scholarly journals Follistatin is essential for normal postnatal development and function of mouse oviduct and uterus

2015 ◽  
Vol 27 (7) ◽  
pp. 985 ◽  
Author(s):  
S. J. Holdsworth-Carson ◽  
R. G. Craythorn ◽  
W. R. Winnall ◽  
K. Dhaliwal ◽  
R. Genovese ◽  
...  

Female mice lacking the follistatin gene but expressing a human follistatin-315 transgene (tghFST315) have reproductive abnormalities (reduced follicles, no corpora lutea and ovarian–uterine inflammation). We hypothesised that the absence of follistatin-288 causes the abnormal reproductive tract via both developmental abnormalities and abnormal ovarian activity. We characterised the morphology of oviducts and uteri in wild type (WT), tghFST315 and follistatin-knockout mice expressing human follistatin-288 (tghFST288). The oviducts and uteri were examined in postnatal Day-0 and adult mice (WT and tghFST315 only) using histology and immunohistochemistry. Adult WT and tghFST315 mice were ovariectomised and treated with vehicle, oestradiol-17β (100 ng injection, dissection 24 h later) or progesterone (1 mg × three daily injections, dissection 24 h later). No differences were observed in the oviducts or uteri at birth, but abnormalities developed by adulthood. Oviducts of tghFST315 mice failed to coil, the myometrium was disorganised, endometrial gland number was reduced and oviducts and uteri contained abundant leukocytes. After ovariectomy, tghFST315 mice had altered uterine cell proliferation, and inflammation was maintained and exacerbated by oestrogen. These studies show that follistatin is crucial to postnatal oviductal–uterine development and function. Further studies differentiating the role of ovarian versus oviductal–uterine follistatin in reproductive tract function at different developmental stages are warranted.

1999 ◽  
Vol 11 (3) ◽  
pp. 133 ◽  
Author(s):  
A. T. Mikhailov ◽  
M. Torrado

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.


Cells ◽  
2018 ◽  
Vol 7 (10) ◽  
pp. 153 ◽  
Author(s):  
Raquel Bernardino ◽  
David Carrageta ◽  
Ana Silva ◽  
Giuseppe Calamita ◽  
Marco Alves ◽  
...  

High 17β-Estradiol (E2) levels are known to cause alterations of spermatogenesis and environments throughout the male reproductive tract. Sertoli cells (SCs) ensure an adequate environment inside the seminiferous tubule. Glycerol stands as essential for the maintenance of blood–testis barrier created by SCs, however, the role of E2 in this process is not known. Herein, we hypothesized that the effect of E2 on glycerol permeability in mouse SCs (mSCs) could be mediated by aquaglyceroporins. The expression of aquaglyceroporins was assessed by RT-PCR and qRT-PCR. Glycerol permeability was evaluated by stopped-flow light scattering. We were able to identify the expression of AQP3 and AQP9 in mSCs where AQP9 is more abundant than AQP3. Our results show that high E2 levels decrease AQP9 mRNA abundance with no influence on AQP3 in mSCs. Interestingly, high E2 levels decreased mSCs’ permeability to glycerol, while downregulating AQP9 expression, thus suggesting a novel mechanism by which E2 modulates fluid secretion in the testis. In conclusion, E2 is an important regulator of mSCs physiology and secretion through changes in AQP9 expression and function. Thus, alterations in glycerol permeability induced by E2 may be the cause for male infertility in cases associated with the presence of high E2 levels.


Author(s):  
Weiyu Zhang ◽  
Fuquan Chen ◽  
Ruiqing Chen ◽  
Dan Xie ◽  
Jiao Yang ◽  
...  

AbstractEndogenous retroviruses (ERVs) contribute to ∼10 percent of the mouse genome. They are often silenced in differentiated somatic cells but differentially expressed at various embryonic developmental stages. A minority of mouse embryonic stem cells (ESCs), like 2-cell cleavage embryos, highly express ERV MERVL. However, the role of ERVs and mechanism of their activation in these cells are still poorly understood. In this study, we investigated the regulation and function of the stage-specific expressed ERVs, with a particular focus on the totipotency marker MT2/MERVL. We show that the transcription factor Zscan4c functions as an activator of MT2/MERVL and 2-cell/4-cell embryo genes. Zinc finger domains of Zscan4c play an important role in this process. In addition, Zscan4c interacts with MT2 and regulates MT2-nearby 2-cell/4-cell genes through promoting enhancer activity of MT2. Furthermore, MT2 activation is accompanied by enhanced H3K4me1, H3K27ac, and H3K14ac deposition on MT2. Zscan4c also interacts with GBAF chromatin remodelling complex through SCAN domain to further activate MT2 enhancer activity. Taken together, we delineate a previously unrecognized regulatory axis that Zscan4c interacts with and activates MT2/MERVL loci and their nearby genes through epigenetic regulation.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Daniela Welcker ◽  
Cornelia Stein ◽  
Natalia Martins Feitosa ◽  
Joy Armistead ◽  
Jin-Li Zhang ◽  
...  

AbstractThe extracellular matrix architecture is composed of supramolecular fibrillar networks that define tissue specific cellular microenvironments. Hemicentins (Hmcn1 and Hmcn2) are ancient and very large members (> 600 kDa) of the fibulin family, whose short members are known to guide proper morphology and functional behavior of specialized cell types predominantly in elastic tissues. However, the tissue distribution and function of Hemicentins within the cellular microenvironment of connective tissues has remained largely unknown. Performing in situ hybridization and immunofluorescence analyses, we found that mouse Hmcn1 and Hmcn2 show a complementary distribution throughout different tissues and developmental stages. In postnatal dermal–epidermal junctions (DEJ) and myotendinous junctions (MTJ), Hmcn1 is primarily produced by mesenchymal cells (fibroblasts, tenocytes), Hmcn2 by cells of epithelial origin (keratinocytes, myocytes). Hmcn1−/− mice are viable and show no overt phenotypes in tissue tensile strength and locomotion tests. However, transmission electron microscopy revealed ultrastructural basement membrane (BM) alterations at the DEJ and MTJ of Hmcn1−/− mice, pointing to a thus far unknown role of Hmcn1 for BM and connective tissue boundary integrity.


Reproduction ◽  
2012 ◽  
Vol 143 (5) ◽  
pp. 559-576 ◽  
Author(s):  
Warren B Nothnick

Proper development and function of the female reproductive tract are essential for successful reproduction. Regulation of the differentiated functions of the organs that make up the female reproductive tract is well established to occur at multiple levels including transcription, translation, and posttranslational modifications. Micro-RNA (miRNA)-mediated posttranscriptional gene regulation has emerged as a fundamental mechanism controlling normal tissue development and function. Emerging evidence indicates that miRNAs are expressed within the organs of the female reproductive tract where they function to regulate cellular pathways necessary for proper function of these organs. In this review, the functional significance of miRNAs in the development and function of the organs of the female reproductive tract is discussed. Initial discussion focuses on the role of miRNAs in the development of the organs of the female reproductive tract highlighting recent studies that clearly demonstrate that mice with disrupted Dicer1 expression are sterile, fail to develop uterine glands, and have muted estrogen responsiveness. Next, emphasis moves to discussion on our current knowledge on the characterization of miRNA expression in each of the organs of the female reproductive tract. When possible, information is presented and discussed with respect to regulation, function, and/or functional targets of these miRNA within each specific organ of the female reproductive tract.


1996 ◽  
Vol 8 (7) ◽  
pp. 1097 ◽  
Author(s):  
PD Zalewski ◽  
X Jian ◽  
LL Soon ◽  
WG Breed ◽  
RF Seamark ◽  
...  

The Zn(II)-specific fluorophore Zinquin was used to determine the regional distribution of free or loosely-bound Zn(II) in mouse spermatozoa. Spermatozoa from the testes exhibited bright fluorescence over the entire head; those from the caput epididymides generally fluoresced more brightly in the post-acrosomal region; and spermatozoa from the caudae epididymides fluoresced less brightly, with foci of fluorescence over the sperm head which were lost after extraction with Triton X-100 and hence appeared to be membrane-associated. Treatment of cauda sperm with sodium dodecyl sulfate resulted in a bright uniform Zinquin fluorescence in the heads, similar to that observed in caput sperm, indicating that the two types of sperm have similar amounts of head Zn(II) but that the availability of Zn(II) for binding Zinquin is different. By contrast, the intensity of tail fluorescence was similar in spermatozoa from different regions of the male reproductive tract and was largely unaffected by Triton X-100 extraction, consistent with an intracellular location. Similar differences were observed between caput sperm and cauda sperm in the rat. It is concluded that visualization and measurement of free or loosely-bound Zn(II) in subcellular compartments of spermatozoa should facilitate investigation of the role of this metal in the development and function of spermatozoa and abnormalities that might accompany infertility and Zn(II) deficiency.


2005 ◽  
Vol 17 (2) ◽  
pp. 246 ◽  
Author(s):  
G.V. Druery ◽  
M.D. Rival ◽  
D.A. Taggart ◽  
G.A. Shimmin ◽  
A.B. Horsup ◽  
...  

The southern hairy-nosed wombat (SHW), Lasiorhinus latifrons, is a model species in which to develop assisted breeding techniques for the endangered northern hairy-nosed wombat, Lasiorhinus krefftii. We recently showed that anoestrus SHW respond to eutherian gonadotrophins by production of multiple ovarian follicles, but ovulation had not occurred at the time of examination 24 h post-LH (Druery GV et al. 2003 Theriogenology 59, 391 abst). This study investigated the timing of ovulation in six anoestrus captive adult female SHW (n = 3 per group) after ovarian superstimulation using porcine FSH (200 mg total, Folltropin-V, Bioniche, Belleville, Ontario, Canada) administered s.c. at 12-h intervals over 7 days. Ovulation was triggered by a single s.c. dose of porcine LH (25 mg Lutropin-V, Bioniche) 12 h after the final FSH injection. Superstimulatory response was determined by laparoscopy immediately after the final FSH injection on Day 7 prior to LH. Group 1 was re-examined at 33, 36, and 39 h post-LH, and Group 2 at 42, 45, and 48 h post-LH, for evidence of ovulations using laparoscopy and transabdominal ultrasonography. Laparoscopy on Day 7 revealed an ovarian follicular response in all six females, which coincided with the highest levels of estradiol. The reproductive tract also responded to the treatment (swollen fimbriae and enlarged, highly vascular uteri). Multiple follicles (range 16–31) up to 11 mm in diameter were observed in five females. One female had ovulated, as determined by the presence of corpora lutea. Transabdominal ultrasonographic imaging was unable to confirm the number of follicles in stimulated ovaries. Ovulation had commenced by 36 h post-LH, with the majority occurring 39–45 h post-LH. Ovulation was recorded as having occurred if a dark red, highly vascular crater on the surface of the newly formed corpus hemorrhagicum was observed. Increased circulating levels of progesterone were confirmed 9 days after the last laparoscopies. These results have important implications for the development of assisted reproductive technologies in the SHW: (1) transabdominal ultrasound imaging is ineffective for determining ovarian activity; (2) laparoscopy is a well-tolerated, repeatable minor surgical procedure that can be used for intrauterine AI in this species in which nonsurgical AI is unlikely to succeed (Paris DBBP et al. 2003 Theriogenology 59, 401 abst); and (3) knowledge of the timing of ovulation will enable insemination of spermatozoa into the uterus prior to ovulation. Financial support was provided by Dr. M. Jacobson, and hormones were supplied by Bioniche.


Author(s):  
Rafał P. Piprek ◽  
Malgorzata Kloc ◽  
Paulina Mizia ◽  
Jacek Z. KUBIAK

Cadherins are a group of membrane proteins responsible for cell adhesion. They are crucial for cell sorting and recognition during the morphogenesis, but also play many other roles such as assuring tissue integrity and resistance to stretching, mechanotransduction, cell signaling, regulation of cell proliferation, apoptosis, survival, carcinogenesis, etc. Within the cadherin superfamily, the E- and N-cadherin have been especially well studied. They are involved in many aspects of sexual development and reproduction, such as germline development and gametogenesis, gonad development and functioning, and fertilization. E-cadherin is expressed in the primordial germ cells, (PGCs) and also participates in PGC migration to the developing gonads where they become enclosed by the N-cadherin-expressing somatic cells. The differential expression of cadherins is also responsible for the establishment of the testis or ovary structure. In the adult testes, the N-cadherin is responsible for the integrity of the seminiferous epithelium, regulation of sperm production, and the establishment of the blood-testis barrier. Sex hormones regulate the expression and turnover of N-cadherin influencing the course of spermatogenesis. In the adult ovaries, E- and N-cadherin assure the integrity of ovarian follicles and the formation of corpora lutea. Cadherins are expressed in the mature gametes, and facilitate the capacitation of sperm in the female reproductive tract, and gamete contact during fertilization. The germ cells and accompanying somatic cells express a series of different cadherins, however, their role in gonads and reproduction is still unknown. In this review, we show what is known and unknown about the role of cadherins in the germline and gonad development, and suggest the topics for future research.


PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249068
Author(s):  
Elena C. Sigmund ◽  
Lilian Baur ◽  
Philipp Schineis ◽  
Jorge Arasa ◽  
Victor Collado-Diaz ◽  
...  

Atypical chemokine receptor ACKR3 (formerly CXCR7) is a scavenging receptor that has recently been implicated in murine lymphatic development. Specifically, ACKR3-deficiency was shown to result in lymphatic hyperplasia and lymphedema, in addition to cardiac hyperplasia and cardiac valve defects leading to embryonic lethality. The lymphatic phenotype was attributed to a lymphatic endothelial cell (LEC)-intrinsic scavenging function of ACKR3 for the vascular peptide hormone adrenomedullin (AM), which is also important during postnatal lymphangiogenesis. In this study, we investigated the expression of ACKR3 in the lymphatic vasculature of adult mice and its function in postnatal lymphatic development and function. We show that ACKR3 is widely expressed in mature lymphatics and that it exerts chemokine-scavenging activity in cultured murine skin-derived LECs. To investigate the role of LEC-expressed ACKR3 in postnatal lymphangiogenesis and function during adulthood, we generated and validated a lymphatic-specific, inducible ACKR3 knockout mouse. Surprisingly, in contrast to the reported involvement of ACKR3 in lymphatic development, our analyses revealed no contribution of LEC-expressed ACKR3 to postnatal lymphangiogenesis, lymphatic morphology and drainage function.


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