scholarly journals The social shape of sperm: using an integrative machine-learning approach to examine sperm ultrastructure and collective motility

2021 ◽  
Vol 288 (1959) ◽  
pp. 20211553
Author(s):  
Kristin A. Hook ◽  
Qixin Yang ◽  
Leonard Campanello ◽  
Wolfgang Losert ◽  
Heidi S. Fisher
Keyword(s):  
Machine Learning ◽  
Reproductive Tract ◽  
Statistical Modelling ◽  
Cell Types ◽  
Equatorial Region ◽  
Sperm Head ◽  
Female Reproductive Tract ◽  
Aggregation Behaviour ◽  
Head Morphology

Sperm is one of the most morphologically diverse cell types in nature, yet they also exhibit remarkable behavioural variation, including the formation of collective groups of cells that swim together for motility or transport through the female reproductive tract. Here, we take advantage of natural variation in sperm traits observed across Peromyscus mice to test the hypothesis that the morphology of the sperm head influences their sperm aggregation behaviour. Using both manual and automated morphometric approaches to quantify their complex shapes, and then statistical modelling and machine learning to analyse their features, we show that the aspect ratio of the sperm head is the most distinguishing morphological trait and statistically associates with collective sperm movements obtained from in vitro observations. We then successfully use neural network analysis to predict the size of sperm aggregates from sperm head morphology and show that species with relatively wider sperm heads form larger aggregates, which is consistent with the theoretical prediction that an adhesive region around the equatorial region of the sperm head mediates these unique gametic interactions. Together these findings advance our understanding of how even subtle variation in sperm design can drive differences in sperm function and performance.

scholarly journals The social shape of sperm: Using an integrative machine-learning approach to examine sperm ultrastructure and collective motility

2020 ◽  
Author(s):  
Kristin A. Hook ◽  
Qixin Yang ◽  
Leonard Campanello ◽  
Wolfgang Losert ◽  
Heidi S. Fisher
Keyword(s):  
Machine Learning ◽  
Reproductive Tract ◽  
Cell Types ◽  
Equatorial Region ◽  
Sperm Head ◽  
Female Reproductive Tract ◽  
Machine Learning Approach ◽  
And Performance ◽  
Head Morphology

AbstractSperm are one of the most morphologically diverse cell types in nature, yet they also exhibit remarkable behavioral variation, including the formation of collective groups of cells that swim together for motility or transport through the female reproductive tract. Here we take advantage of the natural variation in sperm traits observed across Peromyscus mice to test the hypothesis that the morphology of the rodent sperm head influences their sperm aggregation behavior. Using machine learning and traditional morphometric approaches to quantify and analyze their complex shapes, we show that the elongation of the sperm head is the most distinguishing morphological trait in these rodents and, as predicted, significantly associates with collective sperm movements obtained from in vitro observations. We then successfully use neural network analysis to predict the size and proportion of sperm aggregates from sperm head morphology and show that species whose sperm feature relatively wider heads aggregate more often and form larger groups, providing support for the theoretical prediction that an adhesive region around the equatorial region of the sperm head mediates these unique gametic interactions. Together these findings advance our understanding of how even subtle variation in sperm design can drive differences in sperm function and performance.Subject AreasEvolution, Cellular Biology, Behavior

Development of parthenogenetic and fertilized mouse embryos in the uterus and in extra-uterine sites

Development ◽  
1975 ◽  
Vol 34 (2) ◽  
pp. 387-405
Author(s):  
S. A. Iles ◽  
M. W. McBurney ◽  
S. R. Bramwell ◽  
Z. A. Deussen ◽  
C. F. Graham
Keyword(s):  
Reproductive Tract ◽  
Neural Tissue ◽  
Cell Types ◽  
Mouse Embryos ◽  
Female Reproductive Tract ◽  
Embryonic Cells ◽  
Haploid Embryos ◽  
Keratinized Epithelium ◽  
Mouse Eggs

Mouse eggs were activated with hyaluronidase in vitro and subsequently transferred to the oviduct. In the female reproductive tract they formed morulae and blastocysts which died soon after implantation. Haploid blastocysts were transferred beneath the kidney capsule and here some formed disorganized egg-cylinder structures in a week. Morulae and blastocysts from haploid and diploid parthenogenones were also transferred beneath the testis capsule. Two to four months later the growths which had formed were sectioned. They contained neural tissue, pigment, keratinized epithelium, glandular epithelium, ciliated epithelium, cartilage, bone, muscle, adipose tissue, and haemopoietic tissue. The range of cell types was similar to that produced by fertilized control blastocysts except that the parthenogenones did not form identifiable yolk-sac carcinoma or embryonal carcinomacells. The growths from haploid and diploid parthenogenones in the testis were stained with Feulgen and their DNA content measured. Growths from diploid embryos contained the normal diploid amount of DNA while growths from haploid embryos contained less than this amount. Cell cultures were prepared from the growths. The cells which were investigated contained no Y chromosome, suggesting that they were derived from the embryonic cells rather than the cells of the male host. These cells contained a near diploid chromosome number, although some of them were originally derived from haploid embryos.

Simvastatin inhibits Wnt/β-catenin pathway in uterine leiomyoma

Endocrinology ◽  
2021 ◽  
Author(s):  
Malak El Sabeh ◽  
Subbroto Kumar Saha ◽  
Sadia Afrin ◽  
Mostafa A Borahay
Keyword(s):  
Uterine Leiomyoma ◽  
Reproductive Tract ◽  
Controlled Trial ◽  
Active Form ◽  
Cell Types ◽  
Female Reproductive Tract ◽  
Benign Tumors ◽  
Therapeutic Effects

Abstract The Wnt/β-catenin pathway is upregulated in uterine leiomyomas, the most common benign tumors in the female reproductive tract. Simvastatin is an anti-hyperlipidemic drug, and previous in vitro and in vivo reports showed it may have therapeutic effects in treating leiomyomas. The objective of this study is to examine the effects of simvastatin on the Wnt/β-catenin signaling pathway in leiomyoma. We treated primary and immortalized human leiomyoma cells with simvastatin and examined its effects using RT-qPCR, Western Blotting, and immunocytochemistry. We also examined the effects using human leiomyoma tissues from an ongoing, randomized controlled trial where women with symptomatic leiomyoma received simvastatin (40mg) or placebo for 3 months prior to their surgery. The results of this study reveal that simvastatin significantly reduced the expression of Wnt4 and its co-receptor LRP5. After simvastatin treatment, levels of total β-catenin and its active form, non-phosphorylated β-catenin, were reduced in both cell types. Additionally, simvastatin reduced the expression of Wnt4 and total β-catenin, as well as non-phosphorylated β-catenin protein expression in response to estrogen and progesterone. Simvastatin also inhibited the expression of c-Myc, a downstream target of the Wnt/β-catenin pathway. The effect of simvastatin on non-phosphorylated-β-catenin, the key regulator of the Wnt/β-catenin pathway, was recapitulated in human leiomyoma tissue. These results suggest that simvastatin may have a beneficial effect on uterine leiomyoma through suppressing the overactive Wnt/β-catenin pathway.

Head morphology of ram spermatozoa is associated with their ability to migrate in vitro and correlates with fertility

2016 ◽  
Vol 28 (11) ◽  
pp. 1825 ◽  
Author(s):  
Carmen Martínez-Rodríguez ◽  
Mercedes Alvarez ◽  
Elena López-Urueña ◽  
Susana Gomes-Alves ◽  
Luis Anel-López ◽  
...  
Keyword(s):  
Reproductive Tract ◽  
Relative Size ◽  
Principal Component ◽  
Female Reproductive Tract ◽  
Migration Test ◽  
Sperm Analysis ◽  
Mucus Barrier ◽  
Cell Subpopulations ◽  
Head Morphology

Fertility is a highly complex biological function that depends on several properties of spermatozoa that are necessary for them to overcome various barriers in the female reproductive tract to reach the fertilisation site. This ability has been evaluated in vitro using cervical mucus migration tests. Head morphology has been widely studied, and various studies have reported correlations between head morphology and motility, fertility and DNA fragmentation. In the present study, we first evaluated the relationship between the ability of ram spermatozoa to overcome the mucus surrogate barrier in an in vitro migration test and sperm head morphology. Sperm motility (determined by computer-aided sperm analysis) and the acrosomal status, viability and mitochondrial status (determined by flow cytometry) of control and migrating spermatozoa were assessed. Principal component analysis and clustering analysis of the values for the morphometric parameters assessed defined three cell subpopulations. One of these subpopulations, namely spermatozoa with a short and wide head, was absent from samples collected after conclusion of the migration test. Second, we evaluated relationships among head morphology characteristics, the ability to penetrate the artificial mucus and fertility. We did not find any correlation between fertility and the number of spermatozoa that migrated, whereas there was a negative correlation between the proportion of spermatozoa with a short and wide head in the fresh sperm sample and fertility. In conclusion, the head morphology of spermatozoa was associated with their ability to overcome a mucus barrier in a migration test, and the relative size of the non-migrating subpopulation was negatively related to male fertility.

ERK1/2 mediates sperm acrosome reaction through elevation of intracellular calcium concentration

Zygote ◽  
2014 ◽  
Vol 23 (5) ◽  
pp. 652-661 ◽  
Author(s):  
Yael Jaldety ◽  
Haim Breitbart
Keyword(s):  
Acrosome Reaction ◽  
Reproductive Tract ◽  
Egf Receptor ◽  
Direct Determination ◽  
Cell Types ◽  
Mek Inhibitor ◽  
Female Reproductive Tract ◽  
Ionophore A23187 ◽  
Intracellular Ca

SummaryMammalian sperm acquire fertilization capacity after residing in the female reproductive tract for a few hours in a process called capacitation. Only capacitated sperm can bind the zona pellucida (ZP) of the egg and undergo the acrosome reaction, a process that allows penetration and fertilization. Extracellular signal regulated kinase (ERK1/2) mediates signalling in many cell types, however its role in sperm function is largely unknown. Here we show that ERK1/2 is highly phosphorylated/activated after a short incubation of mouse sperm under capacitation conditions and that this phosphorylation is reduced after longer incubation. Further phosphorylation was observed upon addition of crude extract of egg ZP or epidermal growth factor (EGF). The mitogen-activated ERK-kinase (MEK) inhibitor U0126 abolished ERK1/2 phosphorylation, in vitro fertilization rate and the acrosome reaction induced by ZP or EGF but not by the Ca2+-ionophore A23187. Moreover, inhibition of ERK1/2 along the capacitation process diminished almost completely the sperm's ability to go through the acrosome reaction, while inhibition at the end of capacitation attenuated the acrosome reaction rate by only 45%. The fact that the acrosome reaction, induced by the Ca2+ -ionophore A23187, was not inhibited by U0126 suggests that ERK1/2 mediates the acrosome reaction by activating Ca2+ transport into the cell. Direct determination of intracellular [Ca2+] revealed that Ca2+ influx induced by EGF or ZP was completely blocked by U0126. Thus, it has been established that the increase in ERK1/2 phosphorylation/activation in response to ZP or by activation of the EGF receptor (EGFR) by EGF, is a key event for intracellular Ca2+ elevation and the subsequent occurrence of the acrosome reaction.

scholarly journals OVARIAN GRANULOSA CELLS FROM WOMEN WITH PCOS EXPRESS LOW LEVELS OF SARS-COV-2 RECEPTORS AND CO-FACTORS

2021 ◽  
Author(s):  
Aalaap Anand Naigaonkar ◽  
Krutika Madhukar Patil ◽  
Shaini Joseph ◽  
Indira Hinduja ◽  
Srabani Mukherjee
Keyword(s):  
Granulosa Cells ◽  
Reproductive Tract ◽  
Polycystic Ovary ◽  
Ovarian Follicle ◽  
Cell Types ◽  
Female Reproductive Tract ◽  
Vitro Fertilization ◽  
Ovarian Granulosa Cells ◽  
Lower Expression

Purpose: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is global pandemic with more than 3 million deaths so far. Female reproductive tract organs express coronavirus-associated receptors and factors (SCARFs); suggesting they may be susceptible to SARS-CoV-2 infection however the susceptibility of ovary/follicle/oocyte to the same is still elusive. Co-morbidities like obesity, type-2 diabetes mellitus, cardiovascular disease etc. increase the risk of SARS-CoV-2 infection. These features are common in women with polycystic ovary syndrome (PCOS), warranting further scope to study SCARFs expression in ovary of these women. Materials and methods: SCARFs expression in ovary and ovarian tissues of women with PCOS and healthy women was explored by analyzing publically available microarray datasets. Transcript expression of SCARFs were investigated in mural and cumulus granulosa cells (MGCs and CGCs) from control and PCOS women undergoing in vitro fertilization (IVF). Results: Microarray data revealed that ovary expresses all genes necessary for SARS-CoV-2 infection. PCOS women mostly showed down-regulated/unchanged levels of SCARFs. MGCs and CGCs from PCOS women showed lower expression of receptors ACE2, BSG and DPP4 and protease CTSB than in controls. MGCs showed lower expression of protease CTSL in PCOS than in controls. Expression of TMPRSS2 was not detected in both cell types. Conclusions: Human ovarian follicle may be susceptible to SARS-CoV-2 infection. Lower expression of SCARFs in PCOS indicate that the risk of SARS-CoV-2 infection to the ovary may be lesser in these women than controls. This knowledge may help in safe practices at IVF settings in the current pandemic. Keywords: SARS-CoV-2, COVID-19, Ovarian granulosa cells, Oocyte, PCOS, IVF

scholarly journals Organoids of the female reproductive tract

2021 ◽  
Vol 99 (4) ◽  
pp. 531-553 ◽  
Author(s):  
Cindrilla Chumduri ◽  
Margherita Y. Turco
Keyword(s):  
Reproductive Tract ◽  
Personalised Medicine ◽  
Three Dimensional ◽  
In Vitro Models ◽  
Experimental Models ◽  
Female Reproductive Tract ◽  
Cellular Heterogeneity ◽  
Dynamic Regulation ◽  
Pregnancy And Childbirth

AbstractHealthy functioning of the female reproductive tract (FRT) depends on balanced and dynamic regulation by hormones during the menstrual cycle, pregnancy and childbirth. The mucosal epithelial lining of different regions of the FRT—ovaries, fallopian tubes, uterus, cervix and vagina—facilitates the selective transport of gametes and successful transfer of the zygote to the uterus where it implants and pregnancy takes place. It also prevents pathogen entry. Recent developments in three-dimensional (3D) organoid systems from the FRT now provide crucial experimental models that recapitulate the cellular heterogeneity and physiological, anatomical and functional properties of the organ in vitro. In this review, we summarise the state of the art on organoids generated from different regions of the FRT. We discuss the potential applications of these powerful in vitro models to study normal physiology, fertility, infections, diseases, drug discovery and personalised medicine.

scholarly journals Spermatozoa Obtained From Alpaca vas deferens. Effects of Seminal Plasma Added at Post-thawing

2021 ◽  
Vol 8 ◽  
Author(s):  
Eduardo G. Aisen ◽  
Wilfredo Huanca López ◽  
Manuel G. Pérez Durand ◽  
Edita Torres Mamani ◽  
Juan C. Villanueva Mori ◽  
...  
Keyword(s):  
Seminal Plasma ◽  
Artificial Insemination ◽  
Reproductive Tract ◽  
Vas Deferens ◽  
Female Reproductive Tract ◽  
Low Fertility ◽  
Sperm Cells ◽  
South American Camelids ◽  
Thawing Process

The viscous seminal plasma (SP) is currently a major impediment to the handling of ejaculate and the development of some biotechnologies in South American camelids. The vas deferens-collected spermatozoa of alpacas is a useful technique to avoid this problem. On the other hand, SP contains a large protein component that has been implicated in the function of spermatozoa within the female reproductive tract. In this sense, the low fertility achieved using transcervical insemination with frozen-thawed spermatozoa in alpacas could be improved by adding SP. This study aimed to evaluate the effect of the whole SP on some in vitro parameters of alpaca spermatozoa after the freezing-thawing-process and the fertility after artificial insemination. It would contribute to a better understanding of the interaction between thawed sperm cells and SP. Spermatozoa were obtained by surgically diverted vas deferens. The samples were diluted with a Tris-based extender, packaged in straws, and frozen. At thawing, each straw was divided into two post-thawing conditions: with the addition of 10% of PBS (control) or with 10% SP (treatment). The sperm cells were evaluated using dynamic parameters, sperm cell morphology, and morphometry. Fertility was assessed by an artificial insemination trial. All in vitro parameters were analyzed by ANOVA. A heterogeneity test was scheduled for the fertility trial. After the freezing-thawing process, motility and plasma membrane functionality was improved when SP was added. No differences were found for post-thaw viability between the control and treatment samples. The percentage of normal cells was higher with SP at post-thawing, and a decrease of the presence of bent tailed spermatozoa with a droplet in the SP group was observed. The length of the head spermatozoa was 3.4% higher in the samples with PBS compared to those in which SP was added. Females pregnant at day 25 post-insemination were 0/12 (with SP inside the straw) and 1/10 (without SP inside the straw). In conclusion, the presence of 10% SP at post-thawing improves sperm cells' motility, functionality, and morphology, indicating that it would be beneficial to improve the frozen-thawed alpaca's physiology spermatozoa. More fertility trials must be developed to increase this knowledge.

Wnt-7a maintains appropriate uterine patterning during the development of the mouse female reproductive tract

Development ◽  
1998 ◽  
Vol 125 (16) ◽  
pp. 3201-3211 ◽  
Author(s):  
C. Miller ◽  
D.A. Sassoon
Keyword(s):  
Reproductive Tract ◽  
Hox Genes ◽  
Cell Types ◽  
Female Reproductive Tract ◽  
Molecular Characteristics ◽  
Anteroposterior Patterning ◽  
Stratified Epithelium ◽  
Distinct Cell ◽  
Hoxa Gene Expression ◽  
Posterior Shift

The murine female reproductive tract differentiates along the anteroposterior axis during postnatal development. This process is marked by the emergence of distinct cell types in the oviduct, uterus, cervix and vagina and is dependent upon specific mesenchymal-epithelial interactions as demonstrated by earlier heterografting experiments. Members of the Wnt family of signaling molecules have been recently identified in this system and an early functional role in reproductive tract development has been demonstrated. Mice were generated using ES-mediated homologous recombination for the Wnt-7a gene (Parr, B. A. and McMahon, A. P. (1995) Nature 374, 350–353). Since Wnt-7a is expressed in the female reproductive tract, we examined the developmental consequences of lack of Wnt-7a in the female reproductive tract. We observe that the oviduct lacks a clear demarcation from the anterior uterus, and acquires several cellular and molecular characteristics of the uterine horn. The uterus acquires cellular and molecular characteristics that represent an intermediate state between normal uterus and vagina. Normal vaginas have stratified epithelium and normal uteri have simple columnar epithelium, however, mutant uteri have stratified epithelium. Additionally, Wnt-7a mutant uteri do not form glands. The changes observed in the oviduct and uterus are accompanied by a postnatal loss of hoxa-10 and hoxa-11 expression, revealing that Wnt-7a is not required for early hoxa gene expression, but is required for maintenance of expression. These clustered hox genes have been shown to play a role in anteroposterior patterning in the female reproductive tract. In addition to this global posterior shift in the female reproductive tract, we note that the uterine smooth muscle is disorganized, indicating development along the radial axis is affected. Changes in the boundaries and levels of other Wnt genes are detectable at birth, prior to changes in morphologies. These results suggest that a mechanism whereby Wnt-7a signaling from the epithelium maintains the molecular and morphological boundaries of distinct cellular populations along the anteroposterior and radial axes of the female reproductive tract.

scholarly journals CatSperζ regulates the structural continuity of sperm Ca2+ signaling domains and is required for normal fertility

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Jean-Ju Chung ◽  
Kiyoshi Miki ◽  
Doory Kim ◽  
Sang-Hee Shim ◽  
Huanan F Shi ◽  
...  
Keyword(s):  
Reproductive Tract ◽  
Female Reproductive Tract ◽  
Targeted Disruption ◽  
Vitro Fertilization ◽  
Male Subfertility ◽  
Epididymal Spermatozoa ◽  
Mammalian Female ◽  
Signaling Domains

We report that the Gm7068 (CatSpere) and Tex40 (CatSperz) genes encode novel subunits of a 9-subunit CatSper ion channel complex. Targeted disruption of CatSperz reduces CatSper current and sperm rheotactic efficiency in mice, resulting in severe male subfertility. Normally distributed in linear quadrilateral nanodomains along the flagellum, the complex lacking CatSperζ is disrupted at ~0.8 μm intervals along the flagellum. This disruption renders the proximal flagellum inflexible and alters the 3D flagellar envelope, thus preventing sperm from reorienting against fluid flow in vitro and efficiently migrating in vivo. Ejaculated CatSperz-null sperm cells retrieved from the mated female uterus partially rescue in vitro fertilization (IVF) that failed with epididymal spermatozoa alone. Human CatSperε is quadrilaterally arranged along the flagella, similar to the CatSper complex in mouse sperm. We speculate that the newly identified CatSperζ subunit is a late evolutionary adaptation to maximize fertilization inside the mammalian female reproductive tract.

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