Cutting-Edge Evaluation of Male Infertility

Pathak, Ujval Ishu; Gabrielsen, J. Scott; Lipshultz, Larry I.

doi:10.1016/j.ucl.2019.12.001

Cited by 32 publications

(15 citation statements)

References 53 publications

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“…Infertility affects about 15% of the global population, and approximately half of the cases are attributed to a "male factor" [1,2]. In male infertility, sperm dysfunction is considered as the most principal cause [3].…”

Section: Introductionmentioning

confidence: 99%

A novel mouse line with epididymal initial segment-specific expression of Cre recombinase driven by the endogenous Lcn9 promoter

et al. 2021

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Spermatozoa released from testes undergo a maturation process and acquire the capacity to fertilize ova through epididymal transit. The epididymis is divided into four regions, each with unique morphology, gene profile, luminal microenvironment and distinct function. To study the functions of relevant genes in the epididymal initial segment (IS), a novel IS-specific mouse model, Lcn9-Cre knock-in (KI) mouse line was generated via CRISPR/Cas9 technology. The TAG stop codon was replaced by a 2A-NLS-Cre cassette, resulting in the co-expression of Lcn9 and Cre recombinase. IS-specific Cre expression was first observed from postnatal day 17. Using the Rosa26tdTomato reporter mice, the Cre-mediated DNA recombination was detected exclusively in principal cells. The epididymal IS-specific Cre activity in vivo was further confirmed using Lcn9-Cre mice crossed with a mouse strain carrying Tsc1 floxed alleles (Tsc1flox/+). Cre expression did not affect either normal development or male fecundity. Different from any epididymis-specific Cre mice reported previously, the novel Lcn9-Cre mouse line can be used to introduce entire IS-specific conditional gene editing for gene functional study.

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Section: Introductionmentioning

confidence: 99%

A novel mouse line with epididymal initial segment-specific expression of Cre recombinase driven by the endogenous Lcn9 promoter

et al. 2021

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“…However, these non-systemic methods offer many advantages, including having fewer where biomarkers for predicting fertility are the subject of continuing research, with the goal of improving pregnancy outcomes. 86,87 Our preliminary studies support the use of the HBA as a surrogate biomarker for vaginal contraceptive activity of PPCM and other vaginal contraceptives acting by preventing sperm binding to the ovum. The HBA is selective of mature, viable spermatozoa capable of fertilization.…”

Section: Discussionmentioning

confidence: 57%

Evaluation of the novel vaginal contraceptive agent PPCM in preclinical studies using sperm hyaluronan binding and acrosome status assays

et al. 2021

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Background: Polyphenylene carboxymethylene (PPCM) sodium salt is a promising multipurpose technology for prevention of both sexually transmitted infections (STIs) and pregnancy. In preclinical studies, PPCM has demonstrated significant (1) antimicrobial activity against several important viral and bacterial pathogens and (2) contraceptive activity associated with premature acrosome loss.Objective: To further evaluate a vaginal antimicrobial compound as a contraceptive agent in preclinical studies utilizing a repurposed hyaluronan binding assay (HBA). Materials and methods:Semen samples containing either neat semen or washed spermatozoa were treated with increasing concentrations of PPCM or calcium ionophore A23187 (positive control). Sperm inactivation was measured by two methods: (1) double acrosome staining (AS), and (2) a hyaluronan binding assay (HBA ® ). Percentage of inactivated sperm was compared between untreated control sperm and those treated with PPCM or A23187.Results: PPCM had a significant (p < 0.05) and dose-dependent effect on sperm inactivation in both assays, with HBA detecting a higher proportion of inactivated sperm than AS. PPCM did not affect sperm motility and exhibited equivalent responses in the neat and washed samples.Discussion: Both HBA and AS confirmed that spermatozoa were rapidly inactivated at PPCM concentrations likely present in the vagina under actual use conditions and in a time-frame comparable to in vivo migration of spermatozoa out of seminal plasma into cervical mucus. Conclusion: PPCM vaginal gel may provide contraceptive protection as well as helpwith STI prevention. HBA may be a sensitive and much needed biomarker for sperm activity in future contraceptive development.

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“…It is also pooled in the literature that couples with a female partner of normal BMI and obese male partner are more susceptible to have prolonged time to conceive compared with couples with male partners of normal weight. Studies also bring on forth that couples with an obese male partner seeking Assisted reproductive technology (ART) have decreased pregnancy rates and increased pregnancy lost mainly because of prevalent DNA fragmentation [31].…”

Section: Obesitymentioning

confidence: 99%

Understanding Male Infertility for Promising ART

Zargar¹,

A²,

Lateef³

et al. 2021

Infertility and Assisted Reproduction

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Infertility is a serious problem of not being able to conceive despite regular intercourse for more than a year. Natural conception is seen to be achieved in 80%–85% of couples. About 15% of couples suffer infertility with male factor contributing to almost 50% of cases. Paradoxically, on traditional assessment, the underlying etiology of male contribution towards infertility remains unrecognized in 30% of the patients and thereby grouped as idiopathic. Diagnostics of male infertility cannot therefore be limited to usual semen analysis only. The spectrum of the recent research encourages the experts in the field to approach the Clinical, Molecular and cytogenetic shades associated with the problem besides secondary factors like life style and environment. Clinical assessment sums the medical history and physical examination of the affected individual. Molecular and cytogenetic analysis help gain new insights in understanding the problem and thereby an advantage for a successful assisted reproductive treatment (ART). Given the cost and burden ART puts in and prior to application of any invasive techniques, understanding precisely the etiology associated with male infertility is essential for the fertility specialist to circumvent inefficient or any unproductive steps in the fertilization process besides helping in counseling patients on their chance of success with the use of reproductive technology.

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Cutting-Edge Evaluation of Male Infertility

Cited by 32 publications

References 53 publications

A novel mouse line with epididymal initial segment-specific expression of Cre recombinase driven by the endogenous Lcn9 promoter

A novel mouse line with epididymal initial segment-specific expression of Cre recombinase driven by the endogenous Lcn9 promoter

Evaluation of the novel vaginal contraceptive agent PPCM in preclinical studies using sperm hyaluronan binding and acrosome status assays

Understanding Male Infertility for Promising ART

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