Estrogens and prostaglandin F2α in the semen and blood plasma of stallions

Claus, R.; Dimmick, M.A.; Giménez, T.; Hudson, Lauren

doi:10.1016/0093-691x(92)90031-l

Cited by 53 publications

(32 citation statements)

References 15 publications

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“…While PGE is detectable in equine seminal plasma (Claus et al 1992 ), it is undetectable in rodent and porcine samples. In the human, extremely high levels of PGE are detected in seminal fl uid, with 300 μM of the 19-OH form detectable (Templeton et al 1978 ).…”

Section: Active Factors In Seminal Fluidmentioning

confidence: 86%

Seminal Fluid Signalling in the Female Reproductive Tract: Implications for Reproductive Success and Offspring Health

Schjenken

Robertson

2015

Advances in Experimental Medicine and Biology

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Carriage of sperm is not the only function of seminal fluid in mammals. Studies in mice show that at conception, seminal fluid interacts with the female reproductive tract to induce responses which influence whether or not pregnancy will occur, and to set in train effects that help shape subsequent fetal development. In particular, seminal fluid initiates female immune adaptation processes required to tolerate male transplantation antigens present in seminal fluid and inherited by the conceptus. A tolerogenic immune environment to facilitate pregnancy depends on regulatory T cells (Treg cells), which recognise male antigens and function to suppress inflammation and immune rejection responses. The female response to seminal fluid stimulates the generation of Treg cells that protect the conceptus from inflammatory damage, to support implantation and placental development. Seminal fluid also elicits molecular and cellular changes in the oviduct and endometrium that directly promote embryo development and implantation competence. The plasma fraction of seminal fluid plays a key role in this process with soluble factors, including TGFB, prostaglandin-E, and TLR4 ligands, demonstrated to contribute to the peri-conception immune environment. Recent studies show that conception in the absence of seminal plasma in mice impairs embryo development and alters fetal development to impact the phenotype of offspring, with adverse effects on adult metabolic function particularly in males. This review summarises our current understanding of the molecular responses to seminal fluid and how this contributes to the establishment of pregnancy, generation of an immune-regulatory environment and programming long-term offspring health.

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Section: Active Factors In Seminal Fluidmentioning

confidence: 86%

Seminal Fluid Signalling in the Female Reproductive Tract: Implications for Reproductive Success and Offspring Health

Schjenken

Robertson

2015

Advances in Experimental Medicine and Biology

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“…The identification of TLR4 as a key upstream regulator adds to our existing knowledge of TGFB as a major signaling factor in seminal fluid [21][22][23][24]. Other components in seminal fluid that are postulated to play a role in seminal fluid signaling include prostaglandins [45,46], IL8 [47], cysteine-rich secretory protein 3 [48], and in pig, porcine-sperm-adhesion proteins [49]. TLR4 has previously been identified to be expressed in the uterus of both mice [34] and human [50,51] as well as in the human cervix [52].…”

Section: Discussionmentioning

confidence: 98%

TLR4 Signaling Is a Major Mediator of the Female Tract Response to Seminal Fluid in Mice1

Schjenken

Glynn

Sharkey

et al. 2015

Biology of Reproduction

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Seminal fluid interacts with epithelial cells lining the female reproductive tract to induce expression of proinflammatory cytokines and chemokines, initiating immune tolerance mechanisms to facilitate pregnancy. TGFB cytokines are key signaling agents in seminal plasma but do not fully account for the female response to seminal fluid. We hypothesized that additional molecular pathways are utilized in seminal fluid signaling. Affymetrix microarray was employed to compare gene expression in the endometrium of mice 8 h after mating with either intact males or seminal fluid deficient (SVX/VAS) males. Bioinformatics analysis revealed TLR4 signaling as a strongly predicted upstream regulator activated by the differentially expressed genes and implicated TGFB signaling as a second key pathway. Quantitative PCR and microbead data confirmed that seminal fluid induces endometrial synthesis of several TLR4-regulated cytokines and chemokines, including CSF3, CXCL1, CXCL2, IL1A, IL6, LIF, and TNF. In primary uterine epithelial cells, CSF3, CXCL1, and CXCL2 were strongly induced by the TLR4 ligand LPS but suppressed by TGFB, while IL1A, TNF, and CSF2 were induced by both ligands. TLR4 was confirmed as essential for the full endometrial cytokine response using mice with a null mutation in Tlr4, where seminal fluid failed to induce endometrial Csf3, Cxcl2, Il6, and Tnf expression. This study provides evidence that TLR4 contributes to seminal fluid modulation of the periconception immune environment. Activation of TLR4 signaling by microbial or endogenous components of seminal fluid is thus implicated as a key element of the female tract response to seminal fluid at the outset of pregnancy in mice.

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“…However, the role that estrogen plays in male reproduction took several decades to appreciate. We now know that estrogen is produced in significant quantities in testes (i.e., rat rete testis fluid concentration is 248 6 95 pg/ml) [43], and is present in the semen of several species [43][44][45][46]. This is due to the presence of cytochrome P450 aromatase (CYP19A1), an enzyme that catalyzes the irreversible conversion of androgens into estrogens [47,48].…”

Section: Aromatasementioning

confidence: 97%

Estrogen, Efferent Ductules, and the Epididymis

Joseph¹,

Shur²,

Hess³

2010

Biology of Reproduction

117

106

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Estrogen's presence in the male reproductive system has been known for over 60 years, but its potential function in the epididymis remains an important area of investigation. Estrogen is synthesized by germ cells, producing a relatively high concentration in rete testis fluid. There are two estrogen receptors (ESR), the presence of which in the head of the epididymis is well documented and consistent between species; however, in other regions of the epididymis, their expression appears to be isotype, species, and cell specific. ESR1 is expressed constitutively in the epididymis; however, its presence is downregulated by high doses of estrogen, making the design of experiments complicated, as the phenotype of the Cyp19a1(-/-) mouse does not resemble that of the Esr1(-/-) mouse. Ligand-independent and DNA-binding Esr1 mutant models further demonstrate the complexity and importance of both signaling pathways in maintenance of efferent ductules and epididymis. Data now reveal the presence of not only classical nuclear receptors, but also cytoplasmic ESR and rapid responding membrane receptors; however, their importance in the epididymis remains undetermined. ESR1 regulates ion transport and water reabsorption in the efferent ducts and epididymis, and its regulation of other associated genes is continually being uncovered. In the male, some genes, such as Aqp9 and Slc9a3, contain both androgen and estrogen response elements and are dually regulated by these hormones. While estrogen pathways are a necessity for fertility in the male, future studies are needed to understand the interplay between androgens and estrogens in epididymal tissues, particularly in cell types that contain both receptors and their cofactors.

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Estrogens and prostaglandin F2α in the semen and blood plasma of stallions

Cited by 53 publications

References 15 publications

Seminal Fluid Signalling in the Female Reproductive Tract: Implications for Reproductive Success and Offspring Health

Seminal Fluid Signalling in the Female Reproductive Tract: Implications for Reproductive Success and Offspring Health

TLR4 Signaling Is a Major Mediator of the Female Tract Response to Seminal Fluid in Mice1

Estrogen, Efferent Ductules, and the Epididymis

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