Light-mediated activation reveals a key role for protein kinase A and sarcoma protein kinase in the development of sperm hyper-activated motility

Shahar, Shiran; Wiser, Amir; Ickowicz, Debbi; Lubart, Rachel; Shulman, Adrian; Breitbart, Haim

doi:10.1093/humrep/der232

Cited by 64 publications

(53 citation statements)

References 50 publications

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“…Thus, it is not unreasonable to conclude that ART intervention during the periconception period might induce a health risk in the resulting offspring. During ART, specifically in vitro gamete manipulation and embryo system, spermatozoa, oocytes, and embryos are exposed to various nonphysiological factors, such as culture media, altered pH [51], light [52,53], higher oxygen pressure [54], increased concentration of reproductive hormones [55], and mechanical injection or biopsy, all of which contribute to an altered periconception environment [56]. In addition to in vitro ART, a sub-optimal uterine environment following embryo transfer is thought to further influence the long-term viability of offspring.…”

Section: Discussionmentioning

confidence: 99%

Alteration in the expression of the renin-angiotensin system in the myocardium of mice conceived by in vitro fertilization†

Wang

Zhang

Fang

et al. 2018

Biology of Reproduction

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Epidemiological studies have revealed that offspring conceived by in vitro fertilization (IVF) have an elevated risk of cardiovascular malformations at birth, and are more predisposed to cardiovascular diseases. The renin-angiotensin system (RAS) plays an essential role in both the pathogenesis of congenital heart disease in fetuses and cardiovascular dysfunction in adults. This study aimed to assess the relative expression levels of genes in the RAS pathway in mice conceived using IVF, compared to natural mating with superovulation. Results demonstrated that expression of the angiotensin II receptor type 1 (AGTR1), connective tissue growth factor (CTGF), and collagen 3 (COL3), in the myocardial tissue of IVF-conceived mice, was elevated at 3 weeks, 10 weeks, and 1.5 years of age, when compared to their non-IVF counterparts. These data were supported by microRNA microarray analysis of the myocardial tissue of aged IVF-conceived mice, where miR-100, miR-297, and miR-758, which interact with COL3, AGTR1, and COL1 respectively, were upregulated when compared to naturally mated mice of the same age. Interestingly, bisulfite sequencing data indicated that IVF-conceived mice exhibited decreased methylation of CpG sites in Col1. In support of our in vivo investigations, miR-297 overexpression was shown to upregulate AGTR1 and CTGF, Effects of in vitro fertilization on myocardium, 2018, Vol. 99, No. 6 1277 and increased cell proliferation in cultured H9c2 cardiomyocytes. These findings indicate that the altered expression of RAS in myocardial tissue might contribute to cardiovascular malformation and/or dysfunction in IVF-conceived offspring. Furthermore, these cardiovascular abnormalities might be the result of altered DNA methylation and abnormal regulation of microRNAs. Summary SentenceAltered expression of the renin-angiotensin system in myocardial tissue might contribute to an increased risk of cardiovascular malformations and dysfunction in IVF offspring, and is involved in abnormal regulations of DNA methylation and microRNAs.

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Section: Discussionmentioning

confidence: 99%

Alteration in the expression of the renin-angiotensin system in the myocardium of mice conceived by in vitro fertilization†

Wang

Zhang

Fang

et al. 2018

Biology of Reproduction

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“…We recently showed that PKA mediates light-induced hyperactivated motility (HAM) in human sperm. 49 It is currently accepted that capacitated sperm represents HAM. During the capacitation process, sperm change their motility pattern from progressive to HAM.…”

Section: Protein Kinases a And Cmentioning

confidence: 99%

Mechanism of sperm capacitation and the acrosome reaction: role of protein kinases

Ickowicz¹,

Finkelstein²,

Breitbart³

2012

Asian J Androl

203

130

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Mammalian sperm must undergo a series of biochemical and physiological modifications, collectively called capacitation, in the female reproductive tract prior to the acrosome reaction (AR). The mechanisms of these modifications are not well characterized though protein kinases were shown to be involved in the regulation of intracellular Ca 21 during both capacitation and the AR. In the present review, we summarize some of the signaling events that are involved in capacitation. During the capacitation process, phosphatidyl-inositol-3-kinase (PI3K) is phosphorylated/activated via a protein kinase A (PKA)-dependent cascade, and downregulated by protein kinase C a (PKCa). PKCa is active at the beginning of capacitation, resulting in PI3K inactivation. During capacitation, PKCa as well as PP1c2 is degraded by a PKA-dependent mechanism, allowing the activation of PI3K. The activation of PKA during capacitation depends mainly on cyclic adenosine monophosphate (cAMP) produced by the bicarbonate-dependent soluble adenylyl cyclase. This activation of PKA leads to an increase in actin polymerization, an essential process for the development of hyperactivated motility, which is necessary for successful fertilization. Actin polymerization is mediated by PIP 2 in two ways: first, PIP 2 acts as a cofactor for phospholipase D (PLD) activation, and second, as a molecule that binds and inhibits actin-severing proteins such as gelsolin. Tyrosine phosphorylation of gelsolin during capacitation by Src family kinase (SFK) is also important for its inactivation. Prior to the AR, gelsolin is released from PIP 2 and undergoes dephosphorylation/activation, resulting in fast F-actin depolymerization, leading to the AR.

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“…Photobiostimulation occurs when the light is absorbed by porphyrins, flavins or cytochromes and absorbed energy is transferred to oxygen molecules leading to generation of reactive oxygen species (ROS) [53]. ROS are responsible for mediating the effects of light [13].…”

Section: Possible Mechanisms Of Laser Action On Spermatozoamentioning

confidence: 99%

Laser irradiation effects and its possible mechanisms of action on spermatozoa functions in domestic animals

Lone¹,

Mohanty²,

Kumaresan³

et al. 2017

APJR

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Light-mediated activation reveals a key role for protein kinase A and sarcoma protein kinase in the development of sperm hyper-activated motility

Abstract: Light irradiation of human sperm for a short time causes a significant increase in HAM in a mechanism mediated by ROS production, activation of PKA, Src and Ca²⁺ influx.

Cited by 64 publications

References 50 publications

Alteration in the expression of the renin-angiotensin system in the myocardium of mice conceived by in vitro fertilization†

Alteration in the expression of the renin-angiotensin system in the myocardium of mice conceived by in vitro fertilization†

Mechanism of sperm capacitation and the acrosome reaction: role of protein kinases

Laser irradiation effects and its possible mechanisms of action on spermatozoa functions in domestic animals

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