Representações sociais sobre maternidade na reprodução humana assistida: discursos de mulheres inférteis / Social representations of motherhood in assisted human reproduction: discourses of infertile women / Representaciones sociales de la maternidad en la reproducción humana asistida: relatos de mujeres infértiles

Este trabalho tem o objetivo de analisar as concepções de maternidade para mulheres inférteis de diferentes níveis socioeconômicos que estão em tratamento de reprodução assistida. Trata-se de um estudo qualitativo, descritivo, que utilizou como instrumento uma entrevista semiestruturada e contemplou temas como o significado de família, desejo/expectativas sobre filho e gestação e expectativas sobre a maternidade. Participaram da pesquisa 48 mulheres inférteis acima de 35 anos que usam tecnologias de reprodução assistida de alta complexidade em instituições privada e pública. Os dados foram tratados pela análise de conteúdo em que emergiram os temas: representações sociais da família; representações sociais da maternidade; expectativas com a gestação e os modelos maternos; e o filho imaginado. As participantes representaram a família de forma positiva, como um sistema de suporte, de fundação e origem de amor, configurando-a como um laço social. Por outro lado, as concepções de família com base na consanguinidade também estiveram presentes, representando a família pela perpetuação da espécie e pela importância do laço biológico. A maternidade foi marcada por significativa idealização, sendo vista como um papel gratificante e de realização da feminilidade. O peso da cobrança social para procriar também foi sentido como um dever a cumprir e que, na impossibilidade de se realizar, gera sentimentos de inferioridade, menos-valia, impotência e inadequação perante a sociedade, o que reforça o estigma da infertilidade. Tais resultados apontam a importância de reflexões sobre o papel da mulher na nossa cultura, visto que a maternidade é ainda utilizada como medida para o sucesso ou fracasso feminino. Faz-se necessário também refletir sobre a possibilidade da maior inserção do trabalho psicológico na reprodução assistida, visto a carga emocional e social envolvidas nesse processo.(AU)

This study aimed to analyze the conceptions of motherhood for infertile women from different socioeconomic levels who are undergoing assisted reproduction treatment. This is a qualitative and descriptive study that used a semi-structured interview as an instrument and included topics such as the meaning of family and desires/expectations about the child, pregnancy, and motherhood. A total of 48 infertile women over 35 years of ages using high-complexity assisted reproductive technologies in private and public institutions participated in this research. The data were treated by content analysis in which the following themes emerged: family social representations; social representations of motherhood; expectations with pregnancy and maternal models; and the imagined son. Participants represented the family in a positive way as a support system and the foundation and origin of love, embracing the family as a social bond. On the other hand, the family concepts based on inbreeding were also present, representing the family by perpetuation of the species and the importance of biological bonds. Motherhood was marked by significant idealization, being seen as a gratifying role and the fulfillment of femininity. The weight of the social demand to procreate was also felt as a duty to be fulfilled that, in the impossibility of carrying it out, generates feelings of inferiority, worthlessness, impotence, and inadequacy toward society, which reinforce the stigma of infertility. Results point to the necessary reflections on the role of women and our culture since Motherhood is still used as a measure of female success or failure. They also point to a reflection on the possibility of greater inclusion of psychological work in assisted reproduction given the emotional and social burden involved in this process.(AU)

Este estudio tuvo como objetivo analizar las concepciones de maternidad de mujeres infértiles, de diferentes niveles socioeconómicos, que se encuentran en tratamiento de reproducción asistida. Se trata de un estudio cualitativo, descriptivo, que utilizó como instrumento una entrevista semiestructurada e incluyó temas como el sentido de la familia, deseos/expectativas sobre el hijo y el embarazo y expectativas sobre la maternidad. Participaron en la investigación un total de 48 mujeres infértiles, mayores de 35 años, usuarias de tecnologías de reproducción asistida de alta complejidad en instituciones públicas y privadas. Los datos se sometieron a análisis de contenido del cual surgieron los temas: representaciones sociales familiares; representaciones sociales de la maternidad; expectativas con el embarazo y modelos maternos; hijo imaginado. Las participantes representaron a la familia de manera positiva, como sistema de apoyo, fundamento y origen del amor, configurándola como vínculo social. Por otro lado, también estuvieron presentes las concepciones familiares basadas en la consanguinidad, representando a la familia para la perpetuación de la especie y la importancia del vínculo biológico. La maternidad estuvo marcada por una importante idealización, vista como un rol gratificante y de realización de la feminidad. También se sintió el peso de la demanda social de procrear como un deber que cumplir y que, ante la imposibilidad de realizarlo, genera sentimientos de inferioridad, desvalorización, impotencia e inadecuación en la sociedad, lo que refuerza el estigma de la infertilidad. Por tanto, son necesarias reflexiones sobre el papel de la mujer en nuestra cultura, ya que la maternidad se sigue utilizando como medida del éxito o fracaso femenino. También se reflexiona sobre la posibilidad de una mayor inclusión del trabajo psicológico en la reproducción asistida dada la carga emocional y social que implica este proceso.(AU)

ATP activation of peritubular cells drives testicular sperm transport.

Spermatogenesis, the complex process of male germ cell proliferation, differentiation, and maturation, is the basis of male fertility. In the seminiferous tubules of the testes, spermatozoa are constantly generated from spermatogonial stem cells through a stereotyped sequence of mitotic and meiotic divisions. The basic physiological principles, however, that control both maturation and luminal transport of the still immotile spermatozoa within the seminiferous tubules remain poorly, if at all, defined. Here, we show that coordinated contractions of smooth muscle-like testicular peritubular cells provide the propulsive force for luminal sperm transport toward the rete testis. Using a mouse model for in vivo imaging, we describe and quantify spontaneous tubular contractions and show a causal relationship between peritubular Ca2+ waves and peristaltic transport. Moreover, we identify P2 receptor-dependent purinergic signaling pathways as physiological triggers of tubular contractions both in vitro and in vivo. When challenged with extracellular ATP, transport of luminal content inside the seminiferous tubules displays stage-dependent directionality. We thus suggest that paracrine purinergic signaling coordinates peristaltic recurrent contractions of the mouse seminiferous tubules to propel immotile spermatozoa to the rete testis.

As sperm develop in the testis, the immature cells must make their way through a maze of small tubes known as seminiferous tubules. However, at this stage, the cells do not yet move the long tails that normally allow them to 'swim'; it is therefore unclear how they are able to move through the tubules. Now, Fleck, Kenzler et al. have showed that, in mice, muscle-like cells within the walls of seminiferous tubules can create waves of contractions that push sperm along. Further experiments were then conducted on cells grown in the laboratory. This revealed that a signaling molecule called ATP orchestrates the moving process by activating a cascade of molecular events that result in contractions. Fleck, Kenzler et al. then harnessed an advanced microscopy technique to demonstrate that this mechanism occurs in living mice. Together, these results provide a better understanding of how sperm mature, which could potentially be relevant for both male infertility and birth control.

Sperm transport and endometrial inflammatory response in mares after artificial insemination with cryopreserved spermatozoa.

This study aimed to determine whether the insemination site and dose with cryopreserved sperm of reproductively normal mares affect the sperm population in uterine tubes and the intensity of endometrial inflammatory response. Experimental subjects were estrous mares inseminated, in the mid-uterine body (Body) or the tip of the uterine horn (Tip), ipsilateral to the dominant follicle, with one 0.5 mL straw with 50 × 106 sperm (50) or with eight straws with 50 × 106 sperm/straw (400). Mares were slaughtered 2 h, 4 h and 12 h after artificial insemination (AI) and randomly assigned to following groups: Body 50 (n = 19) (2 h, 4 h or 12 h); Tip 50 (n = 29) (2 h, 4 h, or 12 h); Body 400 (n = 24) (2 h, 4 h, or 12 h); Tip 400 (n = 21) (2 h, 4 h, or 12 h). A Control group (n = 16) was not inseminated. After slaughter, uterine tubes were separated from uterus, and uteri and tubes flushed with phosphate-buffered saline (PBS). After flushing, an endometrial sample was collected from ipsilateral and contralateral horns and mid-uterus body for further histopathological examination. A sample of each uterine tube flushing was examined for sperm count, and a sample of each uterine flushing was used for polymorphonuclear neutrophils (PMNs) count. Data were analyzed using PROC GLM from SASv9.4. Insemination time, site, sperm dose, and their interactions were considered independent variables and sperm and PMNs numbers dependent variables. Deep horn insemination increased ipsilateral uterine tube sperm number without an increase in the inflammatory reaction compared with the uterine body insemination. The higher the insemination dose, the higher the uterine tubes' sperm number and inflammatory reaction, with a quicker resolution. In conclusion, the insemination site and dose affected sperm in the uterine tubes, while post-insemination time and dose influenced the inflammatory reaction.

The role of semen and seminal plasma in inducing large-scale genomic changes in the female porcine peri-ovulatory tract.

Semen modifies the expression of genes related to immune function along the porcine female internal genital tract. Whether other pathways are induced by the deposition of spermatozoa and/or seminal plasma (SP), is yet undocumented. Here, to determine their relative impact on the uterine and tubal transcriptomes, microarray analyses were performed on the endocervix, endometrium and endosalpinx collected from pre-ovulatory sows 24 h after either mating or artificial insemination (AI) with specific ejaculate fractions containing spermatozoa or sperm-free SP. After enrichment analysis, we found an overrepresentation of genes and pathways associated with sperm transport and binding, oxidative stress and cell-to-cell recognition, such as PI3K-Akt, FoxO signaling, glycosaminoglycan biosynthesis and cAMP-related transcripts, among others. Although semen (either after mating or AI) seemed to have the highest impact along the entire genital tract, our results demonstrate that the SP itself also modifies the transcriptome. The detected modifications of the molecular profiles of the pre/peri-ovulatory endometrium and endosalpinx suggest an interplay for the survival, transport and binding of spermatozoa through, for instance the up-regulation of the Estrogen signaling pathway associated with attachment and release from the oviductal reservoir.

Implication of the estrogen receptors GPER, ESR1, ESR2 in post-testicular maturations of equine spermatozoa.

Estrogen receptors ESR1, ESR2 and GPER are present on mature ejaculated horse spermatozoa, suggesting these cells as putative targets for estrogens. Indeed, spermatozoa are exposed to high level of estrogens during the transit in the male and female genital tracts but their roles are not investigated. So, we evaluated in vitro the role of 17ß-estradiol during post-testicular maturations: regulation of motility, capacitation and acrosome reaction. Moreover according to the pseudo-seasonal breeder status of the stallion, we analyzed the putative seasonal variations in the presence of ESRs in spermatozoa. We showed that ESRs are more present on stallion sperm during the breeding season. We showed that capacitation and acrosome reaction are independent of estradiol action in horse. Estradiol can weakly modulate the motility and this effect is strictly associated with GPER and not with ESR1 and ESR2. The subcellular localization of GPER in the neck on stallion sperm is coherent with this effect. It seems that estrogens are not major regulators of sperm maturations associated to mare genital tract, so they could act during the epididymal maturations.

Optimizing the transport of porcine semen: a proposal for Brazil / Otimizar o transporte do sêmen suíno: uma proposta para o Brasil

Semen from the first 15mL of the ejaculate (P1) obtained from two boars (30mL) was diluted in glycine-egg yolk extender, cooled at 5°C in a special container and rediluted in standard doses of 3x109 mobile spermatozoa after 12h of storage. Semen was also stored up to 24h after redilution. The physical characteristics of the semen were evaluated at different storage periods (fresh, 0h, 12h, rediluted, 24h, and 36h). The reproductive performance of the boars and their fertility regarding the insemination of primiparous sows were also determined. Two treatments were used: T1-15B sows inseminated with semen originated from hyperconcentrated heterospermic doses (15x109 mobile spermatozoa per dose), rediluted after 12h of storage at 5°C for standard doses of 3x109 mobile spermatozoa per dose and stored at 5°C up to 24h after redilution (n=10); T2-3B sows inseminated with standard heterospermic doses (3x109 mobile spermatozoa per dose), stored at 5°C up to 36h after semen collection (n=10). There was no effect (P>0.05) of treatments on the spermatic motility, even though a pronounced decrease (P>0.05) of their values at 12h of storage was recorded. However, they remained higher than 70% until 36h. There was effect of treatments on spermatic vigour at 0h (P<0.05), when T1-15B vigour was higher. There was also effect of the storage period for both treatments with a progressive decrease throughout 36h of storage, although the differences were not always significant. Pregnancy rates (90%) and the number of total farrowed piglets (15, 11-T1-15B; 13, 44- T2-3B) did not differ (P>0.05) between the treatments. It was concluded that the semen hyperconcentration of 15 billion of mobile spermatozoa per dose, stored at 5°C for 12h, did not result in drawbacks considering the physical characteristics of the semen, maintaining the pregnancy rates and prolificacy of the inseminated sows.

Os primeiros 15mL do ejaculado (P1) de dois varrões foram coletados (30mL) e diluídos em diluidor glicina-gema de ovo, resfriados a 5°C em contêiner especial e rediluídos para doses padrão de 3x109 espermatozoides (sptz) móveis, após 12 horas de armazenamento. Além disso, foram armazenados por até 24 horas após a rediluição, sendo as características físicas avaliadas em diferentes períodos de estocagem (fresco, zero hora, 12h, Red12h, 24h e 36h) e a fertilidade avaliada por meio de fêmeas primíparas inseminadas. Foram realizados dois tratamentos: T1-15B: porcas inseminadas com sêmen de doses heterospérmicas hiperconcentradas (15x109 sptz móveis/dose), rediluídas após 12 horas de armazenamento a 5°C para doses padrão de 3x109 sptz móveis/dose, e armazenadas a 5°C por até 24 horas após a rediluição (n=10); T2-3B: porcas inseminadas com doses heterospérmicas padrão (3x109 sptz móveis/dose), armazenadas a 5°C por até 36 horas após coleta. Não houve efeito (P>0.05) dos tratamentos sobre a motilidade espermática e, embora tenha ocorrido queda (P<0.05) às 12 horas, a motilidade foi superior a 70% durante as 36 horas de armazenamento. Houve efeito (P<0.05) dos tratamentos no tempo zero hora quanto ao vigor espermático, sendo E1T1-15B superior. Além disso, houve efeito do período de estocagem para os dois tratamentos, com queda progressiva do vigor ao longo das 36 horas, embora nem sempre as diferenças tenham sido significativas. As taxas de gestação (90%) e o número total de leitões nascidos (15, 11 - T1-15B; 13, 44 - T2-3B) não diferiram (P>0.05) entre os tratamentos. Concluiu-se que a hiperconcentração do sêmen para 15x109 sptz móveis/dose, armazenado a 5°C por 12 horas não resultou em prejuízos quanto à manutenção das características físicas do sêmen e ao desempenho reprodutivo dos varrões, sendo capaz de manter a taxa de gestação e a prolificidade das fêmeas inseminadas.

Insights into the role of cervical mucus and vaginal pH in unexplained infertility / Sobre o papel do muco cervical e do PH vaginal na gênese da infertilidade inexplicada

Unexplained infertility diagnosis is made in the presence of a normal semen analysis when tubal patency and normal ovulatory function are established. Among several potential causes, unexplained infertility could be attributed to vaginal pH and cervical mucus abnormalities. Although the vaginal canal and the cervix generally function as effective barriers to sperm, and although the production of mucus is essential to transport them from the vagina to the uterine cavity, these factors receive little attention in the investigation of couples with unexplained infertility. A substantial reduction in sperm number occurs as they transverse the cervix. From an average of 200 to 300 million sperm deposited in the vagina, only a few hundred achieve proximity to the oocyte. Given this expected high spermatozoa loss, a slight modification in cervical mucus may rapidly transform the cervix into a "hostile" environment, which, together with changes in vaginal environment and cervix structure, may prevent natural conception and be a cause of infertility. In this review, we discuss the physiological role of the vaginal pH and cervical mucus in fertility, and describe several conditions that can render the cervical mucus hostile to sperm and therefore be implicated in the pathophysiology of unexplained infertility.

RESUMO O diagnóstico de infertilidade inexplicada baseia-se na presença de espermograma normal, constatadas também permeabilidade tubária e função ovulatória normais. Entre as várias causas potenciais de infertilidade inexplicada, a presença de muco cervical e pH vaginal anormais devem ser consideradas. Embora a produção adequada de muco cervical seja essencial para o transporte dos espermatozóides da vagina para a cavidade uterina, e tanto o canal vaginal quanto o colo do útero desempenham função importante como barreira à passagem dos espermatozóides, estes fatores recebem pouca atenção na investigação de casais com infertilidade inexplicada. Uma redução substancial do número de espermatozoides ocorre à medida que estes percorrem o trato reprodutivo feminino. Partindo de cerca de 200 a 300 milhões de espermatozoides depositados na vagina, apenas algumas centenas alcançam a proximidade do oócito. Alteracões do muco cervical podem rapidamente transformar o colo do útero num ambiente hostil, que em conjunto com alterações no ambiente vaginal e da estrutura de colo do útero, podem apresentar-se condicões impedientes para a concepção natural; desse modo, convertem-se em causa de infertilidade. Nesta revisão, discutimos o papel fisiológico do pH vaginal e do muco cervical na fertilidade, descrever várias condicões que podem tornar o muco cervical hostil aos espermatozoides e, por fim analisamos como estes fatores interferem na fisiopatologia da infertilidade inexplicada.

Bupropion treatment increases epididymal contractility and impairs sperm quality with no effects on the epididymal sperm transit time of male rats.

Bupropion is a dopamine (DA) and norepinephrine (NE) reuptake inhibitor used as smoking cessation and antidepressant drug with a lower incidence of male sexual dysfunction. We showed previously that sibutramine, a norepinephrine/serotonine reuptake inhibitor, reduced male rat fertility. As there are no studies evaluating the impact of bupropion treatment on spermatic parameters and male fertility, we evaluated the effects of bupropion treatment (15 and 30 mg kg(-1), 30 days) on sexual behavior, spermatic parameters and fertility of male Wistar rats and on the epididymal duct in vitro contractility. Bupropion 15 mg kg(-1) increased the serum luteinizing hormone level and the epididymal duct contractility, but the sperm quality was not affected. At 30 mg kg(-1) bupropion impaired sperm quality increasing the incidence of non-progressive sperm. The male sexual behavior and fertility were not modified at both bupropion doses. These results, in rats, suggest the importance of studies evaluating the effects of bupropion on the human male sperm quality.

Temporal changes in cervical mucus after insertion of the levonorgestrel-releasing intrauterine system.

BACKGROUND: The major contraceptive action of the levonorgestrel-releasing intrauterine system (LNG-IUS) is cervical mucus (CM) thickening, which prevents sperm penetration. No study to date has examined the temporal relationship between the insertion of the LNG-IUS and changes in CM quality and sperm penetration. STUDY DESIGN: Participants were enrolled in a clinically descriptive study to compare the quality of CM and three parameters of sperm penetration prior to insertion of the LNG-IUS and on Days 1, 3 and 5 after insertion. Measurements of estradiol, progesterone and levonorgestrel (LNG) in serum and LNG in CM were also carried out at these times. CM was analyzed using the World Health Organization CM grading criteria. Sperm penetration was determined using an in vitro sperm-CM penetration test. RESULTS: All 10 participants underwent LNG-IUS insertion during midcycle when CM quality was good and sperm penetration was excellent. On Day 1 after LNG-IUS insertion, the majority of participants demonstrated poor CM quality and poor sperm penetration. On Day 3, all participants had poor CM quality, and all but one subject had poor sperm penetration. By Day 5, all participants had poor CM quality and poor sperm penetration. LNG levels in CM peaked on the day after LNG-IUS insertion. CONCLUSION: Significant changes in quality of CM and sperm penetration were observed shortly after LNG-IUS insertion; however, CM can remain penetrable for up to 5 days when the LNG-IUS is inserted midcycle.

The use of prostaglandins in controlling estrous cycle of the ewe: a review.

This review considers the use of prostaglandin F(2α) and its synthetic analogues (PG) for controlling the estrous cycle of the ewe. Aspects such as phase of the estrus cycle, PG analogues, PG doses, ovarian follicle development pattern, CL formation, progesterone synthesis, ovulation rate, sperm transport, embryo quality, and fertility rates after PG administration are reviewed. Furthermore, protocols for estrus synchronization and their success in timed AI programs are discussed. Based on available information, the ovine CL is refractory to PG treatment for up to 2 days after ovulation. All PG analogues are effective when an appropriate dose is given; in that regard, there is a positive association between the dose administered and the proportion of ewes detected in estrus. Follicular response after PG is dependent on the phase of the estrous cycle at treatment. Altered sperm transport and low pregnancy rates are generally reported. However, reports on alteration of the steroidogenic capacity of preovulatory follicles, ovulation rate, embryo quality, recovery rates, and prolificacy, are controversial. Although various PG-based protocols can be used for estrus synchronization, a second PG injection improves estrus response when the stage of the estrous cycle at the first injection is unknown. The estrus cycle after PG administration has a normal length. Prostaglandin-based protocols for timed AI achieved poor reproductive outcomes, but increasing the interval between PG injections might increase pregnancy rates. Attempts to improve reproductive outcomes have been directed to provide a synchronized LH surge: use of different routes of AI (cervical or intrauterine), different PG doses, and increased intervals between PG injections. Finally we present our point of view regarding future perspectives on the use of PG in programs of controlled sheep reproduction.

Porcine sperm bind to specific 6-sialylated biantennary glycans to form the oviduct reservoir.

After mating, many female mammals store a subpopulation of sperm in the lower portion of the oviduct, forming a reservoir. The reservoir lengthens sperm lifespan, regulates sperm capacitation, controls polyspermy, and selects normal sperm. It is believed that sperm bind to glycans on the oviduct epithelium to form the reservoir, but the specific adhesion molecules that retain sperm are unclear. Herein, using a glycan array to test 377 glycans for their ability to bind porcine sperm, we found two glycan motifs in common among all glycans with sperm-binding ability: the Lewis X trisaccharide and biantennary structures containing a mannose core with 6-sialylated lactosamine at one or more termini. Binding to both motifs was specific; isomers of each motif did not bind sperm. Further work focused on sialylated lactosamine. Sialylated lactosamine was found abundantly on the apical side of epithelial cells collected from the oviduct isthmus, among N-linked and O-linked glycans. Sialylated lactosamine bound to the head of sperm, the region that interacts with the oviduct epithelium. After capacitation, sperm lost affinity for sialylated lactosamine. Receptor modification may contribute to release from the reservoir so that sperm can move to the site of fertilization. Sialylated lactosamine was required for sperm to bind oviduct cells. Simbucus nigra agglutinin or an antibody specific to sialylated lactosamine with a preference for Neu5Acalpha2-6Gal rather than Neu5Acalpha2-3Gal reduced sperm binding to oviduct isthmic cells, as did occupying putative receptors on sperm with sialylated biantennary glycans. These results demonstrate that sperm binding to oviduct 6-sialylated biantennary glycans is necessary for normal adhesion to the oviduct.

Morphological and morphometrical assessment of spermathecae of Aedes aegypti females

The vectorial capacity of Aedes aegypti is directly influenced by its high reproductive output. Nevertheless, females are restricted to a single mating event, sufficient to acquire enough sperm to fertilize a lifetime supply of eggs. How Ae. aegypti is able to maintain viable spermatozoa remains a mystery. Male spermatozoa are stored within either of two spermathecae that in Ae. aegypti consist of one large and two smaller organs each. In addition, each organ is divided into reservoir, duct and glandular portions. Many aspects of the morphology of the spermatheca in virgin and inseminated Ae. aegypti were investigated here using a combination of light, confocal, electron and scanning microscopes, as well as histochemistry. The abundance of mitochondria and microvilli in spermathecal gland cells is suggestive of a secretory role and results obtained from periodic acid Schiff assays of cell apexes and lumens indicate that gland cells produce and secrete neutral polysaccharides probably related to maintenance of spermatozoa. These new data contribute to our understanding of gamete maintenance in the spermathecae of Ae. aegypti and to an improved general understanding of mosquito reproductive biology.

Multifunctional glycoprotein DEFB126--a curious story of defensin-clad spermatozoa.

During maturation, the surface of mammalian spermatozoa undergoes dramatic changes leading to the acquisition of properties vital for survival and performance in the female reproductive tract. A prominent change is the addition to the sperm surface of an atypical ß-defensin polypeptide. In primates, the ß-defensin DEFB126 becomes adsorbed to the entire sperm surface as spermatozoa move through the epididymal duct. DEFB126 has a conserved ß-defensin core and a unique long glycosylated peptide tail. The carbohydrates of this domain contribute substantially to the sperm glycocalyx. DEFB126 is critical for efficient transport of sperm in the female reproductive tract, preventing their recognition by the female immune system, and might facilitate the delivery of capacitated sperm to the site of fertilization. A newly discovered dinucleotide deletion in the human DEFB126 gene is unusually common in diverse populations and results in a null allele. Predictably, men who are homozygous for the deletion produce sperm with an altered glycocalyx and impaired function, and have reduced fertility. Insights into the biology of DEFB126 are contributing to a better understanding of reproductive fitness in humans, as well as the development of diagnostics and therapeutics for male infertility.

[The structural basis for transport through the Fallopian tube]. / Struktúrny základ transportnej funkcie vajíckovodu.

The Fallopian tube has until recently been a neglected structure, bypassed by in vitro fertilization and seen only as a tube that transports the oocyte or early embryo to the uterus. More recently, its role is even more undervalued after the introduction of techniques of assisted reproduction, in which the Fallopian tubes become like unnecessary. The Fallopian tube performs several important functions. It captures the oocyte after ovulation, maintains and controls the migration of spermatozoa to the site of fertilization. It provides the special microenvironment for fertilization; nourishes the early embryo while it is being carried to the uterus and amplifies signals from embryo to the mother. In our article we conducted a systematic review of relevant articles found in PubMed, Scopus and ISI Web of Knowledge, focused on the new insights into the functional morphology of Fallopian tube. We described the possible function of muscle layer motility, ciliary activity and tubal fluid movement on transport of gamets / embryo, as well as we mentioned the negative factors (such as smoking, chlamydial infection or endometriosis) affecting the transport through the Fallopian tube.

Proteomics of cauda epididymal fluid from mature Holstein bulls.

The proteome of cauda epididymal fluid (CEF) from Holstein bulls was defined. Fluid was collected from the vas deferens, subjected to 2-D SDS-PAGE and spots identified by CapLC-MS/MS and MALDI-ToF/ToF. Because albumin accounted for 21.1% of all spot intensities in the gels examined by PDQuest, samples were subjected to albumin depletion and then analyzed again as before. Original CEF gels had 114 ± 3 spots, including as the most abundant: albumin, epididymal secretory protein E1, prostaglandin d-synthase and gelsolin. Epididymal fluid also expressed: clusterin, transferrin, N-acetyl-ß-glucosaminidase, cauxin, glutathione peroxidase, acidic seminal fluid protein (aSFP), aldehyde reductase, α-l-fucosidase, α-1-ß-glycoprotein, apolipoprotein A-1, ß actin, calmodulin, cathepsin D, cystatin E/M, enolase, galectin 3-binding protein, leucine amino-peptidase and nucleobindin. Albumin depletion decreased that very spot to 10% of its original intensity and the resulting gels had, on average, 137 ± 4 spots. Spots identified as dipeptidyl-peptidase 7, angiotensin-converting enzyme, arylsulfatase A, aspartylglucosaminidase, serine protease inhibitors, new isoforms of calmodulin, cystatin E/M and a 17-kDa nucleobindin appeared only in depleted maps. This study is the first to report nucleobindin and aSFP as epididymal components. We suggest that CEF proteins act to facilitate membrane remodeling, transport of lipophilic substances, protect sperm and prevent premature acrosome reaction.

Hormonal induction of spermiation, courting behavior and spawning in the southern bell frog, Litoria raniformis.

We trialled the efficacy of various exogenous hormones to induce spermiation, courtship behavior, and spawning in the "endangered" southern bell frog, Litoria raniformis. Intralymphatic administration of Lucrin(®), a synthetic nonapeptide luteinizing hormone releasing hormone (LHRH), was used successfully to induce courting behaviors and ejaculation of spermatozoa in males. Various hormones, including Lucrin(®), another synthetic LHRH analog ([des-Gly(10), D-Ala(6)]-LHRH), human chorionic gonadotropin, progesterone, and a dopamine receptor antagonist failed to promote oviposition and spawning in females. This and earlier studies indicate that in the efficacy of hormonal induction in amphibians varies between taxa, hormones, and genders. The lack of response in females may limit the use of reproduction technology in the southern bell frog and closely related species of Australian bell frogs.

Absence of estrogen receptor alpha leads to physiological alterations in the mouse epididymis and consequent defects in sperm function.

Male mice deficient in ESR1 (ERalpha) (Esr1KO mice) are infertile, and sperm recovered from the cauda epididymis exhibit reduced motility and fail to fertilize eggs in vitro. These effects on sperm appear to result from defective epididymal function and not a direct effect on spermatogenesis, as Esr1KO germ cells transplanted into wild-type testes yield normal offspring. We hypothesized that the previously described defect in efferent duct fluid reabsorption would lead to alterations in the epididymal fluid milieu, which would negatively impact sperm function. Analysis of the epididymal fluid revealed that the Esr1KO maintains a higher luminal pH throughout the epididymis, confirming an inability of the efferent ducts and/or epididymis to properly acidify the luminal contents. Subsequent studies showed that these abnormalities were not the result of global defects in epididymal function since protein secretion by the Esr1KO epididymis appeared normal as judged by SDS-PAGE of total secreted proteins and by immunoblotting of candidate secreted proteins. To gain insight into the basis of the aberrant fluid homeostasis in the Esr1KO epididymis, the expression of several enzymes and transporters known to be involved in acid/base regulation were analyzed. The levels of SLC9A3 (NHE3) as well as carbonic anhydrase XIV and SLC4A4 (NBC1) were all reduced in the proximal portion of the Esr1KO epididymis, while other components appeared unaffected, including other ion transporters and ATP6V0A1 (V-ATPase). The altered luminal milieu of the Esr1KO epididymis was shown to lead to a corresponding increase in the intracellular pH of Esr1KO sperm, relative to sperm from control animals. Since pH and bicarbonate ions are critical regulators of sperm cAMP levels and motility, we attempted to bypass the abnormal luminal and intracellular environment by supplementing sperm with exogenous cAMP. This treatment rescued all defective motility parameters, as assayed by CASA, further showing that motility defects are not intrinsic to the sperm but, rather, result from the abnormal epididymal milieu.

Disruption of the murine dynein light chain gene Tcte3-3 results in asthenozoospermia.

To elucidate the role of the mouse gene Tcte3 (Tctex2), which encodes a putative light chain of the outer dynein arm of cilia and sperm flagella, we have inactivated this gene in mice using targeted disruption. Breeding of heterozygous males and females resulted in normal litter size; however, we were not able to detect homozygous Tcte3-deficent mice using standard genotype techniques. In fact, our results indicate the presence of at least three highly similar copies of the Tcte3 gene (Tcte3-1, Tcte3-2, and Tcte3-3) in the murine genome. Therefore, quantitative real-time PCR was established to differentiate between mice having one or two targeted Tcte3-3 alleles. By this approach, Tcte3-3(-/-) animals were identified, which were viable and revealed no obvious malformation. Interestingly, some homozygous Tcte3-3-deficient male mice bred with wild-type female produced no offspring while other Tcte3-3-deficient males revealed decreased sperm motility but were fertile. In infertile Tcte3-3(-/-) males, spermatogenesis was affected and sperm motility was reduced, too, resulting in decreased ability of Tcte3-3-deficient spermatozoa to move from the uterus into the oviduct. Impaired flagellar motility is not correlated with any gross defects in the axonemal structure, since outer dynein arms are detectable in sperm of Tcte3-3(-/-) males. However, in infertile males, deficient Tcte3-3 function is correlated with increased apoptosis during male germ cell development, resulting in a reduction of sperm number. Moreover, multiple malformations in developing haploid germ cells are present. Our results support a role of Tcte3-3 in generation of sperm motility as well as in male germ cell differentiation.

Uterine mechanisms of ipsilateral directed spermatozoa transport: Evidence for a contribution of the utero-ovarian countercurrent system.

OBJECTIVE: Spermatozoa transport into uterus and fallopian tubes is directed to the side of the dominant follicle and seems to be controlled by the ipsilateral ovary. The objective of this study was to evaluate the temperature in the fallopian tubes as well as the concentrations of estradiol and progesterone in the utero-ovarian veins draining the ipsilateral ovary and compare these to the contralateral side of the uterus. STUDY DESIGN: A prospective clinical study. SETTING: Academic-assisted reproductive technology program. SUBJECTS: Temperature was measured in both oviducts of 10 patients each in the early phase as well as during the late follicular phase during the course of examination of tubal patency and function. Blood samples of the ovarian veins were obtained during hysterectomy in 10 premenopausal patients with regular menstrual cycles. Five of the women were in the early follicular phase and 5 were in the late follicular phase. RESULTS: Late follicular phase temperature as well as concentrations of estradiol and progesterone were significantly higher in the ipsilateral tube and the utero-ovarian veins draining the ipsilateral ovary as compared to the contralateral side. No such differences were found during the early follicular phase of the cycle. CONCLUSIONS: These data support our view that the uterus and fallopian tubes during the late follicular phase immediately before ovulation are composed of two functional units with different functional properties acting as a peristaltic pump resulting in increased transport of spermatozoa into the oviduct ipsilateral to the ovary bearing the dominant follicle and that this effect is mediated in part by the utero-ovarian countercurrent system.

The cystic fibrosis transmembrane conductance regulator in reproductive health and disease.

The cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel regulated by cAMP-dependent phosphorylation, which is expressed in epithelial cells of a wide variety of tissues including the reproductive tracts. Mutations in the gene encoding CFTR cause cystic fibrosis, a common genetic disease in Caucasian populations with a multitude of clinical manifestations including infertility/subfertility in both sexes. However, the physiological role of CFTR in reproduction and its involvement in the pathogenesis of reproductive diseases remain largely unknown. This review discusses the role of CFTR in regulating fluid volume and bicarbonate secretion in the reproductive tracts and their importance in various reproductive events. We also discuss the contribution of CFTR dysfunction to a number of pathological conditions. The evidence presented is consistent with an important role of CFTR in reproductive health and disease, suggesting that CFTR might be a potential target for the diagnosis and treatment of reproductive diseases including infertility.