts such as endocrine-disrupting chemicals; and leveraging scientific breakthroughs in reproductive engineering to drive solutions for fertility, including in assisted reproductive technologies in humans and agricultural industries, and for regenerative medicine.

AXDND1 is required to balance spermatogonial commitment and for sperm tail formation in mice and humans.

Dynein complexes are large, multi-unit assemblies involved in many biological processes including male fertility via their critical roles in protein transport and axoneme motility. Previously we identified a pathogenic variant in the dynein gene in an infertile man. Subsequently we identified an additional four potentially compound heterozygous variants of unknown significance in in two additional infertile men.

The katanin A-subunits KATNA1 and KATNAL1 act co-operatively in mammalian meiosis and spermiogenesis to achieve male fertility.

Katanins, a class of microtubule-severing enzymes, are potent M-phase regulators in oocytes and somatic cells. How the complex and evolutionarily crucial, male mammalian meiotic spindle is sculpted remains unknown. Here, using multiple single and double gene knockout mice, we reveal that the canonical katanin A-subunit KATNA1 and its close paralogue KATNAL1 together execute multiple aspects of meiosis.

has dual roles in the limiting of meiotic crossovers and germ cell maintenance in mammals.

Meiotic crossovers are required for accurate chromosome segregation and producing new allelic combinations. Meiotic crossover numbers are tightly regulated within a narrow range, despite an excess of initiating DNA double-strand breaks. Here, we reveal the tumor suppressor FANCM as a meiotic anti-crossover factor in mammals.

Spastin is an essential regulator of male meiosis, acrosome formation, manchette structure and nuclear integrity.

The development and function of male gametes is dependent on a dynamic microtubule network, yet how this is regulated remains poorly understood. We have recently shown that microtubule severing, via the action of the meiotic AAA ATPase protein clade, plays a crucial role in this process. Here, we sought to elucidate the roles of spastin, an as-yet-unexplored member of this clade in spermatogenesis.

Reproductive biology research down under: highlights from the Australian and New Zealand Annual Meeting of the Society for Reproductive Biology, 2021.

Against the backdrop of a global pandemic, the Society for Reproductive Biology (SRB) 2021 meeting reunited the Australian and New Zealand reproductive research community for the first time since 2019 and was the first virtual SRB meeting. Despite the recent global research disruptions, the conference revealed significant advancements in reproductive research, the importance of which span human health, agriculture, and conservation. A core theme was novel technologies, including the use of medical microrobots for therapeutic and sperm delivery, diagnostic hyperspectral imaging, and hydrogel condoms with potential beyond contraception.

KATNB1 is a master regulator of multiple katanin enzymes in male meiosis and haploid germ cell development.

Katanin microtubule-severing enzymes are crucial executers of microtubule regulation. Here, we have created an allelic loss-of-function series of the katanin regulatory B-subunit KATNB1 in mice. We reveal that KATNB1 is the master regulator of all katanin enzymatic A-subunits during mammalian spermatogenesis, wherein it is required to maintain katanin A-subunit abundance.

Delta and epsilon tubulin in mammalian development.

Delta (δ-) and epsilon (ε-) tubulin are lesser-known cousins of alpha (α-) and beta (β-) tubulin. They are likely to regulate centriole function in a broad range of species; however, their in vivo role and mechanism of action in mammals remain mysterious. In unicellular species and mammalian cell lines, mutations in δ- and ε-tubulin cause centriole destabilization and atypical mitosis and, in the most severe cases, cell death.

Haploid male germ cells-the Grand Central Station of protein transport.

Background: The precise movement of proteins and vesicles is an essential ability for all eukaryotic cells. Nowhere is this more evident than during the remarkable transformation that occurs in spermiogenesis-the transformation of haploid round spermatids into sperm. These transformations are critically dependent upon both the microtubule and the actin cytoskeleton, and defects in these processes are thought to underpin a significant percentage of human male infertility.

The Microtubule Severing Protein Katanin Regulates Proliferation of Neuronal Progenitors in Embryonic and Adult Neurogenesis.

Microtubule severing regulates cytoskeletal rearrangement underlying various cellular functions. Katanin, a heterodimer, consisting of catalytic (p60) and regulatory (p80) subunits severs dynamic microtubules to modulate several stages of cell division. The role of p60 katanin in the mammalian brain with respect to embryonic and adult neurogenesis is poorly understood.

An optimised STAPUT method for the purification of mouse spermatocyte and spermatid populations.

The purification of individual male germ cell populations is integral for the molecular and biochemical characterisation of specific spermatogenic phases. Although a number of more contemporary techniques have been developed, velocity sedimentation using the STAPUT method remains as a gold standard for this purpose. The gentle nature of the technique, wherein germ cell subpopulations are separated by sedimentation at unit gravity, results in the isolation of viable and high-purity cells.

Fifty years of reproductive biology in Australia: highlights from the 50th Annual Meeting of the Society for Reproductive Biology (SRB).

The 2018 edition of the Society for Reproductive Biology's (SRB) Annual Meeting was a celebration of 50 years of Australian research into reproductive biology. The past 50 years has seen many important contributions to this field, and these advances have led to changes in practice and policy, improvements in the efficiency of animal reproduction and improved health outcomes. This conference review delivers a dedicated summary of the symposia, discussing emerging concepts, raising new questions and proposing directions forward.

The cytoskeleton in spermatogenesis.

As germ cells progress through spermatogenesis, they undergo a dramatic transformation, wherein a single, diploid spermatogonial stem cell ultimately produces thousands of highly specialised, haploid spermatozoa. The cytoskeleton is an integral aspect of all eukaryotic cells. It concomitantly provides both structural support and functional pliability, performing key roles in many fundamental processes including, motility, intracellular trafficking, differentiation and cell division.

Evidence that fertility trades off with early offspring fitness as males age.

Models of ageing predict that sperm function and fertility should decline with age as sperm are exposed to free radical damage and mutation accumulation. However, theory also suggests that mating with older males should be beneficial for females because survival to old age is a demonstration of a male's high genetic and/or phenotypic quality. Consequently, declines in sperm fitness may be offset by indirect fitness benefits exhibited in offspring.

Katanin-like 2 (KATNAL2) functions in multiple aspects of haploid male germ cell development in the mouse.

The katanin microtubule-severing proteins are essential regulators of microtubule dynamics in a diverse range of species. Here we have defined critical roles for the poorly characterised katanin protein KATNAL2 in multiple aspects of spermatogenesis: the initiation of sperm tail growth from the basal body, sperm head shaping via the manchette, acrosome attachment, and ultimately sperm release. We present data suggesting that depending on context, KATNAL2 can partner with the regulatory protein KATNB1 or act autonomously.

Introducing a Fresh Cadaver Model for Ultrasound-guided Central Venous Access Training in Undergraduate Medical Education.

Introduction: Over the past decade, medical students have witnessed a decline in the opportunities to perform technical skills during their clinical years. Ultrasound-guided central venous access (USG-CVA) is a critical procedure commonly performed by emergency medicine, anesthesia, and general surgery residents, often during their first month of residency. However, the acquisition of skills required to safely perform this procedure is often deficient upon graduation from medical school.

Consistent age-dependent declines in human semen quality: a systematic review and meta-analysis.

Reduced fertility typically occurs among women in their late 30s, but increasing evidence indicates that advanced paternal age is associated with changes in reproduction as well. Numerous studies have investigated age-based declines in semen traits, but the impact of paternal age on semen parameter values remains inconclusive. Using data from 90 studies (93,839 subjects), we conducted a systematic review and meta-analysis to quantify the effect of male age on seven ejaculate traits (semen volume, sperm concentration, total sperm count, morphology, total motility, progressive motility and DNA fragmentation).

Becoming a leader in patient satisfaction: changing the culture of care in an academic community hospital.

In the context of the current health care payer system, quality of care standards, financial incentives and consumer choice are not well aligned, yet competition for increased admissions has become a matter of survival. Satisfaction and loyalty are two constructs that are the most meaningful measures in the context of sustaining and increasing admissions. Lehigh Valley Hospital and Health Network (LVHHN) launched an ambitious patient satisfaction improvement initiative in 2001.

Longer term outcomes from a randomised trial of prescribing strategies in otitis media.

Background: There are limited data about the longer-term outcomes in acute otitis media (AOM) when comparing the realistic alternatives of immediate prescription of antibiotics and a 'wait and see' or delayed prescribing policy.

Aim: The aim was to assess the medium and longer term outcomes of two prescribing strategies for otitis media.

Design Of Study: Follow-up of a randomised controlled trial cohort.

Role for pituitary adenylate cyclase activating polypeptide in cystitis-induced plasticity of micturition reflexes.

Pituitary adenylate cyclase activating polypeptide (PACAP) peptides are expressed and regulated in sensory afferents of the micturition pathway. Although these studies have implicated PACAP in bladder control, the physiological significance of these observations has not been firmly established. To clarify these issues, the roles of PACAP and PACAP signaling in micturition and cystitis were examined in receptor characterization and physiological assays.