scholarly journals Mechanism of semen liquefaction and its potential for a novel non-hormonal contraception†

2020 ◽  
Vol 103 (2) ◽  
pp. 411-426
Author(s):  
Prashanth Anamthathmakula ◽  
Wipawee Winuthayanon

Abstract Semen liquefaction is a proteolytic process where a gel-like ejaculated semen becomes watery due to the enzymatic activity of prostate-derived serine proteases in the female reproductive tract. The liquefaction process is crucial for the sperm to gain their motility and successful transport to the fertilization site in Fallopian tubes (or oviducts in animals). Hyperviscous semen or failure in liquefaction is one of the causes of male infertility. Therefore, the biochemical inhibition of serine proteases in the female reproductive tract after ejaculation is a prime target for novel contraceptive development. Herein, we will discuss protein components in the ejaculates responsible for semen liquefaction and any developments of contraceptive methods in the past that involve the liquefaction process.

1999 ◽  
Vol 46 (4) ◽  
pp. 935-939 ◽  
Author(s):  
D Hołody ◽  
J Strzezek

Low molecular mass, heparin-binding proteins from seminal plasma play an important role in gametes interaction whereas plasmatic Zn2+-binding proteins stabilize chromatin and plasmalemma structures and protect spermatozoa in the female reproductive tract. By means of affinity chromatography the heparin- and Zn2+-binding proteins were isolated from boar seminal plasma and both preparations were analyzed by reverse HPLC. Most of the proteins bound to heparine and Zn2+-ions were classified as spermadhesins. Three fractions binding exclusively Zn2+ were isolated. They differ in amino-acid composition, content of glucosamine and content of protein components revealed by SDS/PAGE.


2020 ◽  
Vol 28 (1) ◽  
pp. 35-51 ◽  
Author(s):  
Lama Alzamil ◽  
Konstantina Nikolakopoulou ◽  
Margherita Y. Turco

AbstractBoth the proper functioning of the female reproductive tract (FRT) and normal placental development are essential for women’s health, wellbeing, and pregnancy outcome. The study of the FRT in humans has been challenging due to limitations in the in vitro and in vivo tools available. Recent developments in 3D organoid technology that model the different regions of the FRT include organoids of the ovaries, fallopian tubes, endometrium and cervix, as well as placental trophoblast. These models are opening up new avenues to investigate the normal biology and pathology of the FRT. In this review, we discuss the advances, potential, and limitations of organoid cultures of the human FRT.


2021 ◽  
Vol 13 (606) ◽  
pp. eabd5219
Author(s):  
Bhawana Shrestha ◽  
Alison Schaefer ◽  
Yong Zhu ◽  
Jamal Saada ◽  
Timothy M. Jacobs ◽  
...  

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.


2011 ◽  
Vol 11 (1) ◽  
Author(s):  
Emiliano Mancini ◽  
Federica Tammaro ◽  
Francesco Baldini ◽  
Allegra Via ◽  
Domenico Raimondo ◽  
...  

1956 ◽  
Vol 13 (2) ◽  
pp. 133-140 ◽  
Author(s):  
T. MANN ◽  
C. POLGE ◽  
L. E. A. ROWSON

SUMMARY Chemical methods for the analysis of three characteristic constituents of seminal plasma, namely, fructose, citric acid and ergothioneine, were applied in an attempt to evaluate in a quantitative manner the participation of seminal plasma in the passage of sperm along the female reproductive tract of two species, the pig and the horse. At specified intervals after mating, the reproductive tract of the gilt and the mare, respectively, was exposed, the uterine horns and Fallopian tubes clamped into several segments and the contents of the isolated portions withdrawn for analysis. In the gilt, about 40 min after mating, the uterine horns were found to be filled with semen containing spermatozoa, as well as fructose, ergothioneine and citric acid, but 6 hr after mating the bulk of sperm and seminal plasma had disappeared. In the mare, 50 min after mating, spermatozoa, ergothioneine and citric acid were recovered from both uterine horns, in proportions resembling those found in fresh stallion semen.


Endometriosis is a chronic disease of the female reproductive system, which is characterised by the presence of endometrial tissue outside the uterus especially in the pelvic cavity that includes ovaries, fallopian tubes and it may occur extra genitally in some rare cases. 176 million women all over the world including 26 million in India suffer from endometriosis and high frequency was observed between the age group of 26-30 years, resulting in increased primary infertility. Various studies surveying the female reproductive tract have confirmed the existence of microbiota starting in the vagina, cervix, uterus, fallopian tubes and ovaries. These microbes play a crucial role at different stages ofthe reproduction, in forming a physical barrier against pathogen and the stimulation of host defence mechanisms. Direct and indirect mechanisms are observed including the production of biochemically active compounds that directly kill or inhibit pathogens. Women suffering from endometriosis lead an impaired quality of life and continue to deal with endometriosis-associated symptoms even after diagnosis and treatment of the disease. In endometriosis condition, adhesions are observed in the fallopian tubes and ovaries that block tubal motility and damage the oocyte-pickup. Progesterone resistance is familiar in endometriosis which changes the implantation window period causing the loss of implantation markers and finally leading to infertility. Malignant tumours of ovaries have also been identified and known to arise from endometriosis. Microbiome can be used as a novel diagnostic tool for endometriosis as there is a variation observed in the composition and distribution along the female reproductive tract of healthy women and endometriosis patients. A non-invasive diagnosis is achieved through this, aiming at early diagnosis and alternative treatment for endometriosis.


2004 ◽  
Vol 72 (10) ◽  
pp. 5799-5806 ◽  
Author(s):  
Patricia A. Pioli ◽  
Eyal Amiel ◽  
Todd M. Schaefer ◽  
John E. Connolly ◽  
Charles R. Wira ◽  
...  

ABSTRACT Toll-like receptor (TLR) signal transduction is a central component of the innate immune response to pathogenic challenge. Although recent studies have begun to elucidate differences in acquired immunity in tissues of the human female reproductive tract, there is a relative paucity of work regarding innate defense mechanisms. We investigated TLR mRNA and protein expression in tissues of the human female reproductive tract. Constitutive mRNA expression of TLRs 1 to 6 was observed in fallopian tubes, uterine endometrium, cervix, and ectocervix. Furthermore, transcripts of the signaling adapter MyD88 and the accessory molecule CD14 were also detected in all tissues assayed. Quantitative analysis of TLR2 mRNA levels revealed highest expression of this molecule in fallopian tube and cervical tissues, followed by endometrium and ectocervix. In contrast to TLR2, TLR4 expression declined progressively along the tract, with highest expression in the upper tissues (fallopian tubes and endometrium), followed by cervix and ectocervix. In addition to mRNA, protein expression of TLR2 and TLR4 was also documented in these tissues. These data suggest that TLRs are differentially expressed in distinct compartments of the female reproductive tract and may provide insight regarding the regulation of inflammation and immunity within the tract.


1955 ◽  
Vol 13 (1) ◽  
pp. 26-38 ◽  
Author(s):  
CECILIA LUTWAK-MANN

SUMMARY Carbonic anhydrase was shown to occur in the female reproductive tract of a variety of mammalian species. The uterine endometrium, placental tissue and the Fallopian tubes were established as the main loci of carbonic anhydrase activity. The enzyme was present in the endometrium of the non-pregnant rabbit in a low concentration. Following mating no perceptible increase in enzyme content occurred before the 4th day; from then onwards the activity continued to rise, reaching a maximum by about the 8th day; with advancing foetal development the endometrial activity declined, but at the same time the enzyme could be demonstrated in the placenta, chiefly in the maternal, but to a small extent also in the foetal, part. The behaviour of carbonic anhydrase in the pseudopregnant uterus or in response to ovulating doses of gonadotrophin or copper salts, presented essentially the same picture as in the early phase of pregnancy; excessive doses of gonadotrophin were capable of increasing the enzyme content within 2 days of administration; moreover, their effect persisted for 20–24 days. Progesterone, and to a smaller extent ethisterone and methyltestosterone, injected into oestrous adult or into oestrogen-primed immature rabbits, produced marked increases in the content of uterine carbonic anhydrase, the extent of which depended upon the dose. Whereas the endometrium of rats, hamsters and guinea-pigs was completely devoid of carbonic anhydrase, both in pregnant and non-pregnant females, the placenta of these animals contained the enzyme, again mainly in the maternal portion. The uterine mucosa of the non-pregnant sheep was conspicuously rich in carbonic anhydrase, the activity being largely restricted to the intercotyledonary areas; the uterine portion of the Fallopian tubes was also remarkably active. In this species the uterine carbonic anhydrase was found to be independent of ovarian function: the enzyme was present in the uteri of prepubertal lambs, and it was fully preserved in ovariectomized animals. Considerable enzymic activity was found in the sheep placenta. No carbonic anhydrase was found in the uterus or Fallopian tubes of the non-pregnant pig; the pig placenta, however, was very active, the enzyme being located in the chorion in late pregnancy. In the non-pregnant cow only the fimbrial portion of the Fallopian tubes showed enzymic activity, especially marked in the immediate post-ovulatory phase. No carbonic anhydrase was present in the non-pregnant uteri or Fallopian tubes of mares, cats or dogs. By introducing parenterally large amounts of a sulphonamide inhibitor of carbonic anhydrase it was possible to inhibit the enzyme in vivo, both in the rat placenta and in the progestational rabbit endometrium.


F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1666
Author(s):  
Carla M.J. Muytjens ◽  
Yijing Yu ◽  
Eleftherios P. Diamandis

Background: Cervical-vaginal fluid (CVF) hydrates the mucosa of the lower female reproductive tract and is known to contain numerous proteases. The low pH of CVF (4.5 or below in healthy women of reproductive age) is a uniquely human attribute and poses a challenge for the proteolytic functioning of the proteases identified in this complex biological fluid. Despite the abundance of certain proteases in CVF, the proteolytic activity and function of proteases in CVF is not well characterized.Methods: In the present study, we employed fluorogenic substrate screening to investigate the influence of pH and inhibitory compounds on the proteolytic activity in CVF. Activity-based probe (ABP) proteomics has evolved as a powerful tool to investigate active proteases within complex proteomes and a trypsin-specific ABP was used to identify active proteases in CVF.Results: Serine proteases are among the most abundant proteins in the CVF proteome. Labeling human CVF samples with the trypsin-specific ABP revealed serine proteases transmembrane protein serine 11D and kallikrein-related peptidase 13 as active proteases in CVF. Furthermore, we demonstrated that the proteolytic activity in CVF is highly pH-dependent with an almost absolute inhibition of trypsin-like proteolytic activity at physiological pH levels.Conclusions: These findings provide a framework to understand proteolytic activity in CVF. Furthermore, the present results provide clues for a novel regulatory mechanism in which fluctuations in CVF pH have the potential to control the catalytic activity in the lower female reproductive tract.


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