Proteomic changes in uterine flushings after levonorgestrel treatment and effects on sperm function

Reproduction ◽  
2018 ◽  
Author(s):  
Gabriela Hernández-Silva ◽  
Marta Durand ◽  
Fernando Larrea ◽  
Mayel Chirinos
Keyword(s):  
Emergency Contraception ◽  
Reproductive Tract ◽  
Calcium Ionophore ◽  
Human Sperm ◽  
Female Reproductive Tract ◽  
Protein Glycosylation ◽  
Glycosylation Pattern ◽  
Two Dimensional Gel Electrophoresis ◽  
Emergency Contraceptive ◽  
Uterine Secretions

When levonorgestrel (LNG) is given for emergency contraception during the follicular phase inhibits or delays ovulation, but also induces changes in endometrial secretions that modulate sperm functionality. In order to characterize the female reproductive tract secreted molecules that may affect human spermatozoa, we analyzed changes in the protein content of uterine flushings obtained from women during the periovulatory phase of a control and a LNG-treated menstrual cycle. Lectin affinity analysis and two-dimensional gel electrophoresis of uterine samples showed changes in protein glycosylation pattern and the presence of 31 differentially expressed proteins (8 up- and 23 down-regulated). Mass spectrometry and Western blot analyses of the differential expressed proteins showed lactotransferrin (LTF) as one of the up-regulated molecules by LNG. In this study, LTF exhibited significant dose-related effects on sperm functionality, particularly a decrease of calcium ionophore-induced acrosome reaction and protein tyrosine phosphorylation. Overall, the results indicated that LNG promoted changes in the proteome of uterine secretions that might compromise human sperm capacitation. These data further support the participation of other mechanisms of action of LNG as emergency contraceptive, in addition to those on ovulation.

119. IDENTIFICATION AND CHARACTERISATION OF SURFACE PROTEIN COMPLEXES IN HUMAN SPERMATOZOA

2010 ◽  
Vol 22 (9) ◽  
pp. 37 ◽  
Author(s):  
K. A. Redgrove ◽  
B. Nixon ◽  
E. A. McLaughlin ◽  
M. K. O'Bryan ◽  
R. J. Aitken
Keyword(s):  
Zona Pellucida ◽  
Reproductive Tract ◽  
Protein Complexes ◽  
Polyacrylamide Gel Electrophoresis ◽  
Human Sperm ◽  
Female Reproductive Tract ◽  
Human Spermatozoa ◽  
Apical Region ◽  
Post Translational Modification ◽  
Cellular Mechanisms

A unique characteristic of mammalian spermatozoa is that upon ejaculation, they are unable to recognise and bind to an ovulated oocyte. These functional attributes are only realised following the sperms ascent of the female reproductive tract whereupon they undergo a myriad of biochemical and biophysical changes collectively referred to as ‘capacitation’. Since spermatozoa are both transcriptionally and translationally quiescent cells, this functional transformation must be engineered by a combination of post-translational modification and spatial reorganisation of existing sperm proteins. Indeed, evidence from our laboratory suggests that a key attribute of capacitation is the remodeling of the sperm surface architecture leading to the assembly and / or presentation of multimeric sperm-oocyte receptor complex(es). Through the novel application of Blue Native Polyacrylamide Gel Electrophoresis (BN-PAGE), we have secured the first direct evidence that human spermatozoa express a number of these protein complexes on their surface. Furthermore, we have demonstrated that a subset of these complexes harbour putative zona adhesion proteins and display strong affinity for solubilised zona pellucidae. In this study, we have extended our findings through the characterisation of one such complex containing arylsulfatase A (ASA), a protein with recognised affinity for sulfated ligands present within the zona pellucida. Through the application of immunohistochemistry and flow cytometry we revealed that ASA undergoes a capacitation-associated translocation to become expressed on the apical region of the human sperm head, a location compatible with a role in the mediation of sperm-zona pellucida interactions. This dramatic relocation was completely abolished by incubation of capacitating spermatozoa in exogenous cholesterol, suggesting that it may be driven in part by alteration in the membrane fluidity characteristics. Our current research is focused on confirming the role of ASA in human sperm-zona pellucida adhesion and elucidating the precise cellular mechanisms that underpin the proteins translocation to the cell surface.

scholarly journals Human sperm uses asymmetric and anisotropic flagellar controls to regulate swimming symmetry and cell steering

2020 ◽  
Vol 6 (31) ◽  
pp. eaba5168 ◽  
Author(s):  
Hermes Gadêlha ◽  
Paul Hernández-Herrera ◽  
Fernando Montoya ◽  
Alberto Darszon ◽  
Gabriel Corkidi
Keyword(s):  
High Speed ◽  
Reproductive Tract ◽  
Three Dimensional ◽  
Human Sperm ◽  
Bilateral Symmetry ◽  
Female Reproductive Tract ◽  
Optical Illusion ◽  
3D Microscopy ◽  
Molecular Components ◽  
Molecular Asymmetries

Flagellar beating drives sperm through the female reproductive tract and is vital for reproduction. Flagellar waves are generated by thousands of asymmetric molecular components; yet, paradoxically, forward swimming arises via symmetric side-to-side flagellar movement. This led to the preponderance of symmetric flagellar control hypotheses. However, molecular asymmetries must still dictate the flagellum and be manifested in the beat. Here, we reconcile molecular and microscopic observations, reconnecting structure to function, by showing that human sperm uses asymmetric and anisotropic controls to swim. High-speed three-dimensional (3D) microscopy revealed two coactive transversal controls: An asymmetric traveling wave creates a one-sided stroke, and a pulsating standing wave rotates the sperm to move equally on all sides. Symmetry is thus achieved through asymmetry, creating the optical illusion of bilateral symmetry in 2D microscopy. This shows that the sperm flagellum is asymmetrically controlled and anisotropically regularized by fast-signal transduction. This enables the sperm to swim forward.

scholarly journals Uterine flushings from women treated with levonorgestrel affect sperm functionality in vitro

Reproduction ◽  
2017 ◽  
Vol 154 (5) ◽  
pp. 607-614 ◽  
Author(s):  
Mayel Chirinos ◽  
Marta Durand ◽  
María Elena González-González ◽  
Gabriela Hernández-Silva ◽  
Israel Maldonado-Rosas ◽  
...  
Keyword(s):  
Tyrosine Phosphorylation ◽  
Emergency Contraception ◽  
Acrosome Reaction ◽  
Binding Capacity ◽  
Human Sperm ◽  
Contraceptive Efficacy ◽  
Serum Luteinizing Hormone ◽  
Emergency Contraceptive ◽  
Testosterone Derivative

Levonorgestrel (LNG), a synthetic 19 nor-testosterone derivative, is widely used for emergency contraception. It is well known that LNG prevents ovulation only when given prior to the surge of serum luteinizing hormone (LH) during the periovulatory phase of the menstrual cycle. This observation suggests that LNG, given its contraceptive efficacy, has additional effects other than those affecting ovulation. In this study, we have evaluated the effects on human sperm functionality of uterine flushings (UF) obtained from women at day LH + 1 of a control cycle (CTR-LH + 1) and after receiving LNG (LNG-LH + 1) two days before the surge of LH. Human sperm from normozoospermic donors were incubated with UF and protein tyrosine phosphorylation, sperm motility, acrosome reaction as well as zona pellucida (ZP) binding capacity were assessed. A significant decrease in total motility and tyrosine phosphorylation accompanied by an increase on spontaneous acrosome reaction was observed when sperm were incubated in the presence of LNG-LH + 1. None of these effects were mimicked by purified glycodelin A (GdA). Moreover, the addition of UF obtained during the periovulatory phase from LNG-treated women or the presence of purified GdA significantly decreased sperm-ZP binding. The data were compatible with changes affecting sperm capacitation, motility and interaction with the ZP. These results may offer evidence on additional mechanisms of action of LNG as an emergency contraceptive.

scholarly journals Mobilisation of Ca2+ stores and flagellar regulation in human sperm by S-nitrosylation: a role for NO synthesised in the female reproductive tract

Development ◽  
2008 ◽  
Vol 135 (22) ◽  
pp. 3677-3686 ◽  
Author(s):  
G. Machado-Oliveira ◽  
L. Lefievre ◽  
C. Ford ◽  
M. B. Herrero ◽  
C. Barratt ◽  
...  
Keyword(s):  
Reproductive Tract ◽  
Human Sperm ◽  
Female Reproductive Tract

Glyco-scope into the Role of Protein Glycosylation in the Female Reproductive Tract

2020 ◽  
Vol 32 (186) ◽  
pp. E53-E61
Author(s):  
Abdulrahman M. Shathili ◽  
David C. L. Handler ◽  
Nicolle H. Packer
Keyword(s):  
Reproductive Tract ◽  
Female Reproductive Tract ◽  
Protein Glycosylation

Engineering sperm-binding IgG antibodies for the development of an effective nonhormonal female contraception

2021 ◽  
Vol 13 (606) ◽  
pp. eabd5219
Author(s):  
Bhawana Shrestha ◽  
Alison Schaefer ◽  
Yong Zhu ◽  
Jamal Saada ◽  
Timothy M. Jacobs ◽  
...  
Keyword(s):  
Biomedical Applications ◽  
Reproductive Tract ◽  
Human Sperm ◽  
Female Reproductive Tract ◽  
Infertile Woman ◽  
Igg Antibodies ◽  
Contraceptive Methods ◽  
Sperm Binding ◽  
Polyvalent Immunoglobulins ◽  
Unique Surface

Many women risk unintended pregnancy because of medical contraindications or dissatisfaction with contraceptive methods, including real and perceived side effects associated with the use of exogenous hormones. We pursued direct vaginal delivery of sperm-binding monoclonal antibodies (mAbs) that can limit progressive sperm motility in the female reproductive tract as a strategy for effective nonhormonal contraception. Here, motivated by the greater agglutination potencies of polyvalent immunoglobulins but the bioprocessing ease and stability of immunoglobulin G (IgG), we engineered a panel of sperm-binding IgGs with 6 to 10 antigen-binding fragments (Fabs), isolated from a healthy immune-infertile woman against a unique surface antigen universally present on human sperm. These highly multivalent IgGs (HM-IgGs) were at least 10- to 16-fold more potent and faster at agglutinating sperm than the parent IgG while preserving the crystallizable fragment (Fc) of IgG that mediates trapping of individual spermatozoa in mucus. The increased potencies translated into effective (>99.9%) reduction of progressively motile sperm in the sheep vagina using as little as 33 μg of the 10-Fab HM-IgG. HM-IgGs were produced at comparable yields and had identical thermal stability to the parent IgG, with greater homogeneity. HM-IgGs represent not only promising biologics for nonhormonal contraception but also a promising platform for engineering potent multivalent mAbs for other biomedical applications.

scholarly journals Effects of lactoferrin, a protein present in the female reproductive tract, on parameters of human sperm capacitation and gamete interaction

Andrology ◽  
2015 ◽  
Vol 3 (6) ◽  
pp. 1068-1075 ◽  
Author(s):  
C. M. Zumoffen ◽  
E. Massa ◽  
A. M. Caille ◽  
M. J. Munuce ◽  
S. A. Ghersevich
Keyword(s):  
Reproductive Tract ◽  
Human Sperm ◽  
Female Reproductive Tract ◽  
Sperm Capacitation ◽  
Gamete Interaction

scholarly journals Assessment of Human Sperm Function After Recovery from the Female Reproductive Tract

1984 ◽  
Vol 31 (5) ◽  
pp. 888-894 ◽  
Author(s):  
John E. Gould ◽  
James W. Overstreet ◽  
Fredrick W. Hanson
Keyword(s):  
Reproductive Tract ◽  
Human Sperm ◽  
Female Reproductive Tract ◽  
Sperm Function

scholarly journals Expression of cystatin C in the female reproductive tract and its effect on human sperm capacitation

2018 ◽  
Vol 16 (1) ◽  
Author(s):  
Robert Kuo-Kuang Lee ◽  
Huan-Chin Tseng ◽  
Yuh-Ming Hwu ◽  
Chi-Chen Fan ◽  
Ming-Huei Lin ◽  
...  
Keyword(s):  
Cystatin C ◽  
Reproductive Tract ◽  
Human Sperm ◽  
Female Reproductive Tract ◽  
Sperm Capacitation
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