Epididymal antimicrobial peptides: the role in sperm function (review)

Значительное снижение показателей мужской фертильности, наблюдаемое в последнее время во всем мире, ведёт к необходимости более глубокого изучения механизмов молекулярной регуляции гаметогенеза и посттестикулярной трансформации сперматозоидов. Совершенствование способов влияния на эти процессы, а также поиск веществ, повышающих устойчивость гамет к действию различных повреждающих факторов, открывают перспективы разработки новых подходов в лечении мужского бесплодия. В связи с этим актуальным направлением является исследование роли эндогенных антимикробных пептидов и их физиологической активности при созревании и функционировании мужских половых клеток. Антимикробные пептиды - это уникальные компоненты системы врожденного иммунитета. Они не только обеспечивают противоинфекционную защиту организма от бактерий, вирусов и грибов, но и проявляют достаточно разнообразные биологические эффекты, которые связаны, в том числе и со способностью этих молекул принимать непосредственное участие в физиологических процессах посттестикулярного созревания половых клеток, модификации цитоплазматических мембран сперматозоидов в эпидидимисе, а также капацитации в женском репродуктивном тракте. В настоящем обзоре рассмотрены современные представления о роли антимикробных пептидов придатков яичек с позиций их участия в функционировании сперматозоидов в норме и при патологии. The significant worldwide decline in male fertility requires a comprehensive study of molecular regulatory mechanisms of gametogenesis and post-testicular sperm maturation. Improving ways to influence these processes as well as searching for substances that increase the resistance of gametes to the action of various damaging factors open up prospects for development of new approaches to treat male infertility. In this regard, current emphasis is on the study of a role of endogenous antimicrobial peptides (AMPs) and their physiological activity during the maturation and functioning of male germ cells. AMPs are unique components of the innate immune system. They not only provide protection against bacteria, viruses, and fungi, but also have relatively diverse biological effects. These effects are closely related to the ability of AMPs to be directly involved in the physiological processes of post-testicular maturation of germ cells, in modification of the plasma membranes of sperms in the epididymis, and their capacitation in the female reproductive tract. This review focuses on the current understanding of the role of epididymal AMPs with regard to the functioning of sperm in normal and pathological conditions.

Download Full-text

Antimicrobial peptides in the pathogenesis of infectious complications in obstetrics and gynecology

Journal of obstetrics and women s diseases ◽

10.17816/jowd63573-81 ◽

2014 ◽

Vol 63 (5) ◽

pp. 73-81 ◽

Cited By ~ 1

Author(s):

Olesya Nikolaevna Ivashova ◽

Olga Petrovna Lebedeva ◽

Sergey Petrovich Pakhomov ◽

Natal’ya Alexandrovna Rudyh ◽

Marina Sergeevna Seliverstova

Keyword(s):

Antimicrobial Peptides ◽

Reproductive Tract ◽

Infectious Complications ◽

Female Reproductive Tract ◽

Innate Immune ◽

Cationic Peptides ◽

Practical Application ◽

Sexually Transmitted ◽

Angiogenic Effect

Antimicrobial peptides (AMP) are cationic peptides of innate immune system with antiviral, antibacterial and antiprotozoal activity. AMP act as immunomodulators, promote bacterial opsonization, inhibit proteases activity, have anti-endotoxic and angiogenic effect. The review describes main types of AMPs, features of their expression in female reproductive tract depending from menstrual cycle and during pregnancy. Data about the role of AMPs in defending from sexually transmitted infections (HIV, genital herpes, HPV, gonorrhea), in pathogenesis of extrauterine pregnancy and preterm birth are described. Possibility of practical application of AMPs as alternative to antibiotics and as contraceptives is estimated.

Download Full-text

The Central Role of Cadherins in Gonad Development, Reproduction and Fertility

10.20944/preprints202010.0037.v1 ◽

2020 ◽

Author(s):

Rafał P. Piprek ◽

Malgorzata Kloc ◽

Paulina Mizia ◽

Jacek Z. KUBIAK

Keyword(s):

Germ Cells ◽

Reproductive Tract ◽

Primordial Germ Cells ◽

Somatic Cells ◽

Gonad Development ◽

Female Reproductive Tract ◽

Future Research ◽

Corpora Lutea ◽

Germline Development

Cadherins are a group of membrane proteins responsible for cell adhesion. They are crucial for cell sorting and recognition during the morphogenesis, but also play many other roles such as assuring tissue integrity and resistance to stretching, mechanotransduction, cell signaling, regulation of cell proliferation, apoptosis, survival, carcinogenesis, etc. Within the cadherin superfamily, the E- and N-cadherin have been especially well studied. They are involved in many aspects of sexual development and reproduction, such as germline development and gametogenesis, gonad development and functioning, and fertilization. E-cadherin is expressed in the primordial germ cells, (PGCs) and also participates in PGC migration to the developing gonads where they become enclosed by the N-cadherin-expressing somatic cells. The differential expression of cadherins is also responsible for the establishment of the testis or ovary structure. In the adult testes, the N-cadherin is responsible for the integrity of the seminiferous epithelium, regulation of sperm production, and the establishment of the blood-testis barrier. Sex hormones regulate the expression and turnover of N-cadherin influencing the course of spermatogenesis. In the adult ovaries, E- and N-cadherin assure the integrity of ovarian follicles and the formation of corpora lutea. Cadherins are expressed in the mature gametes, and facilitate the capacitation of sperm in the female reproductive tract, and gamete contact during fertilization. The germ cells and accompanying somatic cells express a series of different cadherins, however, their role in gonads and reproduction is still unknown. In this review, we show what is known and unknown about the role of cadherins in the germline and gonad development, and suggest the topics for future research.

Download Full-text

The Central Role of Cadherins in Gonad Development, Reproduction, and Fertility

International Journal of Molecular Sciences ◽

10.3390/ijms21218264 ◽

2020 ◽

Vol 21 (21) ◽

pp. 8264

Author(s):

Rafał P. Piprek ◽

Malgorzata Kloc ◽

Paulina Mizia ◽

Jacek Z. Kubiak

Keyword(s):

Germ Cells ◽

Reproductive Tract ◽

Primordial Germ Cells ◽

Somatic Cells ◽

Gonad Development ◽

Female Reproductive Tract ◽

Future Research ◽

Corpora Lutea ◽

Germline Development

Cadherins are a group of membrane proteins responsible for cell adhesion. They are crucial for cell sorting and recognition during the morphogenesis, but they also play many other roles such as assuring tissue integrity and resistance to stretching, mechanotransduction, cell signaling, regulation of cell proliferation, apoptosis, survival, carcinogenesis, etc. Within the cadherin superfamily, E- and N-cadherin have been especially well studied. They are involved in many aspects of sexual development and reproduction, such as germline development and gametogenesis, gonad development and functioning, and fertilization. E-cadherin is expressed in the primordial germ cells (PGCs) and also participates in PGC migration to the developing gonads where they become enclosed by the N-cadherin-expressing somatic cells. The differential expression of cadherins is also responsible for the establishment of the testis or ovary structure. In the adult testes, N-cadherin is responsible for the integrity of the seminiferous epithelium, regulation of sperm production, and the establishment of the blood–testis barrier. Sex hormones regulate the expression and turnover of N-cadherin influencing the course of spermatogenesis. In the adult ovaries, E- and N-cadherin assure the integrity of ovarian follicles and the formation of corpora lutea. Cadherins are expressed in the mature gametes and facilitate the capacitation of sperm in the female reproductive tract and gamete contact during fertilization. The germ cells and accompanying somatic cells express a series of different cadherins; however, their role in gonads and reproduction is still unknown. In this review, we show what is known and unknown about the role of cadherins in the germline and gonad development, and we suggest topics for future research.

Download Full-text

Phosphodiesterase Activities in the Eye of Old and Young Rats in Normoxic, Hypoxic and Hyperoxic Atmospheres

European Journal of Inflammation ◽

10.1177/1721727x0300100106 ◽

2003 ◽

Vol 1 (1) ◽

pp. 25-32 ◽

Cited By ~ 1

Author(s):

G. Spoto ◽

A. Contento ◽

M. Di Nicola ◽

G. Bianchi ◽

C. Di Giulio ◽

...

Keyword(s):

Cyclic Nucleotides ◽

Biological Effects ◽

Atmospheric Oxygen ◽

Second Messengers ◽

Camp Phosphodiesterase ◽

Young Rats ◽

Physiological Processes ◽

Adaptive Processes ◽

Old Rats

Phosphodiesterase activity was tested on homogenized eyes of young and old rats kept in hypoxic and hyperoxic conditions, with the aim of correlating any difference in PDE activity with aging and variations in atmospheric oxygen contents. The activities of the two enzymes, cAMP phosphodiesterase (cAMP-PDE) and cGMP phosphodiesterase (cGMP-PDE), were tested. Phosphodiesterases seem to be particularly susceptible to variations in oxygen tension, suggesting an important role of cyclic nucleotides in cellular adaptive processes. Particularly, cAMP-PDE activity increases lightly both in hypoxic and hyperoxic conditions in young and old rats. For cGMP-PDE activity of young rats, a similar behaviour to cAMP-PDE activity is observed with a similar increase in hypoxic and hyperoxic conditions respect to the control rats. Instead old rats seem to be quite insensible to hypoxia, while they show a fair increase in cGMP-PDE activity in the case of hyperoxia. The second messengers cAMP and cGMP play important roles in mediating the biological effects of a wide variety of first messengers. The intracellular levels of cyclic nucleotides depend upon rates of synthesis and degradation, actuated, respectively, by cyclases and phosphodiesterases (PDEs). Therefore, PDEs seem to play an important role in a wide variety of physiological processes.

Download Full-text

Vitamin D Status Impacts Genital Mucosal Immunity and Markers of HIV-1 Susceptibility in Women

Nutrients ◽

10.3390/nu12103176 ◽

2020 ◽

Vol 12 (10) ◽

pp. 3176

Author(s):

Sharon M. Anderson ◽

Andrea R. Thurman ◽

Neelima Chandra ◽

Suzanne S. Jackson ◽

Susana Asin ◽

...

Keyword(s):

Vitamin D ◽

Reproductive Tract ◽

Serum Vitamin ◽

Female Reproductive Tract ◽

High Dose ◽

Vitamin D Status ◽

Serum Vitamin D ◽

Vitamin D Levels ◽

Hiv 1

While vitamin D insufficiency is known to impact a multitude of health outcomes, including HIV-1, little is known about the role of vitamin D-mediated immune regulation in the female reproductive tract (FRT). We performed a pilot clinical study of 20 women with circulating 25(OH)D levels <62.5 nmol/L. Participants were randomized into either weekly or daily high-dose oral vitamin D supplementation groups. In addition to serum vitamin D levels, genital mucosal endpoints, including soluble mediators, immune cell populations, gene expression, and ex vivo HIV-1 infection, were assessed. While systemic vitamin D levels showed a significant increase following supplementation, these changes translated into modest effects on the cervicovaginal factors studied. Paradoxically, post-supplementation vitamin D levels were decreased in cervicovaginal fluids. Given the strong correlation between vitamin D status and HIV-1 infection and the widespread nature of vitamin D deficiency, further understanding of the role of vitamin D immunoregulation in the female reproductive tract is important.

Download Full-text

Do spermathecal morphology and inter-mating interval influence paternity in the polyandrous beetle Tribolium castaneum?

Behaviour ◽

10.1163/156853906776759538 ◽

2006 ◽

Vol 143 (5) ◽

pp. 643-658 ◽

Cited By ~ 6

Author(s):

Ludovic Arnaud ◽

Giorgina Bernasconi ◽

Yves Brostaux ◽

Eric P. Meyer

Keyword(s):

Sperm Competition ◽

Tribolium Castaneum ◽

Reproductive Tract ◽

Sperm Storage ◽

Female Reproductive Tract ◽

Phenotypic Marker ◽

Male And Female ◽

The Difference ◽

Different Strains

AbstractIn polyandrous insects, postcopulatory sexual selection is a pervasive evolutionary force favouring male and female traits that allow control of offspring paternity. Males may influence paternity through adaptations for sperm competition, and females through adaptations facilitating cryptic female choice. Yet, the mechanisms are often complex, involving behaviour, physiology or morphology, and they are difficult to identify. In red flour beetles (Tribolium castaneum), paternity varies widely, and evidence suggests that both male and female traits influence the outcome of sperm competition. To test the role of spermathecal morphology and of sperm storage processes on the outcome of sperm competition, we mated each of 26 virgin females with two males, one of which carrying a phenotypic marker to assign offspring paternity. We manipulated the interval between mating with the first and the second male, to create different conditions of sperm storage (overlapping and non-overlapping) in the female reproductive tract. To investigate the role of sperm storage more closely, we examined the relationship between paternity and spermathecal morphology in a subset of 14 experimental females. In addition, we also characterized variation in spermathecal morphology in three different strains, wildtype, Chicago black and Reindeer. No significant influence of the intermating interval was found on the paternity of the focal male, although the direction of the difference was in the expected direction of higher last male paternity for longer intervals. Moreover, paternity was not significantly associated with spermathecal morphology, although spermathecal volume, complexity, and tubule width varied significantly and substantially among individuals in all investigated strains.

Download Full-text

Behavioural cycles during Pseudopregnancy in confined populations of domestic rabbits and their relation to the histology of the female reproductive tract

Australian Journal of Zoology ◽

10.1071/zo9660173 ◽

1966 ◽

Vol 14 (2) ◽

pp. 173 ◽

Cited By ~ 3

Author(s):

RL Hughes ◽

K Myers

Keyword(s):

Reproductive Tract ◽

Sexual Attraction ◽

Physiological Activity ◽

Adaptive Significance ◽

Female Reproductive Tract ◽

Corpora Lutea ◽

Weight Changes ◽

Dimensional Changes ◽

Detectable Difference ◽

Domestic Rabbits

Female domestic rabbits living with vasectomized males in large compounds (3/16 ac in area) exhibited periods of sexual attraction and mating, together with other behaviour such as aggression towards other females, digging, burrow interest, and nest building at intervals of about 6 days or multiples thereof. The behavioural cycles occurred during pseudopregnancy (of about 18 days) and were not a manifestation of an underlying inherent sequential cycle or a typical mammalian oestrous cycle. Behaviour with a strong sexual component culminating in mating and ovulation was observed at the beginning (or end) of each of 54 pseudopregnancies. Similar behaviour was also grouped about either the sixth or twelfth days of pseudopregnancy or both. This behaviour was extremely variable in both incidence and the number of components involved. Sexual components occurred less frequently and only once culminated in mating and ovulation. The behaviour observed on the sixth and twelfth days of pseudopregnancy was not reflected in measures of physiological activity such as numbers of graafian follicles, diameter of graafian follicles or corpora lutea, or weight changes in ovaries or uteri. The histology of the ovaries, uterus, and vagina and dimensional changes such as ovarian and uterine weights, number and diameter of graafian follicles, and diameter of sets of corpora lutea showed no detectable difference from those reported by other workers during pseudopregnancy for caged female rabbits isolated from males. The incidence of 6-day and 12-day behaviour was highest in the autumn-winter months when sub-optimal reproductiveconditions prevailed and lowest in spring-summer. Some possible causal mechanisms and the adaptive significance of the sixth-day and twelfth-day periods of sexual behaviour are discussed.

Download Full-text

ESR1 Mutations Associated With Estrogen Insensitivity Syndrome Change Conformation of Ligand-Receptor Complex and Altered Transcriptome Profile

Endocrinology ◽

10.1210/endocr/bqaa050 ◽

2020 ◽

Vol 161 (6) ◽

Cited By ~ 1

Author(s):

Yin Li ◽

Katherine J Hamilton ◽

Lalith Perera ◽

Tianyuan Wang ◽

Artiom Gruzdev ◽

...

Keyword(s):

Molecular Mechanisms ◽

Reproductive Tract ◽

Biological Effects ◽

Estrogen Receptor Α ◽

Female Reproductive Tract ◽

Receptor Complexes ◽

Esr1 Gene ◽

Esr1 Mutations

Abstract Estrogen insensitivity syndrome (EIS) arises from rare mutations in estrogen receptor-α (ERα, encoded by ESR1 gene) resulting in the inability of estrogen to exert its biological effects. Due to its rarity, mutations in ESR1 gene and the underlying molecular mechanisms of EIS have not been thoroughly studied. Here, we investigate known ESR1 mutants, Q375H and R394H, associated with EIS patients using in vitro and in vivo systems. Comparison of the transcriptome and deoxyribonucleic acid methylome from stable cell lines of both Q375H and R394H clinical mutants shows a differential profile compared with wild-type ERα, resulting in loss of estrogen responsiveness. Molecular dynamic simulation shows that both ESR1 mutations change the ERα conformation of the ligand-receptor complexes. Furthermore, we generated a mouse model Esr1-Q harboring the human mutation using CRISPR/Cas9 genome editing. Female and male Esr1-Q mice are infertile and have similar phenotypes to αERKO mice. Overall phenotypes of the Esr1-Q mice correspond to those observed in the patient with Q375H. Finally, we explore the effects of a synthetic progestogen and a gonadotropin-releasing hormone inhibitor in the Esr1-Q mice for potentially reversing the impaired female reproductive tract function. These findings provide an important basis for understanding the molecular mechanistic consequences associated with EIS.

Download Full-text