Neonatal Genistein Exposure Permanently Disrupts Female Reproductive Tract Gene Expression and Tissue Architecture during Pregnancy.

AbstractFibroids (uterine leiomyomas) are the most common benign tumors of the female reproductive tract. Steroid hormones, growth factors, and cytokines have long been implicated in fibroid growth; however, research suggests that changes in the extracellular matrix and mechanical signaling play a critical role in fibroid growth and differentiation. Studies have shown that growth of fibroids is related to the change in the volume and composition of extracellular matrix with increased deposition of abnormal collagen, glycoproteins, laminins, fibronectins, and an increased osmotic stress. These changes generate mechanical stress which is converted to chemical signals in the cells through mechanotransduction and eventually affects gene expression and protein synthesis. Current studies also suggest that mechanical signaling in fibroid cells is abnormal as evidenced by decreased apoptosis of abnormal cells and deposition of a stiff extracellular matrix promoting fibrosis. Understanding and defining these mechanisms could help design new therapies for the treatment of fibroids.

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Drosophila female reproductive tract gene expression reveals coordinated mating responses and rapidly evolving tissue-specific genes

G3 Genes|Genome|Genetics ◽

10.1093/g3journal/jkab020 ◽

2021 ◽

Author(s):

Caitlin E McDonough-Goldstein ◽

Kirill Borziak ◽

Scott Pitnick ◽

Steve Dorus

Keyword(s):

Gene Expression ◽

Reproductive Tract ◽

Expression Profiles ◽

Female Reproductive Tract ◽

Tissue Specific ◽

Accelerated Evolution ◽

Before And After ◽

Complex Coordination ◽

Extracellular Environment

Abstract Sexual reproduction in internally fertilizing species requires complex coordination between female and male reproductive systems and among the diverse tissues of the female reproductive tract (FRT). Here, we report a comprehensive, tissue-specific investigation of Drosophila melanogaster FRT gene expression before and after mating. We identified expression profiles that distinguished each tissue, including major differences between tissues with glandular or primarily non-glandular epithelium. All tissues were enriched for distinct sets of genes possessing secretion signals and exhibiting accelerated evolution, as might be expected for genes participating in molecular interactions between the sexes within the FRT extracellular environment. Despite robust transcriptional differences between tissues, post-mating responses were dominated by coordinated transient changes indicative of an integrated systems-level functional response. This comprehensive characterization of gene expression throughout the FRT identifies putative female contributions to post-copulatory events critical to reproduction and potentially reproductive isolation, as well as the putative targets of sexual selection and conflict.

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Does the Act of Copulation per se, without Considering Seminal Deposition, Change the Expression of Genes in the Porcine Female Genital Tract?

International Journal of Molecular Sciences ◽

10.3390/ijms21155477 ◽

2020 ◽

Vol 21 (15) ◽

pp. 5477

Author(s):

Manuel Alvarez-Rodriguez ◽

Cristina A. Martinez ◽

Dominic Wright ◽

Heriberto Rodriguez-Martinez

Keyword(s):

Gene Expression ◽

Genital Tract ◽

Reproductive Tract ◽

Female Genital Tract ◽

Female Reproductive Tract ◽

Smooth Muscle Contractility ◽

Expression Of Genes ◽

Per Se ◽

Natural Mating ◽

Transcriptomic Changes

Semen—through its specific sperm and seminal plasma (SP) constituents—induces changes of gene expression in the internal genital tract of pigs, particularly in the functional sperm reservoir at the utero-tubal junction (UTJ). Although seminal effects are similarly elicited by artificial insemination (AI), major changes in gene expression are registered after natural mating, a fact suggesting the act of copulation induces per se changes in genes that AI does not affect. The present study explored which pathways were solely influenced by copulation, affecting the differential expression of genes (DEGs) of the pre/peri-ovulatory genital tract (cervix, distal uterus, proximal uterus and UTJ) of estrus sows, 24 h after various procedures were performed to compare natural mating with AI of semen (control 1), sperm-free SP harvested from the sperm-peak fraction (control 2), sperm-free SP harvested from the whole ejaculate (control 3) or saline-extender BTS (control 4), using a microarray chip (GeneChip® porcine gene 1.0 st array). Genes related to neuroendocrine responses (ADRA1, ADRA2, GABRB2, CACNB2), smooth muscle contractility (WNT7A), angiogenesis and vascular remodeling (poFUT1, NTN4) were, among others, overrepresented with distal and proximal uterine segments exhibiting the highest number of DEGs. The findings provide novel evidence that relevant transcriptomic changes in the porcine female reproductive tract occur in direct response to the specific act of copulation, being semen-independent.

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A non-genomic signaling pathway shut down by mating changes the estradiol-induced gene expression profile in the rat oviduct

Reproduction ◽

10.1530/rep-09-0218 ◽

2010 ◽

Vol 139 (3) ◽

pp. 631-644 ◽

Cited By ~ 9

Author(s):

Alexis Parada-Bustamante ◽

Pedro A Orihuela ◽

Mariana Ríos ◽

Catherina A Cuevas ◽

Maria Lorena Oróstica ◽

...

Keyword(s):

Gene Expression ◽

Signaling Pathway ◽

Gene Expression Profile ◽

Expression Profile ◽

Reproductive Tract ◽

Female Reproductive Tract ◽

Before And After ◽

Common Group ◽

Egg Transport ◽

Adenylyl Cyclase Inhibitor

Estradiol (E2) accelerates oviductal egg transport through intraoviductal non-genomic pathways in unmated rats and through genomic pathways in mated rats. This shift in pathways has been designated as intracellular path shifting (IPS), and represents a novel and hitherto unrecognized effect of mating on the female reproductive tract. We had reported previously that IPS involves shutting down the E2non-genomic pathway up- and downstream of 2-methoxyestradiol. Here, we evaluated whether IPS involves changes in the genomic pathway too. Using microarray analysis, we found that a common group of genes changed its expression in response to E2in unmated and mated rats, indicating that an E2genomic signaling pathway is present before and after mating; however, a group of genes decreased its expression only in mated rats and another group of genes increased its expression only in unmated rats. We evaluated the possibility that this difference is a consequence of an E2non-genomic signaling pathway present in unmated rats, but not in mated rats. Mating shuts down this E2non-genomic signaling pathway up- and downstream of cAMP production. TheStarlevel is increased by E2in unmated rats, but not in mated rats. This is blocked by the antagonist of estrogen receptor ICI 182 780, the adenylyl cyclase inhibitor SQ 22536, and the catechol-O-methyltransferase inhibitor, OR 486. These results indicate that the E2-induced gene expression profile in the rat oviduct differs before and after mating, and this difference is probably mediated by an E2non-genomic signaling pathway operating on gene expression only in unmated rats.

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The Xenoestrogen Bisphenol A Induces Growth, Differentiation, and c-fos Gene Expression in the Female Reproductive Tract*

Endocrinology ◽

10.1210/endo.139.6.6027 ◽

1998 ◽

Vol 139 (6) ◽

pp. 2741-2747 ◽

Cited By ~ 129

Author(s):

Rosemary Steinmetz ◽

Natasha A. Mitchner ◽

Andrea Grant ◽

Donald L. Allen ◽

Robert M. Bigsby ◽

...

Keyword(s):

Gene Expression ◽

Bisphenol A ◽

Reproductive Tract ◽

Female Reproductive Tract

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Experimental sexual selection reveals rapid divergence in male and female reproductive transcriptomes and their interactions

10.1101/2021.01.29.428831 ◽

2021 ◽

Author(s):

Paris Veltsos ◽

Damiano Porcelli ◽

Yongxiang Fang ◽

Andrew R. Cossins ◽

Michael G. Ritchie ◽

...

Keyword(s):

Gene Expression ◽

Sexual Selection ◽

Reproductive Tract ◽

Female Reproductive Tract ◽

Population Divergence ◽

Expression Divergence ◽

Male And Female ◽

Gene Expression Divergence ◽

Postcopulatory Sexual Selection ◽

Female Responses

AbstractMating causes substantial changes in females, altering male and female reproductive fitness. Some postmating effects are hypothesized to be at least partially mediated by gene expression changes, driven by postcopulatory sexual selection, which results in population divergence of reproductive proteins that could generate reproductive isolation. However, understanding of the direct role of sexual selection on gene expression divergence along with the subsequent molecular mismatches that could occur between diverging populations is limited. Here, we analyze gene expression divergence following over 150 generations of experimental evolution in which Drosophila pseudoobscura evolved under either elevated polyandry or enforced monogamy. We find that sexual selection rapidly impacted sex-, tissue-, and mating-specific responses, and not always in the predicted direction. Postmating female responses are either unique to each sexual selection treatment or exhibit asymmetric non-congruence, in which monogamy females upregulate and polyandry females downregulate the same genes following mating. This substantial population divergence of gene expression also gives rise to either unique or mismatched gene expression patterns in crosses between treatments. Many of these genes are involved in immune and stress responses, and non-congruent responses are particularly prevalent in the female reproductive tract, the main arena for postcopulatory sexual selection. In summary, we show that sexual selection has pervasive impacts on gene expression divergence acting both differentially between reproductive tissues of the same sex and asymmetrically in postmating female responses, and this divergence is highest in the female reproductive tract, the main arena for postcopulatory sexual selection.

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Spatiotemporal transcriptional dynamics of the cycling mouse oviduct

10.1101/2021.01.15.426867 ◽

2021 ◽

Author(s):

Elle C. Roberson ◽

Anna M. Battenhouse ◽

Riddhiman K. Garge ◽

Ngan Kim Tran ◽

Edward M. Marcotte ◽

...

Keyword(s):

Gene Expression ◽

Estrous Cycle ◽

Reproductive Tract ◽

Genetic Model ◽

Global Analysis ◽

Female Reproductive Tract ◽

Female Reproduction ◽

Anteroposterior Axis ◽

Transcriptional Dynamics ◽

Genomic Resource

AbstractFemale fertility in mammals requires iterative remodeling of the entire adult female reproductive tract across the menstrual/estrous cycle. However, while transcriptome dynamics across the estrous cycle have been reported in human and bovine models, no global analysis of gene expression across the estrous cycle has yet been reported for the mouse. Here, we examined the cellular composition and global transcriptional dynamics of the mouse oviduct along the anteroposterior axis and across the estrous cycle. We observed robust patterns of differential gene expression along the anteroposterior axis, but we found surprisingly few changes in gene expression across the estrous cycle. Notable gene expression differences along the anteroposterior axis included a surprising enrichment for genes related to embryonic development, such as Hox and Wnt genes. The relatively stable transcriptional dynamics across the estrous cycle differ markedly from other mammals, leading us to speculate that this is an evolutionarily derived state that may reflect the extremely rapid five-day mouse estrous cycle. This dataset fills a critical gap by providing an important genomic resource for a highly tractable genetic model of mammalian female reproduction.

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Characterization of a Porcine Model for Von Willebrand Disease Type 1 and 3 Regarding Expression of Angiogenic Mediators in the Nonpregnant Female Reproductive Tract

Comparative Medicine ◽

10.30802/aalas-cm-19-000003 ◽

2019 ◽

Vol 69 (5) ◽

pp. 401-412 ◽

Cited By ~ 1

Author(s):

Hanna Allerkamp ◽

Stefanie Lehner ◽

Mahnaz Ekhlasi-Hundrieser ◽

Carsten Detering ◽

Christiane Pfarrer ◽

...

Keyword(s):

Gene Expression ◽

Animal Model ◽

Growth Factor ◽

Reproductive Tract ◽

Porcine Model ◽

Angiogenic Factors ◽

Von Willebrand Disease ◽

Female Reproductive Tract ◽

Type 3 ◽

Von Willebrand

Von Willebrand disease (VWD), a blood coagulation disorder, is also known to cause angiodysplasia. Hitherto, no animal model has been found with angiodysplasia that can be studied in vivo. In addition, VWD patients tend to have a higher incidence of miscarriages for reasons unknown. Thus, we aimed to examine the influence of von Willebrand factor (VWF) on the female reproductive tract histology and the expression and distribution of angiogenic factors in a porcine model for VWD types 1 and 3. The disease-causing tandem duplication within the VWF gene occurred naturally in these pigs, making them a rare and valuable model. Reproductive organs of 6 animals (2 of each mutant genotype and 2 wildtype (WT) animals) were harvested. Genotype plus phenotype were confirmed. Several angiogenic factors were chosen for possible connections to VWF and analyzed alongside VWF by immunohistochemistry and quantitative gene expression studies. VWD type 3 animals showed angiodysplasia in the uterus and shifting of integrin αVβ3 from the apical membrane of uterine epithelium to the cytoplasm accompanied by increased vascular endothelial growth factor (VEGF) expression. Varying staining patterns for angiopoietin (Ang)-2 were observed among the genotypes. As compared with WT, the ovaries of the VWD type 3 animals showed decreased gene expression of ANG2 and increased gene expression of TIE (tyrosine kinase with immunoglobulin and epidermal growth factor homology domains) 2, with some differences in the ANG/TIE-system among the mutant genotypes. In conclusion, severely reduced VWF seems to evoke angiodysplasia in the porcine uterus. Varying distribution and expression of angiogenic factors suggest that this large animal model is promising for investigation of influence of VWF on angiogenesis in larger groups.

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Expression Profile of VEGF and VEGFR2 in the Female Reproductive Tract at the Time of Placentation in a Porcine Model of Von Willebrand Disease Type 1

Blood ◽

10.1182/blood-2018-99-112085 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3776-3776

Author(s):

Mario von Depka ◽

Mahnaz Ekhlasi-Hundrieser ◽

Carsten Detering ◽

Stefanie Lehner ◽

Christiane Pfarrer ◽

...

Keyword(s):

Gene Expression ◽

Early Pregnancy ◽

Reproductive Tract ◽

Porcine Model ◽

Conflicts Of Interest ◽

Von Willebrand Disease ◽

Female Reproductive Tract ◽

Von Willebrand

Abstract Objectives: Clinical studies showed that women affected by von Willebrand disease (VWD) trend towards higher rates of miscarriages, but the underlying pathomechanisms remain unclear. Several in vitro studies demonstrated an influence of von Willebrand factor (VWF) on angiogenesis, which seems to be partly mediated via VEGF. Since angiogenesis in the reproductive organs is essential to establish and maintain pregnancy, we aimed to investigate gene expression of VWF, VEGF, and its receptor VEGFR2 in non-pregnant and pregnant individuals, using a porcine model of VWD type 1. Methods: Tissue samples of uterus, oviduct and ovary were harvested from eight female pigs of which four were pregnant on day 30 (time of placentation) and four were non-pregnant and in estrus. Of each group, two were affected by VWD type 1 and two were wildtype (WT) individuals. The gene expression of VWF, VEGF, and VEGFR2 was measured by qRT-PCR and relatively quantified against the endothelial specific housekeeping genes PROCR and CD31 using the ΔΔCT method and calculating the respective x-fold changes. The gene expression differences were compared between both genotypes as well as between both reproductive states Mean differences were taken into account, if the divergences were consistent in both individuals of each group and not within the range of the group they were compared to. Results: Regarding the non-pregnant sows, VWF expression was lower in uterus and ovary of the VWD type 1 animals. This difference was not seen comparing the pregnant animals of each genotype, but the VWD type 1 animals showed higher VEGF expression in oviduct and higher VEGF and VEGFR2 expression in the ovary. The expression of VEGFR2 was reduced in the uterus. Comparing the non-pregnant with the pregnant animals within each genotype, the following results were found: the pregnant WT pigs showed increased expression of VEGFR2 in uterus and ovary, but decreased expression of VEGF in the uterus. For the pregnant VWD type 1 animals increased expression was found for VWF and VEGFR2 in the ovary, and decreased expression for VEGF in uterus and oviduct and VEGFR2 in the uterus. Discussion and Conclusion: Comparison of the different groups revealed differences of gene expression in the female reproductive tract during early pregnancy. The expectedly lower expression of VWF in the VWD type 1 animals was not found for the pregnant animals. Apparently, there is an increase of VWF levels during pregnancy as seen in women. While VEGFR2 expression in the uterus increases during placentation in the WT animals, it decreases in the VWD type 1 animals. This suggests altered regulation of early angiogenesis, which is essential during placentation. Expression of VEGF and VEGFR2 was increased in the ovaries of the VWD type 1 animals. This points to an enhanced involvement of this pathway during conversion of the ruptured follicles to sufficient corpora lutea graviditates, which may affect this process. Enhanced angiogenesis via the VEGF/VEGFR2-pathway due to lack of VWF was already shown in vitro. Our study shows that the expression of VEGF and VEGFR2 differs during early pregnancy in VWD type 1 compared to wildtype sows. Therefore, this pathway may influence angiogenesis in the reproductive tract. Disclosures No relevant conflicts of interest to declare.

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