Epsilon tubulin is an essential determinant of microtubule-based structures in male germ cells.

Alpha, beta, and gamma tubulins are essential building blocks for all eukaryotic cells. The functions of the non-canonical tubulins, delta, epsilon, and zeta, however, remain poorly understood and their requirement in mammalian development untested. Herein we have used a spermatogenesis model to define epsilon tubulin (TUBE1) function in mice. We show that TUBE1 is essential for the function of multiple complex microtubule arrays, including the meiotic spindle, axoneme and manchette and in its absence, there is a dramatic loss of germ cells and male sterility. Moreover, we provide evidence for the interplay between TUBE1 and katanin-mediated microtubule severing, and for the sub-specialization of individual katanin paralogs in the regulation of specific microtubule arrays.

Genetic mutation of Cep76 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. In the mutant, sperm tails were shorter and immotile as a consequence of deficits in essential sperm motility proteins including DNAH2 and AKAP4, which accumulated at the sperm neck in the mutant. Severe annulus, fibrous sheath, and outer dense fibre abnormalities were also detected in sperm lacking CEP76. Finally, we identified that CEP76 dictates annulus positioning and structure. This study suggests CEP76 as a male germ cell transition zone protein and adds further evidence to the hypothesis that the spermatid transition zone and annulus are part of the same functional structure.

Exome-informed formulations of food proteins enhance body growth and feed conversion efficiency in ad libitum-fed mice.

Meeting requirements for dietary proteins, especially of essential amino acids (EAAs), is critical for the life-long health of living organisms. However, defining EAA targets for preparing biologically-matched nutrition that satisfies metabolic requirements for protein remains challenging. Previous research has shown the advantages of 'exome matching' in representing the specific requirement of dietary AAs, where the target dietary AA profile was derived from in silico translation of the genome of an organism, specifically responsible for protein expression (the 'exome'). However, past studies have assessed these effects in only one sex, for few parameters (body mass and composition), and have used purified diets in which protein is supplied as a mixture of individual AAs. Here, for the first time, we utilise a computational method to guide the formulation of custom protein blends and test if exome matching can be achieved at the intact protein level, through blending standard protein ingredients, ultimately leading to optimal growth, longevity and reproductive function. Mice were provided ad libitum (ad lib) access to one of the four iso-energetic protein-limited diets, two matched and two mis-matched to the mouse exome target, and fed at a fixed protein energy level of 6.2%. During or following 13-weeks of feeding, the food intake, body growth, composition and reproductive functions were measured. Compared to the two mis-matched diets, male and female animals on the exome-matched diet with protein digestibility correction applied, exhibited significantly improved growth rates and final body mass. The feed conversion efficiency in the same diet was also increased by 62% and 40% over the worst diets for males and females, respectively. Male, not female, exhibited higher accretion of lean body mass with the matched, digestibility-corrected diet. All reproductive function measures in both sexes were comparable among diets, with the exception of testicular daily sperm production in males, which was higher in the two matched diets versus the mis-matched diets. The results collectively demonstrate the pronounced advantages of exome-matching in supporting body growth and improving feed conversion efficiency in both sexes. However, the potential impact of this approach in enhancing fertility needs further investigation.

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 AXDND1 in an infertile man. Subsequently we identified an additional four potentially compound heterozygous variants of unknown significance in AXDND1 in two additional infertile men. We thus tested the role of AXDND1 in mammalian male fertility by generating a knockout mouse model. Axdnd1-/- males were sterile at all ages but could undergo one round of histologically complete spermatogenesis. Subsequently, a progressive imbalance of spermatogonial commitment to spermatogenesis over self-renewal occurred, ultimately leading to catastrophic germ cell loss, loss of blood-testis barrier patency and immune cell infiltration. Sperm produced during the first wave of spermatogenesis were immotile due to abnormal axoneme structure, including the presence of ectopic vesicles and abnormalities in outer dense fibres and microtubule doublet structures. Sperm output was additionally compromised by a severe spermiation defect and abnormal sperm individualisation. Collectively, our data highlight the essential roles of AXDND1 as a regulator of spermatogonial commitment to spermatogenesis and during the processes of spermiogenesis where it is essential for sperm tail development, release and motility.

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. We show KATNA1 and KATNAL1 collectively regulate the male meiotic spindle, cytokinesis and midbody abscission, in addition to diverse spermatid remodelling events, including Golgi organisation, and acrosome and manchette formation. We also define KATNAL1-specific roles in sperm flagellum development, manchette regulation and sperm-epithelial disengagement. Finally, using proteomic approaches, we define the KATNA1, KATNAL1 and KATNB1 mammalian testis interactome, which includes a network of cytoskeletal and vesicle trafficking proteins. Collectively, we reveal that the presence of multiple katanin A-subunit paralogs in mammalian spermatogenesis allows for 'customised cutting' via neofunctionalisation and protective buffering via gene redundancy.

Performance of comprehensive first trimester fetal anatomy assessment.

OBJECTIVE: Ultrasound assessment of the fetal anatomy and fetal echocardiography are feasible in the first trimester of pregnancy. This study was designed to assess the performance of a comprehensive fetal anatomy assessment in a high-risk population at a tertiary fetal medicine unit. METHODS: A retrospective review of high-risk patients undergoing comprehensive fetal anatomy ultrasound assessment between 11 weeks and 13 + 6 weeks of gestation was conducted. Findings of the early anatomy ultrasound scan were compared with those of the second trimester anatomy scan, and birth outcomes or post-mortem results. RESULTS: Early anatomy ultrasounds were performed in 765 patients. The sensitivity of the scan for detecting fetal anomalies compared to the birth outcome was 80.5% (95% CI 73.5-86.3) and specificity was 93.1% (95%CI 90.6-95.2). Positive and negative predictive values were 78.5% (95% CI 71.4-84.6) and 93.9% (95% CI 91.4-95.8), respectively. The most missed and overdiagnosed abnormalities were ventricular septal defects. The second trimester ultrasound had sensitivity of 69.0% (95% CI 55.5-80.5) and specificity of 87.5% (95% CI 84.3-90.2). CONCLUSIONS: In a high-risk population, early assessments had similar performance metrics as the second trimester anatomy ultrasound. We advocate for a comprehensive fetal assessment in the care of high-risk pregnancies.

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. Using a SpastKO/KO mouse model, we reveal that spastin loss resulted in a complete loss of functional germ cells. Spastin plays a crucial role in the assembly and function of the male meiotic spindle. Consistent with meiotic failure, round spermatid nuclei were enlarged, indicating aneuploidy, but were still able to enter spermiogenesis. During spermiogenesis, we observed extreme abnormalities in manchette structure, acrosome biogenesis and, commonly, a catastrophic loss of nuclear integrity. This work defines an essential role for spastin in regulating microtubule dynamics during spermatogenesis, and is of potential relevance to individuals carrying spastin variants and to the medically assisted reproductive technology industry.

DDB1- and CUL4-associated factor 12-like protein 1 (Dcaf12l1) is not essential for male fertility in mice.

Male infertility is a common condition affecting at least 7% of men worldwide and is often genetic in origin. Using whole exome sequencing, we recently discovered three hemizygous, likely damaging variants in DDB1- and CUL4-associated factor 12-like protein 1 (DCAF12L1) in men with azoospermia. DCAF12L1 is located on the X-chromosome and as identified by single cell sequencing studies, its expression is enriched in human testes and specifically in Sertoli cells and spermatogonia. However, very little is known about the role of DCAF12L1 in spermatogenesis, thus we generated a knockout mouse model to further explore the role of DCAF12L1 in male fertility. Knockout mice were generated using CRISPR/Cas9 technology to remove the entire coding region of Dcaf12l1 and were assessed for fertility over a broad range of ages (2-8 months of age). Despite outstanding genetic evidence in men, loss of DCAF12L1 had no discernible impact on male fertility in mice, as highlighted by breeding trials, histological assessment of the testis and epididymis, daily sperm production and evaluation of sperm motility using computer assisted methods. This disparity is likely due to the parallel evolution, and subsequent divergence, of DCAF12 family members in mice and men or the presence of compounding environmental factors in men.

Zinc finger RNA binding protein 2 (ZFR2) is not required for male fertility in the mouse.

BACKGROUND: Thousands of genes are expressed during spermatogenesis and male infertility has a strong genetic component. Within this study, we focus on the role of Zfr2 in male fertility, a gene previously implicated in human male fertility. To date, very little is known about the role of ZFR2 in either humans or mice. To this end, the requirement for ZFR2 in male fertility was assessed using a knockout mouse model. RESULTS: Zfr2 was found to be expressed in the testes of both humans and mice. Deletion of Zfr2 was achieved via removal of exon 2 using CRISPR-Cas9 methods. The absence of Zfr2 did not result in a reduction in any fertility parameters assessed. Knockout males were capable of fostering litter sizes equal to wild type males, and there were no effects of Zfr2 knockout on sperm number or motility. We note Zfr2 knockout females were also fertile. CONCLUSIONS: The absence of Zfr2 alone is not sufficient to cause a reduction in male fertility in mice.

The collaborative development through multidisciplinary and advocate consensus of an accessible notice of rights for people with intellectual disabilities in police custody.

Background People with intellectual disabilities are over-represented in the criminal justice system. The United Nations' Convention on the Rights of Persons with Disabilities (UNCRPD) enshrines a right to equal access to justice for persons with disabilities (Article 13, UNCRPD). Accessible information is a key aspect of exercising this right. Yet, many jurisdictions, including Ireland, are yet to develop accessible information for disabled people who may be arrested. Aims This paper describes the collaborative development through multidisciplinary and advocate consensus of an accessible (Easy -to- Read) Notice of Rights (ERNR) for people with intellectual disabilities in police custody in Ireland. Methods Guidelines developed by Ireland's representative organisation for people with intellectual disabilities and examples of international practice were used to develop a draft ERNR by the primary researcher in partnership with an expert from a representative organisation for people with intellectual disabilities. The ERNR was developed thereafter through two focus groups with a view to achieving consensus with a focus on accessibility, accuracy and layout. This included a multidisciplinary focus group with participants from a representative organisation for people with intellectual disabilities, psychology, speech and language therapy, the police force, public health, forensic psychiatry, mental health, law and, subsequently, a focus group of people with lived experience of intellectual disability. Results Progressive development of the ERNR resulted in incremental improvements in textual accuracy as well as the inclusion of more accessible language and imagery. Originality/value This is the first attempt at developing an easy-to-read document relating to the legal rights of suspects in police custody in Ireland and, accordingly, this procedural innovation promises to assist, not just persons with intellectual disabilities, but also those with limited literacy at the point of arrest. The methodology used in the preparation of the document, employing a focus group to achieve consensus with participation from both multiple disciplines and persons with an intellectual disability, is in harmony with the ethos of the UNCPRD. This methodology may usefully be employed by other member states that have ratified the Convention but have yet to develop accessible version of the legal rights and entitlements that extend to arrested persons under their domestic law.

Assessing the relationship between psychosocial risk and pregnancy outcomes using the perinatal integrated psychosocial assessment (PIPA) tool.

BACKGROUND: The Perinatal Integrated Psychosocial Assessment (PIPA) tool screens for anxiety, depression, and psychosocial factors in pregnancy. We aimed to assess the association between PIPA-determined psychosocial risk and obstetric and neonatal outcomes. METHODS: Cohort study of all pregnant women who gave birth at ≥20 weeks of gestation in 2017-2019 at a tertiary maternity hospital in, Sydney, Australia. Women completed PIPA at their first antenatal visit and were assigned a PIPA risk category. At-risk women were reviewed and referred for support. The association between PIPA risk category and obstetric and neonatal outcomes was evaluated using multivariable logistic regression adjusting for sociodemographic and pregnancy factors. RESULTS: In all, 5969 women completed PIPA; 71.4% were assessed no/low risk, 17.5% medium risk, and 11.1% medium-high/high risk. Compared with no/low-risk women, medium-high/high-risk women were more likely to remain in hospital for >72 hours (aOR 1.47 [95% CI 1.33-1.64]); to not be breastfeeding at discharge (aOR 1.77 [95% CI 1.20-2.61]); to have their infants experience birth complications (aOR 1.24 [95% CI 1.03-1.50]); and to be admitted to the NICU (aOR 1.63 [95% CI 1.26-2.11]). There was a modest increase in odds of cesarean birth (aOR 1.12 [95% CI 1.00-1.27]), and no association with preterm birth or low birthweight. The risk of adverse outcomes disappeared for medium-high/high-risk women referred for support. CONCLUSIONS: The PIPA tool identified one in 10 women at high psychosocial risk with increased risk of adverse obstetric and neonatal outcomes. Adverse outcomes were attenuated for high-risk women who were referred for extra support, suggesting that psychosocial review and referral for high-risk women may reduce the risk of adverse obstetric and neonatal outcomes.

Impact of role conflicts and self-efficacy on academic performance of graduate-entry healthcare students: A lagged study.

Graduate entry healthcare students experience many challenges during their academic journey. The impact of these challenges needs to be considered to support students through their training and education. In this study, we examined the impact of experiencing these role conflicts (at the outset of the academic year), for example, family and caring responsibilities, activities with family/friends, and daily tasks/chores, on the academic performance (at the end of the academic year) of graduate-entry healthcare students. We also investigated the potential of students' self-efficacy for learning to mitigate the extent to which such role conflicts impact academic performance. Findings demonstrate that the more graduate entry healthcare students experienced conflicts between their life responsibilities and their academic responsibilities, the worse their academic performance was across the year. This negative relationship was somewhat mitigated by high self-efficacy for learning. The practical implications of our research suggest the need to provide specific mitigation strategies to support healthcare students regarding conflicts between their life/family responsibilities and their academic work.

Human INHBB Gene Variant (c.1079T>C:p.Met360Thr) Alters Testis Germ Cell Content, but Does Not Impact Fertility in Mice.

Testicular-derived inhibin B (α/ß B dimers) acts in an endocrine manner to suppress pituitary production of follicle-stimulating hormone (FSH), by blocking the actions of activins (ß A/B/ß A/B dimers). Previously, we identified a homozygous genetic variant (c.1079T>C:p.Met360Thr) arising from uniparental disomy of chromosome 2 in the INHBB gene (ß B-subunit of inhibin B and activin B) in a man suffering from infertility (azoospermia). In this study, we aimed to test the causality of the p.Met360Thr variant in INHBB and testis function. Here, we used CRISPR/Cas9 technology to generate InhbbM364T/M364T mice, where mouse INHBB p.Met364 corresponds with human p.Met360. Surprisingly, we found that the testes of male InhbbM364T/M364T mutant mice were significantly larger compared with those of aged-matched wildtype littermates at 12 and 24 weeks of age. This was attributed to a significant increase in Sertoli cell and round spermatid number and, consequently, seminiferous tubule area in InhbbM364T/M364T males compared to wildtype males. Despite this testis phenotype, male InhbbM364T/M364T mutant mice retained normal fertility. Serum hormone analyses, however, indicated that the InhbbM364T variant resulted in reduced circulating levels of activin B but did not affect FSH production. We also examined the effect of this p.Met360Thr and an additional INHBB variant (c.314C>T: p.Thr105Met) found in another infertile man on inhibin B and activin B in vitro biosynthesis. We found that both INHBB variants resulted in a significant disruption to activin B in vitro biosynthesis. Together, this analysis supports that INHBB variants that limit activin B production have consequences for testis composition in males.

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. Our data shows that complete loss of KATNB1 from germ cells is incompatible with sperm production, and we reveal multiple new spermatogenesis functions for KATNB1, including essential roles in male meiosis, acrosome formation, sperm tail assembly, regulation of both the Sertoli and germ cell cytoskeletons during sperm nuclear remodelling, and maintenance of seminiferous epithelium integrity. Collectively, our findings reveal that katanins are able to differentially regulate almost all key microtubule-based structures during mammalian male germ cell development, through the complexing of one master controller, KATNB1, with a 'toolbox' of neofunctionalised katanin A-subunits.

A feedback journey: employing a constructivist approach to the development of feedback literacy among health professional learners.

BACKGROUND: Feedback, if effectively provided by the teacher and utilised by the learner, enables improvement in academic performance. It is clear from current literature that the provision of feedback by teachers is not sufficient on its own to guarantee improvements as early university entrants may not be sufficiently equipped to effectively engage with feedback. Nonetheless, it is critical for health professional students to develop feedback literacy early, in order to prepare them for a professional career of lifelong learning and critical thinking. The overarching aim of this study was to identify a feasible, sustainable approach to improve feedback literacy among students on pre-qualifying health professional programmes. METHODS: The study was divided into two phases. A mixed-methods approach grounded in constructivism was employed. Participants included teachers and learners from the School of Allied Health at X University, and two internationally acclaimed educationalists. In phase 1, first year students were encouraged to use an established online platform to upload modular feedback and develop personal learning action plans aimed at improving academic performance. A follow-up survey highlighted poor engagement with this method. Thus, the second phase focused on the co-construction of a suite of modules to develop these skills, supported by academic staff. Interviews were conducted with participants to review and refine this initiative. RESULTS: Learners' engagement with the first phase of the study was poor. Thus, the second phase provided all stakeholders with the opportunity to feed into the development of a suite of modules, designed to encourage teachers and learners to work in partnership to nurture these skills. All stakeholder groups reported short- and long-term benefits with this approach, but also highlighted challenges towards its implementation. CONCLUSION: The development of feedback literacy among health professional learners is essential. The transferability of such skills has been highlighted in the literature and by all stakeholder groups involved in this study. Finding a balance between introducing these skills at a time early enough to highlight their importance among university entrants is challenging. Further balance must be achieved between the workload required to achieve these skills and current programme demands for both teachers and learners.

HENMT1 is involved in the maintenance of normal female fertility in the mouse.

PIWI-interacting small RNAs (piRNAs) maintain genome stability in animal germ cells, with a predominant role in silencing transposable elements. Mutations in the piRNA pathway in the mouse uniformly lead to failed spermatogenesis and male sterility. By contrast, mutant females are fertile. In keeping with this paradigm, we previously reported male sterility and female fertility associated with loss of the enzyme HENMT1, which is responsible for stabilising piRNAs through the catalysation of 3'-terminal 2'-O-methylation. However, the Henmt1 mutant females were poor breeders, suggesting they could be subfertile. Therefore, we investigated oogenesis and female fertility in these mice in greater detail. Here, we show that mutant females indeed have a 3- to 4-fold reduction in follicle number and reduced litter sizes. In addition, meiosis-II mutant oocytes display various spindle abnormalities and have a dramatically altered transcriptome which includes a down-regulation of transcripts required for microtubule function. This down-regulation could explain the spindle defects observed with consequent reductions in litter size. We suggest these various effects on oogenesis could be exacerbated by asynapsis, an apparently universal feature of piRNA mutants of both sexes. Our findings reveal that loss of the piRNA pathway in females has significant functional consequences.

CRISPs Function to Boost Sperm Power Output and Motility.

Fertilization requires sperm to travel long distances through the complex environment of the female reproductive tract. Despite the strong association between poor motility and infertility, the kinetics of sperm tail movement and the role individual proteins play in this process is poorly understood. Here, we use a high spatiotemporal sperm imaging system and an analysis protocol to define the role of CRISPs in the mechanobiology of sperm function. Each of CRISP1, CRISP2, and CRISP4 is required to optimize sperm flagellum waveform. Each plays an autonomous role in defining beat frequency, flexibility, and power dissipation. We thus posit that the expansion of the CRISP family from one member in basal vertebrates, to three in most mammals, and four in numerous rodents, represents an example of neofunctionalization wherein proteins with a common core function, boosting power output, have evolved to optimize different aspects of sperm tail performance.

Challenges for people with intellectual disabilities in law enforcement interactions in Ireland; thematic analysis informed by 1537 person-years' experience.

BACKGROUND: People with intellectual disabilities (PWID) are over-represented in criminal justice systems globally. This over-representation reveals itself at once in the demographic make-up of prison populations, as well as those detained in police settings as suspects of crime. While it is well-established in international literature that individuals who find themselves in the latter scenario face particular challenges in negotiating the forensic formalities routinely followed by the police at the pre-trial stage of criminal proceedings on account of their impairments, the specific difficulties experienced by PWID as suspects within Ireland's criminal justice system has yet to be explained, or indeed, understood. In seeking to address this research lacuna, this paper yields an account of a qualitative study which was aimed at identifying the unique challenges which PWID face in their interactions with Law Enforcement Officials (LEOs) in Ireland. AIMS: This study aimed to elicit perspectives across a range of disciplines with regard to barriers for PWID interacting with LEOs in Ireland, and sought viewpoints on the content of a proposed awareness programme. METHODS: A survey using purposive sampling was used to elicit viewpoints from people from representative organisations for PWID, people working with voluntary organisations for PWID, healthcare professionals working with PWID and professionals from the criminal justice system (including members of An Garda Siochana, lawyers, members of the Irish judiciary and officials within the Airport Police). Data were anonymised at the point of collection. Qualitative thematic analysis was conducted to extract themes based on the data retrieved through the survey. RESULTS: Ninety-five (n = 95) responses were received from individuals reporting a cumulative experience of 1537 person-years. Respondents identified themselves as members of one of three groups; people working in a voluntary or representative organisation for PWID (n = 42, 44.2%); people working in healthcare (n = 31, 32.6%); and people working in law enforcement (n = 22, 23.1%). Three themes were identified from the qualitative thematic analysis. The first theme, "Barriers to Communication", identified challenges which PWID and LEO experience in their mutual interactions and communications with one another. The second theme, "Building Awareness and Skills", identified elements of an ID awareness programme for LEOs. The third theme, "Institutional and System Change", identified possible lines of innovation with respect to contemporary police practice and the availability of supports for both PWID and the LEOs who work with them. ORIGINALITY/VALUE: This study represents the first dedicated qualitative inquiry conducted on a multidisciplinary level into the barriers which healthcare professionals, legal professionals and disability advocacy groups perceive to be faced by PWID in their interactions with LEOs in Ireland. Consequently, the findings from this study will act as a valuable template in the direction of informing the development of an ID awareness programme for LEOs in Ireland. In addition, these research findings are expected to usefully inform the development of national policy and protocols in areas related to health, disability and justice. In offering a rich evidence-base for future policy initiatives, the timing of this study is particularly significant. The recent ratification by Ireland of the UN Convention for the Rights of People with Disabilities (UNCRPD), together with the synchronous emergence of an evolving emphasis on human rights-based policing at a national level in Ireland, has meant that Irish policymakers have a unique opportunity to re-imagine the pre-trial formalities of Ireland's criminal process in order to demonstrate an increased sensitivity to the needs of PWID. Securing equal access to justice for such individuals, it is important to emphasise, is a legal requirement pursuant to Article 13 of the UNCRPD. To the extent therefore that this study yields unique insights into the barriers faced by PWID in their interactions with LEOs, the results of this study are potentially generalisable to other jurisdictions that have ratified the UNCRPD and are developing policy to accord with Article 13.

The Sertoli cell expressed gene secernin-1 (Scrn1) is dispensable for male fertility in the mouse.

BACKGROUND: Male infertility is a prevalent clinical presentation for which there is likely a strong genetic component due to the thousands of genes required for spermatogenesis. Within this study we investigated the role of the gene Scrn1 in male fertility. Scrn1 is preferentially expressed in XY gonads during the period of sex determination and in adult Sertoli cells based on single cell RNA sequencing. We investigated the expression of Scrn1 in juvenile and adult tissues and generated a knockout mouse model to test its role in male fertility. RESULTS: Scrn1 was expressed at all ages examined in the post-natal testis; however, its expression peaked at postnatal days 7-14 and SCRN1 protein was clearly localized to Sertoli cells. Scrn1 deletion was achieved via removal of exon 3, and its loss had no effect on male fertility or sex determination. Knockout mice were capable of siring litters of equal size to wild type counterparts and generated equal numbers of sperm with comparable motility and morphology characteristics. CONCLUSIONS: Scrn1 was found to be dispensable for male fertility, but this study identifies SCRN1 as a novel marker of the Sertoli cell cytoplasm.