Value Analysis of Sperm Spontaneous Acrosome Reaction in Male Fertility Evaluation

A number of sperm proteins are involved in the processes from gamete adhesion to fusion, but the underlying mechanism is still unclear. Here, we established a mouse mutant, the EQUATORIN-knockout (EQTN-KO, Eqtn − / − ) mouse model and found that the EQTN-KO males have reduced fertility and sperm–egg adhesion, while the EQTN-KO females are fertile. Eqtn − / − sperm were normal in morphology and motility. Eqtn − / − -Tg (Acr-Egfp) sperm, which were produced as the acrosome reporter by crossing Eqtn − / − with Eqtn +/+ -Tg(Acr-Egfp) mice, traveled to the oviduct ampulla and penetrated the egg zona pellucida of WT females. However, Eqtn − / − males mated with WT females showed significant reduction in both fertility and the number of sperm attached to the zona-free oocyte. Sperm IZUMO1 and egg CD9 behaved normally in Eqtn − / − sperm when they were fertilized with WT egg. Another acrosomal protein, SPESP1, behaved aberrantly in Eqtn − / − sperm during the acrosome reaction. The fertility impairment of EQTN/SPESP1-double KO males lacking Eqtn and Spesp1 (Eqtn/Spesp1 − / − ) was more severe compared with that of Eqtn − / − males. Eqtn − / − -Tg (Eqtn) males, which were generated to rescue Eqtn − / − males, restored the reduced fertility.

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The impact of di-2-ethylhexyl phthalate on sperm fertility

10.1101/2020.04.09.034835 ◽

2020 ◽

Author(s):

Liliya Gabelev Khasin ◽

John Della Rosa ◽

Natalie Petersen ◽

Jacob Moeller ◽

Lance J. Kriegsfeld ◽

...

Keyword(s):

Bisphenol A ◽

Male Fertility ◽

Chronic Exposure ◽

Acrosome Reaction ◽

Endocrine Disrupting Chemicals ◽

Reproductive Potential ◽

Significant Risk ◽

Acute Effects ◽

The Impact ◽

Ethylhexyl Phthalate

AbstractA growing number of studies point to reduced fertility upon chronic exposure to endocrine-disrupting chemicals (EDCs) such as phthalates and plasticizers. These toxins are ubiquitous and are often found in food and beverage containers, medical devices, as well as in common household and personal care items. Animal studies with EDCs, such as phthalates and bisphenol A have shown a dose-dependent decrease in fertility and embryo toxicity upon chronic exposure. However, limited research has been conducted on the acute effects of these EDCs on male fertility. Here we used a murine model to test the acute effects of four ubiquitous environmental toxins: bisphenol A (BPA), di-2-ethylhexyl phthalate (DEHP), diethyl phthalate (DEP), and dimethyl phthalate (DMP) on sperm fertilizing ability and pre-implantation embryo development. The most potent of these toxins, di-2-ethylhexyl phthalate (DEHP), was further evaluated for its effect on sperm ion channel activity, capacitation status, acrosome reaction and generation of reactive oxygen species (ROS). DEHP demonstrated a profound hazardous effect on sperm fertility by producing an altered capacitation profile, impairing the acrosome reaction, and, interestingly, also increasing ROS production. These results indicate that in addition to its known chronic impact on reproductive potential, DEHP also imposes acute and profound damage to spermatozoa, and thus, represents a significant risk to male fertility.

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Ferritin Overload Suppresses Male Fertility Via altered Acrosome Reaction

Reproductive & Developmental Biology ◽

10.12749/rdb.2015.39.4.117 ◽

2015 ◽

Vol 39 (4) ◽

pp. 117-125

Author(s):

Woo-Sung Kwon ◽

Md Saidur Rahman ◽

Ye-Ji Kim ◽

Do-Yeol Ryu ◽

Amena Kahtun ◽

...

Keyword(s):

Male Fertility ◽

Acrosome Reaction

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Sperm gamma-aminobutyric acid type A receptor delta subunit (GABRD) and its interaction with purinergic P2X2 receptors in progesterone-induced acrosome reaction and male fertility

Reproduction Fertility and Development ◽

10.1071/rd16294 ◽

2017 ◽

Vol 29 (10) ◽

pp. 2060

Author(s):

Wenming Xu ◽

Ke Wang ◽

Yan Chen ◽

Xiao Tong Liang ◽

Mei Kuen Yu ◽

...

Keyword(s):

Male Fertility ◽

Acrosome Reaction ◽

Neck Region ◽

Type A ◽

Aminobutyric Acid ◽

Gamma Aminobutyric Acid ◽

Inhibitory Peptide ◽

P2x2 Receptor ◽

Acid Type ◽

Delta Subunit

The mechanism underlying the non-genomic action of progesterone in sperm functions and related Ca2+ mobilisation remains elusive. Herein we report the expression of gamma-aminobutyric acid type A receptor delta subunit (GABRD) in human and rodent sperm and its involvement in mediating the progesterone-induced acrosome reaction. GABRD was localised in the sperm head/neck region. A δ(392–422)-specific inhibitory peptide against GABRD blocked the progesterone-induced acrosome reaction and the associated increase in intracellular Ca2+. Similarly, an inhibitory effect against both progesterone-induced Ca2+ influx and the acrosome reaction was observed with a P2X2 receptor antagonist. The lack of synergism between the GABRD and P2X2 inhibitors suggests that these two receptors are playing a role in the same pathway. Furthermore, a co-immunoprecipitation experiment demonstrated that GABRD could undergo protein–protein interactions with the Ca2+-conducting P2X2 receptor. This interaction between the receptors could be reduced following progesterone (10 μM) inducement. Significantly reduced GABRD expression was observed in spermatozoa from infertile patients with reduced acrosome reaction capacity, suggesting that normal expression of GABRD is critical for the sperm acrosome reaction and thus male fertility. The results of the present study indicate that GABRD represents a novel progesterone receptor or modulator in spermatozoa that is responsible for the progesterone-induced Ca2+ influx required for the acrosome reaction through its interaction with the P2X2 receptor.

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Sperm Lipid Markers of Male Fertility in Mammals

International Journal of Molecular Sciences ◽

10.3390/ijms22168767 ◽

2021 ◽

Vol 22 (16) ◽

pp. 8767

Author(s):

Shuwen Shan ◽

Fangzheng Xu ◽

Marc Hirschfeld ◽

Bertram Brenig

Keyword(s):

Plasma Membrane ◽

Lipid Metabolism ◽

Male Fertility ◽

Acrosome Reaction ◽

Membrane Lipids ◽

Reproductive Function ◽

Cellular Processes ◽

Male Reproductive Function ◽

Sperm Plasma Membrane ◽

Mammalian Spermatozoa

Sperm plasma membrane lipids are essential for the function and integrity of mammalian spermatozoa. Various lipid types are involved in each key step within the fertilization process in their own yet coordinated way. The balance between lipid metabolism is tightly regulated to ensure physiological cellular processes, especially referring to crucial steps such as sperm motility, capacitation, acrosome reaction or fusion. At the same time, it has been shown that male reproductive function depends on the homeostasis of sperm lipids. Here, we review the effects of phospholipid, neutral lipid and glycolipid homeostasis on sperm fertilization function and male fertility in mammals.

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Sperm membrane proteins DCST1 and DCST2 are required for the sperm-egg fusion process in mice and fish

10.1101/2021.04.18.440256 ◽

2021 ◽

Author(s):

Taichi Noda ◽

Andreas Blaha ◽

Yoshitaka Fujihara ◽

Krista R. Gert ◽

Chihiro Emori ◽

...

Keyword(s):

Membrane Proteins ◽

Male Sterility ◽

Crucial Role ◽

Male Fertility ◽

Acrosome Reaction ◽

Vertebrate Species ◽

Essential Factor ◽

C Elegans ◽

Sperm Membrane ◽

Single Knockout

AbstractThe process of sperm-egg fusion is critical for successful fertilization, yet the underpinning mechanisms that regulate these steps have remained unclear in vertebrates. Here, we show that both mouse and zebrafish DCST1 and DCST2 are necessary in sperm to fertilize the egg, similar to their orthologs SPE-42 and SPE-49 in C. elegans and Sneaky in D. melanogaster. Mouse Dcst1 and Dcst2 single knockout (KO) spermatozoa are able to undergo the acrosome reaction and show normal relocalization of IZUMO1, an essential factor for sperm-egg fusion, to the equatorial segment. While both single KO spermatozoa can bind to the oolemma, they rarely fuse with oocytes, resulting in male sterility. Similar to mice, zebrafish dcst1 KO males are subfertile and dcst2 and dcst1/2 double KO males are sterile. Zebrafish dcst1/2 KO spermatozoa are motile and can approach the egg, but rarely bind to the oolemma. These data demonstrate that DCST1/2 are essential for male fertility in two vertebrate species highlighting their crucial role as conserved factors in fertilization.

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Acute Myeloid Leukemia Affects Mouse Sperm Parameters, Spontaneous Acrosome Reaction, and Fertility Capacity

International Journal of Molecular Sciences ◽

10.3390/ijms20010219 ◽

2019 ◽

Vol 20 (1) ◽

pp. 219 ◽

Cited By ~ 3

Author(s):

Yulia Michailov ◽

Eitan Lunenfeld ◽

Joseph Kapilushnik ◽

Shevach Friedler ◽

Eckart Meese ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Male Fertility ◽

Myeloid Leukemia ◽

Acrosome Reaction ◽

Sperm Quality ◽

Sperm Concentration ◽

Reproductive Age ◽

Sperm Parameters ◽

Chemotherapy Treatment ◽

Acute Myeloid

Leukemia is one of the most common cancers in patients of reproductive age. It is well known that chemotherapy, used as anti-cancer therapy, adversely affects male fertility. Moreover, the negative effect of leukemia on sperm quality, even before chemotherapy treatment, has been reported. However, the mechanisms behind this disease’s effect on sperm quality remains unknown. In this study, we examine the direct effect of leukemia and chemotherapy alone and in combination on sperm parameters and male fertility. For this, we developed an acute myeloid leukemia (AML) mouse model (mice were treated with AML cells C1498 and developed leukemia); these mice then received cytarabine chemotherapy. Our findings reveal a significant reduction in sperm concentration and motility and a significant increase in abnormal morphology and spontaneous acrosome reaction of the sperm following AML and chemotherapy treatment, alone and in combination. We also found a reduction in male fertility and the number of delivered offspring. Our results support previous findings that AML impairs sperm parameters and show for the first time that AML increases spontaneous acrosome reaction and decreases male fertility capacity and number of offspring.

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