Expression Patterns of Mouse Follistatin Variants Fst288 and Fst315, Fstl3, Activin A and Its Receptors and the Inhibin Subunits, Throughout the Male Mouse Reproductive Tract.

Activin A and its inhibitors follistatin and inhibin play key roles in development and function of the male reproductive tract. Quantitative (q) polymerase chain reaction (PCR) was used to evaluate the expression of Inhba (the gene encoding activin A subunits), Inha and Inhbb (genes encoding the inhibin B subunits), as well as the genes for follistatin (Fst) and follistatin-like 3 (Fstl3) and the activin receptor subunits, in the male mouse reproductive tract. A qPCR assay that discriminated between the two follistatin variants of Fst288 (tissue-bound form) and Fst315 (circulating) was established. Activin A protein was measured by ELISA, whereas the inhibin α-subunit and total follistatin proteins were measured by radioimmunoassay (RIA). A screen of 22 tissues demonstrated tissue-specific regulation of the follistatin variants, with Fst288 highly expressed in the vas deferens and Fst315 most highly expressed in the skin. The expression of Fst288 and Fst315 and follistatin protein levels increased progressively from the testis through to the distal vas deferens. Inhba and the activin receptors were highly expressed in the epididymis, but activin A protein was elevated in both the epididymis and vas deferens. Inhibin α-subunit mRNA and protein and Inhbb expression were highest in the testis. These results indicate a role for activin A within the epididymis, but also that activin A bioactivity may be increasingly inhibited by follistatin distally along the male reproductive tract.

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Carboxylesterase overexpression in the male reproductive tract: a universal safeguarding mechanism?

Reproduction Fertility and Development ◽

10.1071/rd99011 ◽

1999 ◽

Vol 11 (3) ◽

pp. 133 ◽

Cited By ~ 16

Author(s):

A. T. Mikhailov ◽

M. Torrado

Keyword(s):

Reproductive Tract ◽

Expression Patterns ◽

Cell Lineage ◽

Environmental Chemicals ◽

Male Reproductive Tract ◽

Morphological Organization ◽

Associated Functions ◽

And Function ◽

Hypothetical Explanation

Data on expression patterns of carboxylesterases in the male reproductive tract of different animal groups (i.e. bivalve mollusks, fruitflies and rodents) are summarized to highlight some particularly interesting questions in the context of sperm differentiation, maturation and function. The male reproduc-tive system, in spite of extreme variation in the anatomical/morphological organization in different species, is characterized by similar patterns of male-dependent carboxylesterase overexpression. The phenomenon of conserved carboxylesterase overexpression indicates similar male sex-associated functions of the enzymes. There is possible evidence of carboxylesterase recruitment by male reproductive-tract tissues indi-cating that it could be adaptive for spermatogenesis, sperm maturation and sperm use. Moreover, this idea can be extended to include a sperm cell lineage protection. This issue is discussed in the light of recent data on environmental reproductive xenobiotics that can provide a basis for a hypothetical explanation of car-boxylesterase overexpression in the male reproductive tract. Based on a well-known role of car-boxylesterases in detoxification of environmental chemicals such as organophosphate pesticides, it is proposed that various male genital tract carboxylesterases may be characterized by a similar physiological function to protect the male reproductive system against xenobiotic influences that could provoke its dys-function, thus altering sperm differentiation and maturation.

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Genistein exerts estrogen-like effects in male mouse reproductive tract

Molecular and Cellular Endocrinology ◽

10.1016/s0303-7207(98)00152-x ◽

1998 ◽

Vol 144 (1-2) ◽

pp. 83-93 ◽

Cited By ~ 76

Author(s):

L Strauss ◽

S Mäkelä ◽

S Joshi ◽

I Huhtaniemi ◽

R Santti

Keyword(s):

Male Mouse ◽

Reproductive Tract

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308. FOLLISTATIN SPLICE VARIANTS FST288 AND FST315 INCREASE DURING EARLY MOUSE PREGNANCY: REGULATION BY PROGESTERONE?

Reproduction Fertility and Development ◽

10.1071/srb10abs308 ◽

2010 ◽

Vol 22 (9) ◽

pp. 108

Author(s):

R. G. Craythorn ◽

W. R. Winnall ◽

M. P. Hedger ◽

P. A. W. Rogers ◽

D. M. De Kretser ◽

...

Keyword(s):

Mrna Expression ◽

Early Pregnancy ◽

Reproductive Tract ◽

Splice Variants ◽

Heparan Sulphate ◽

Activin A ◽

Female Reproductive Tract ◽

Mouse Uterus ◽

Rate Of Increase ◽

Exogenous Progesterone

Follistatin acts by binding and neutralising the activity of activin-A, which has important regulatory roles in development, reproduction and inflammation. There are two isoforms of follistatin comprising 288 and 315 amino acids (FST288 and FST315), resulting from alternative gene splicing. FST288 binds spontaneously to heparan sulphate and is largely bound to cell surface proteoglycans. FST315 is the predominant circulating form and can only bind to heparan sulphate after binding activin-A. The regulation of these splice variants in the female reproductive tract have not been investigated in detail. In this study, our aim was to quantify the expression of FST288 and FST315 mRNA in the mouse uterus during early pregnancy (days 1–4, pre-implantation), and in response to exogenous oestradiol-17b (100 ng × single s.c. injection, dissection after 24 h) and progesterone (1 mg × three daily s.c. injections, dissection 24 h after last injection) in ovariectomised mice. Gene expression was analysed using quantitative RT-PCR. Primers amplifying a product from exon 5 to 6a (unique to FST288) or from exon 5 to 6b (unique to FST315) were used to discriminate the isoforms. In early pregnancy, expression of both FST288 and FST315 increased significantly (approximately 35-fold and 100-fold, respectively) on days 3–5, relative to days 1–2, corresponding with the increase in circulating progesterone levels that occurs at day 3. A significant increase in FST288 and FST315 mRNA expression (both approximately 35-fold) was also observed in ovariectomised mice in response to exogenous progesterone, but there was no increase in response to oestradiol-17β. In contrast to the similar rate of increase in response to exogenous progesterone, FST315 mRNA expression increased more rapidly than FS288 in early pregnancy, indicating that differential regulation of the two isoforms also occurs. We conclude that progesterone regulates both FST288 and FST315 mRNA expression during early pregnancy in the mouse uterus.

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Absence of relaxin immunostaining in the male reproductive tracts of the rat and mouse.

Journal of Histochemistry & Cytochemistry ◽

10.1177/34.7.3519757 ◽

1986 ◽

Vol 34 (7) ◽

pp. 945-948 ◽

Cited By ~ 9

Author(s):

M B Anderson ◽

M Collado-Torres ◽

M R Vaupel

Keyword(s):

Reproductive System ◽

Male Mouse ◽

Reproductive Tract ◽

Seminal Vesicles ◽

Immunohistochemical Method ◽

Primary Antiserum ◽

Homologous Antiserum ◽

Immunohistochemical Studies

By use of the biotin-avidin immunohistochemical method and a homologous antiserum as the primary antiserum, relaxin immunostaining was absent in the testes, prostate, seminal vesicles, and epididymides of the rat. Relaxin immunostaining was also lacking when anti-porcine relaxin serum was employed as the primary antiserum. Furthermore, immunohistochemical studies for relaxin localization in the reproductive tract of the male mouse using both anti-rat and anti-porcine relaxin sera also revealed an absence of the hormone in the reproductive system of this species. Although this study suggests that immunoreactive relaxin is absent in the male reproductive tracts of both the rat and mouse, it raises some questions concerning the reports in the literature of the presence of relaxin-like substances in the male reproductive tracts of other species. These reports are discussed in relation to our current results.

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Similarities and differences in uterine gene expression patterns caused by treatment with physiological and non-physiological estrogens

Journal of Molecular Endocrinology ◽

10.1677/jme.0.0310487 ◽

2003 ◽

Vol 31 (3) ◽

pp. 487-497 ◽

Cited By ~ 30

Author(s):

H Watanabe ◽

A Suzuki ◽

M Kobayashi ◽

DB Lubahn ◽

H Handa ◽

...

Keyword(s):

Gene Expression ◽

Estrogen Receptor ◽

Reproductive Tract ◽

Stress Proteins ◽

Expression Patterns ◽

Gene Expression Patterns ◽

Response Patterns ◽

Genes Encoding ◽

The Many ◽

Dose Responses

Administration of physiological and non-physiological estrogens during pregnancy or after birth is known to have adverse effects on the development of the reproductive tract and other organs. Although it is believed that both estrogens have similar effects on gene expression, this view has not been tested systematically. To compare the effects of physiological (estradiol; E2) and non-physiological (diethylstilbestrol; DES) estrogens, we used DNA microarray analysis to examine the uterine gene expression patterns induced by the two estrogens. Although E2 and DES induced many genes to respond in the same way, different groups of genes showed varying levels of maximal activities to each estrogen, resulting in different dose-response patterns. Thus, each estrogen has a distinct effect on uterine gene expression. The genes were classified into clusters according to their dose-responses to the two estrogens. Of the eight clusters, only two correlated well with the uterotropic effect of different doses of E2. One of these clusters contained genes that were upregulated by E2, which included genes encoding several stress proteins and transcription factors. The other cluster contained genes that were downregulated by E2, including genes related to metabolism, transcription and detoxification processes. The expression of these genes in estrogen receptor-deficient mice was not affected by E2 treatment, indicating that these genes are affected by the E2-bound estrogen receptor. Thus, of the many genes that are affected by estrogen, it was suggested that only a small number are directly involved in the uterotropic effects of estrogen treatment.

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Genomic and transcriptomic investigations of the evolutionary transition from oviparity to viviparity

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1816086116 ◽

2019 ◽

Vol 116 (9) ◽

pp. 3646-3655 ◽

Cited By ~ 7

Author(s):

Wei Gao ◽

Yan-Bo Sun ◽

Wei-Wei Zhou ◽

Zi-Jun Xiong ◽

Luonan Chen ◽

...

Keyword(s):

Reproductive Tract ◽

Expression Patterns ◽

Amino Acid Replacement ◽

Egg Laying ◽

Female Reproductive Tract ◽

Evolutionary Transition ◽

Placental Development ◽

Squamate Reptiles ◽

Low Levels ◽

Parity Mode

Viviparous (live-bearing) vertebrates have evolved repeatedly within otherwise oviparous (egg-laying) clades. Over two-thirds of these changes in vertebrate reproductive parity mode happened in squamate reptiles, where the transition has happened between 98 and 129 times. The transition from oviparity to viviparity requires numerous physiological, morphological, and immunological changes to the female reproductive tract, including eggshell reduction, delayed oviposition, placental development for supply of water and nutrition to the embryo by the mother, enhanced gas exchange, and suppression of maternal immune rejection of the embryo. We performed genomic and transcriptomic analyses of a closely related oviparous–viviparous pair of lizards (Phrynocephalus przewalskii and Phrynocephalus vlangalii) to examine these transitions. Expression patterns of maternal oviduct through reproductive development of the egg and embryo differ markedly between the two species. We found changes in expression patterns of appropriate genes that account for each of the major aspects of the oviparity to viviparity transition. In addition, we compared the gene sequences in transcriptomes of four oviparous–viviparous pairs of lizards in different genera (Phrynocephalus, Eremias, Scincella, and Sphenomorphus) to look for possible gene convergence at the sequence level. We discovered low levels of convergence in both amino acid replacement and evolutionary rate shift. This suggests that most of the changes that produce the oviparity–viviparity transition are changes in gene expression, so occasional reversals to oviparity from viviparity may not be as difficult to achieve as has been previously suggested.

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Follistatin and activin A production by the male reproductive tract

Human Reproduction ◽

10.1093/humrep/13.12.3319 ◽

1998 ◽

Vol 13 (12) ◽

pp. 3319-3325 ◽

Cited By ~ 28

Author(s):

R. A. Anderson ◽

L. W. Evans ◽

D. S. Irvine ◽

M. A. McIntyre ◽

N. P. Groome ◽

...

Keyword(s):

Reproductive Tract ◽

Activin A ◽

Male Reproductive Tract

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1395: Presence in Mice and Men of a Novel Class of Leukocyte/Macrophages Essential Fornormal Development of Male Mouse Reproductive Tract

The Journal of Urology ◽

10.1016/s0022-5347(18)38620-8 ◽

2004 ◽

Vol 171 (4S) ◽

pp. 367-367

Author(s):

Robert C. Eyre ◽

Thomas E. Mullen ◽

Rachel L. Kiessling ◽

Ann A. Kiessling

Keyword(s):

Male Mouse ◽

Reproductive Tract

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SIX1 cooperates with RUNX1 and SMAD4 in cell fate commitment of Müllerian duct epithelium

Cell Death and Differentiation ◽

10.1038/s41418-020-0579-z ◽

2020 ◽

Vol 27 (12) ◽

pp. 3307-3320

Author(s):

Jumpei Terakawa ◽

Vanida A. Serna ◽

Devi M. Nair ◽

Shigeru Sato ◽

Kiyoshi Kawakami ◽

...

Keyword(s):

Transcription Factor ◽

Cell Fate ◽

Reproductive Tract ◽

Critical Role ◽

Activin A ◽

Genetically Engineered ◽

Mitogen Activated Protein Kinase ◽

Mullerian Duct ◽

Müllerian Duct ◽

Duct Epithelium

AbstractDuring female mammal reproductive tract development, epithelial cells of the lower Müllerian duct are committed to become stratified squamous epithelium of the vagina and ectocervix, when the expression of ΔNp63 transcription factor is induced by mesenchymal cells. The absence of ΔNp63 expression leads to adenosis, the putative precursor of vaginal adenocarcinoma. Our previous studies with genetically engineered mouse models have established that fibroblast growth factor (FGF)/mitogen-activated protein kinase (MAPK), bone morphogenetic protein (BMP)/SMAD, and activin A/runt-related transcription factor 1 (RUNX1) signaling pathways are independently required for ΔNp63 expression in Müllerian duct epithelium (MDE). Here, we report that sine oculis homeobox homolog 1 (SIX1) plays a critical role in the activation of ΔNp63 locus in MDE as a downstream transcription factor of mesenchymal signals. In the developing mouse reproductive tract, SIX1 expression was restricted to MDE within the future cervix and vagina. SIX1 expression was totally absent in SMAD4 null MDE and was reduced in RUNX1 null and FGFR2 null MDE, indicating that SIX1 is under the control of vaginal mesenchymal factors: BMP4, activin A and FGF7/10. Furthermore, Six1, Runx1, and Smad4 gene-dose-dependently activated ΔNp63 expression in MDE within the vaginal fornix. Using a mouse model of diethylstilbestrol (DES)-associated vaginal adenosis, we found DES action through epithelial estrogen receptor α (ESR1) inhibits activation of ΔNp63 locus in MDE by transcriptionally repressing SIX1 and RUNX1 in the vaginal fornix.

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