The molecular mechanisms mediating mammalian fertilization

Bhakta, Hanisha; Refai, Fares H.; Avella, Matteo A.

doi:10.1242/dev.176966

Cited by 43 publications

(43 citation statements)

References 139 publications

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“…These include acrosome formation which is a key event that is tightly controlled. The acrosome is an acidic membrane-bound organelle of Golgi- and endosomal/lysosomal-derived origin containing substances that facilitate fertilization [102,103]. Intriguingly, during spermiogenesis USP8 re-localizes together with the sperm-specific heat shock protein 40 (HSP40)/DNAJ chaperone protein Msj-1 and proteasomes to the cytoplasmic surface of the developing acrosome maintaining this particular co-localization in mature spermatozoa [104,105].…”

Section: The Role Of Usp8 In Sperm Acrosome Formationmentioning

confidence: 99%

Ubiquitin-specific protease 8 (USP8/UBPy): a prototypic multidomain deubiquitinating enzyme with pleiotropic functions

Dufner

Knobeloch

2019

Biochemical Society Transactions

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Protein modification by ubiquitin is one of the most versatile posttranslational regulations and counteracted by almost 100 deubiquitinating enzymes (DUBs). USP8 was originally identified as a growth regulated ubiquitin-specific protease and is like many other DUBs characterized by its multidomain architecture. Besides the catalytic domain, specific protein–protein interaction modules were characterized which contribute to USP8 substrate recruitment, regulation and targeting to distinct protein complexes. Studies in mice and humans impressively showed the physiological relevance and non-redundant function of USP8 within the context of the whole organism. USP8 knockout (KO) mice exhibit early embryonic lethality while induced deletion in adult animals rapidly causes lethal liver failure. Furthermore, T-cell specific ablation disturbs T-cell development and function resulting in fatal autoimmune inflammatory bowel disease. In human patients, somatic mutations in USP8 were identified as the underlying cause of adrenocorticotropic hormone (ACTH) releasing pituitary adenomas causing Cushing's disease (CD). Here we provide an overview of the versatile molecular, cellular and pathology associated function and regulation of USP8 which appears to depend on specific protein binding partners, substrates and the cellular context.

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Section: The Role Of Usp8 In Sperm Acrosome Formationmentioning

confidence: 99%

Ubiquitin-specific protease 8 (USP8/UBPy): a prototypic multidomain deubiquitinating enzyme with pleiotropic functions

Dufner

Knobeloch

2019

Biochemical Society Transactions

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“…The transport of lipophilic molecules is a requirement for sperm maturation during capacitation (21,22). Albumin takes up cholesterol shed from the sperm plasma membrane, allowing capacitation to proceed (21,23,24).…”

Section: Albumin Is Used In Culture Media For Ivf Intrauterine Insemmentioning

confidence: 99%

Phthalates in albumin from human serum: implications for assisted reproductive technology

et al. 2021

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Albumin, a vital protein in cell culture systems, is derived from whole blood or blood products. The culture of human gametes and developing embryos for assisted reproductive technology (ART) uses albumin of human origin. Human serum albumin (HSA) is derived from expired blood obtained from blood banks. This blood has been stored in polyvinyl chloride bags made clear and flexible with di-2ethylhexyl phthalate (DEHP). However, DEHP can leach from the bags into stored blood and cofractionate with HSA during albumin isolation. DEHP and its metabolite, mono-ethylhexyl phthalate, are known endocrine disruptors that are reported to have negative effects when directly supplemented in media for in vitro fertilization using gametes from a variety of animals. Therefore, the contamination of ART media with DEHP and mono-ethylhexyl phthalate through HSA supplementation may affect the outcomes of ART procedures. Although the embryology laboratory is strictly monitored to prevent a wide variety of contaminations, phthalate contamination of HSA has not been broadly examined. This review outlines the function of HSA in ART procedures and the production of HSA from whole blood. Finally, the review highlights the effects of acute phthalate exposures on gametes during in vitro procedures. Phthalates found in human serum albumin are present in media used for ART at levels that impair developmental endpoints in model species.

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“…Two key questions of fertilization studies in several model organisms are as follows: how does the sperm-egg interaction and fusion occur (for reviews: Ref. [24][25][26], and how does the fertilized egg initiate a transient elevation in intracellular calcium concentration (Ca 2+ transient) that is necessary for successful activation of embryonic development (for reviews: Ref. [27][28][29][30][31][32][33].…”

Section: Fertiliz Ati On and Ac Tivati On Of De Velopmentmentioning

confidence: 99%

Toward the understanding of biology of oocyte life cycle in Xenopus Laevis: No oocytes left behind

Sato

Tokmakov

2020

Reprod Medicine & Biology

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Background For the past more than 25 years, we have been focusing on the developmental and reproductive biology of the female gametes, oocytes, and eggs, of the African clawed frog Xenopus laevis. Methods The events associated with the life cycle of these cells can be classified into the four main categories: first, oogenesis and cell growth in the ovary during the first meiotic arrest; second, maturation and ovulation that occur simultaneously and result in the acquisition of fertilization competence and the second meiotic arrest; third, fertilization, that is sperm‐induced transition from egg to zygote; and fourth, egg death after spontaneous activation in the absence of fertilizing sperm. Main findings Our studies have demonstrated that signal transduction system involving tyrosine kinase Src and other oocyte/egg membrane‐associated molecules such as uroplakin III and some other cytoplasmic proteins such as mitogen‐activated protein kinase (MAPK) play important roles for successful ovulation, maturation, fertilization, and initiation of embryonic development. Conclusion We summarize recent advances in understanding cellular and molecular mechanisms underlying life cycle events of the oocytes and eggs. Our further intention is to discuss and predict potentially promising impact of the recent findings on the challenges facing reproductive biology and medicine, as well as societal contexts.

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The molecular mechanisms mediating mammalian fertilization

Cited by 43 publications

References 139 publications

Ubiquitin-specific protease 8 (USP8/UBPy): a prototypic multidomain deubiquitinating enzyme with pleiotropic functions

Ubiquitin-specific protease 8 (USP8/UBPy): a prototypic multidomain deubiquitinating enzyme with pleiotropic functions

Phthalates in albumin from human serum: implications for assisted reproductive technology

Toward the understanding of biology of oocyte life cycle in Xenopus Laevis: No oocytes left behind

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