scholarly journals Differences in oocyte development and estradiol sensitivity among mouse strains

Reproduction ◽  
2010 ◽  
Vol 139 (2) ◽  
pp. 349-357 ◽  
Author(s):  
Melissa E Pepling ◽  
Emily A Sundman ◽  
Nicole L Patterson ◽  
Grant W Gephardt ◽  
Leonard Medico ◽  
...  

Mouse oocytes develop in clusters of interconnected cells called germline cysts. Shortly after birth, the majority of cysts break apart and primordial follicles form, consisting of one oocyte surrounded by granulosa cells. Concurrently, oocyte number is reduced by two-thirds. Exposure of neonatal females to estrogenic compounds causes multiple oocyte follicles that are likely germline cysts that did not break down. Supporting this idea, estrogen disrupts cyst breakdown and may regulate normal oocyte development. Previously, the CD-1 strain was used to study cyst breakdown and oocyte survival, but it is unknown if there are differences in these processes in other mouse strains. It is also unknown if there are variations in estrogen sensitivity during oocyte development. Here, we examined neonatal oocyte development in FVB, C57BL/6, and F2 hybrid (Oct4-GFP) strains, and compared them with the CD-1 strain. We found variability in oocyte development among the four strains. We also investigated estrogen sensitivity differences, and found that C57BL/6 ovaries are more sensitive to estradiol than CD-1, FVB, or Oct4-GFP ovaries. Insight into differences in oocyte development will facilitate comparison of mice generated on different genetic backgrounds. Understanding variations in estrogen sensitivity will lead to better understanding of the risks of environmental estrogen exposure in humans.

Development ◽  
2021 ◽  
pp. dev.197459
Author(s):  
Ren Tanimoto ◽  
Kiyono Sekii ◽  
Kanako Morohaku ◽  
Jianzhen Li ◽  
David Pepin ◽  
...  

In mammals, primordial follicles assembled in fetuses or during infancy constitute the oocyte resources for life. Exposure to 17beta-estradiol and phytogenic or endocrine-disrupting chemicals during pregnancy and/or the perinatal period leads to the failure of normal follicle formation. However, the mechanisms underlying estrogen-mediated abnormal follicle formation and physiological follicle formation in the presence of endogenous natural estrogen are not well-understood. Here, we reveal that estrogen receptor 1, activated by estrogen, binds to the 5′ region of the anti-Mullerian hormone (Amh) gene and upregulates its transcription before follicle formation in cultured mouse fetal ovaries. Ectopic expression of AMH protein was observed in pregranulosa cells of these explants. Furthermore, AMH addition to the culture medium inhibited normal follicle formation. Conversely, alpha-fetoprotein (AFP) produced in fetal liver reportedly blocks estrogen action, although its role in follicle formation is unclear. We further demonstrated that AFP addition to the medium inhibited ectopic AMH expression via estrogen, leading to successful follicle formation in vitro. Collectively, our in vitro experiments suggest that upon estrogen exposure, the integrity of follicle assembly in vivo is ensured by AFP.


Reproduction ◽  
2000 ◽  
pp. 43-48 ◽  
Author(s):  
S Meredith ◽  
G Dudenhoeffer ◽  
K Jackson

In the present study, follicles were classified according to the morphology of their granulosa cells. Type B follicles contained only flattened granulosa cells; type B/C follicles had a mixture of flattened and cuboidal granulosa cells in a single layer, and type C follicles had a single layer of cuboidal granulosa cells. The primary objectives of the study were to determine whether 5-bromo-2-deoxyuridine incorporation into type B/C follicles was a marker for initiation of growth and how long type B/C follicles could remain at the same stage before transformation to type C follicles. Female Holtzman rats received bromo-deoxyuridine for 7 days. After the infusion (day minipumps were removed = day 0), rats were ovariectomized on days 0 (n = 9), 30 (n = 8), 90 (n = 8) and 150 (n = 9). The numbers of type B, B/C and C follicles within one ovary were determined using modified fractionator counting. Analysis over all times demonstrated that there were more (P < 0.0001) type B/C (941 +/- 61 per ovary) than type C (140 +/- 18 per ovary) or type B (159 +/- 19 per ovary) follicles. The numbers of type B and type C follicles did not differ from each other at any time. Only one of 34 rats evaluated had bromo-deoxyuridine-labelled type B follicles. On day 150, 57% of the bromo-deoxyuridine-labelled type B/C follicles remained from day 0. It is concluded that (1) DNA synthesis in granulosa cells of type B/C follicles is not a reliable indicator of impending growth; and (2) type B and type B/C follicles are both components of the pool of primordial follicles.


Parasitology ◽  
1984 ◽  
Vol 88 (4) ◽  
pp. 665-675
Author(s):  
J.G. Howard

The following brief survey considers various manoeuvres which can be applied to manipulate the immune response to parasitic infectionsin vivo. The examples quoted largely concern malaria, babesiosis, schistosomiasis and leishmaniasis, predominantly in inbred mouse strains. Since my own relevant research experience has been restricted to leishmaniasis, this will receive undue emphasis, although it does illustrate particularly well points I wish to stress. The types of intervention described do not all provide the precision of interpretation with which they are sometimes credited. Thus, effects of immunosuppression or T-cell depletion alone can usually only implicate the specific immune response (in its broad sense) in shaping the natural history and outcome of an infection or in underlying the effect of prophylactic immunization. Nevertheless, more precise delineation of lymphocyte subset involvement can be obtained by cell replacement studies in some of these models or by exclusion of antibody. The outcomes of these approaches have been (or are) predictable in most cases. More fascinating, however, are the various instances which will be stressed where totally unpredicted and contrary observations have been made which led (or may lead) to fresh insight into the disease. These serendipitous findings illustrate at the same time the value of applying the manoeuvres, even though they imply that the logical immunologist cannot yet always outsmart the parasite by design.


2019 ◽  
Vol 102 (2) ◽  
pp. 511-520
Author(s):  
Yanrong Kuai ◽  
Xiaobo Gao ◽  
Huixia Yang ◽  
Haiyan Luo ◽  
Yang Xu ◽  
...  

Abstract Pentachloronitrobenzene (PCNB) is an organochlorine fungicide widely used for crop production and has become an environmental concern. Little is known about the effect of PCNB on ovarian steroidogenesis and follicular development. We found that PCNB stimulated Star expression and progesterone production in cultured rat granulosa cells in a dose-dependent manner. PCNB activated mitogen-activated protein kinase (MAPK3/1) extracellulat regulated kinase (ERK1/2), thus inhibition of either protein kinase A (PKA) or MAPK3/1 signaling pathway significantly attenuated progesterone biosynthesis caused by PCNB, suggesting that PCNB induced progesterone production by activating the cyclic adenosine monophosphate (cAMP/PKA) and MAPK3/1 signaling pathways. Further investigation demonstrated that PCNB induced Star expression and altered MAPK3/1 signaling in ovary tissues of immature SD rats treated with PCNB at the dose of 100, 200, or 300 mg/kg by daily gavage for 7 days, while serum progesterone level was dose-dependently decreased. We demonstrated that PCNB exposure accelerated the recruitment of primordial follicles into the growing follicle pool in ovary tissues, accompanied by increased levels of anti-Mullerian hormone (AMH) in both ovary tissues and serum. Taken together, our data demonstrate for the first time that PCNB stimulated Star expression, altered MAPK3/1 signaling and progesterone production in vivo and in vitro, and accelerated follicular development with a concomitant increase in AMH in ovary tissues and serum. Our findings provide novel insight into the toxicity of PCNB to animal ovary function.


2009 ◽  
Vol 21 (9) ◽  
pp. 108
Author(s):  
R. A. Keightley ◽  
B. Nixon ◽  
S. D. Roman ◽  
D. L. Russell ◽  
R. L. Robker ◽  
...  

Follicular development requires the recruitment of primordial follicles into the growing follicle pool following initiation of multiple cytokine signalling pathways. Suppression of follicular development is thought to be key to maintaining the population of primordial follicles and allowing for controlled release of these follicles throughout the reproductive lifespan of the female. However, little is known of the processes and signalling molecules that suppress primordial follicle activation and early follicle growth. Our group has identified significant upregulation of the Janus Kinase 2 (JAK2)/ Signal Transducer and Activator of Transcription 3 (STAT3) signalling pathway inhibitor the Suppressor of Cytokine Signalling 4 (SOCS4) that coincides with the initial wave of follicular activation in theneonatal mouse ovary. Further studies by our group have localised the SOCS4 protein to the granulosa cells of activating and growing follicles, suggesting SOCS4 expression may be linked to follicular activation. We have focused on examining protein localisation and gene expression patterns of the eight SOCS family members CIS and SOCS1-7. We have recently demonstrated that co-culture of neonatal ovaries with Kit Ligand (KL) for 2 days increases the mRNA levels of all SOCS genes. We also demonstrated the co-localisation of SOCS2 proteins with the KL receptor c-kit in the mural granulosa cells of antral, and large pre-antral follicles suggesting a significant role for SOCS2 in the later stages of follicular development. We have also shown that culturing ovaries with the potent JAK2 inhibitor AG490 substantially reduces mRNA levels of all SOCS and STAT genes that we have so far measured. We hypothesise a significant role for JAK2/STAT3 signalling in promoting the activation and early growth of ovarian follicles. Our investigations have identified significant roles for JAK2/STAT3 and the SOCS family in the regulation of ovarian follicle development.


Reproduction ◽  
2016 ◽  
Vol 151 (2) ◽  
pp. 105-115 ◽  
Author(s):  
Zhen Teng ◽  
Chao Wang ◽  
Yijing Wang ◽  
Kun Huang ◽  
Xi Xiang ◽  
...  

The reserve of primordial follicles determines the reproductive ability of the female mammal over its reproductive life. The primordial follicle is composed of two types of cells: oocytes and surrounding pre-granulosa cells. However, the underlying mechanism regulating primordial follicle assembly is largely undefined. In this study, we found that gap junction communication (GJC) established between the ovarian cells in the perinatal mouse ovary may be involved in the process. First, gap junction structures between the oocyte and surrounding pre-granulosa cells appear at about 19.0 dpc (days post coitum). As many as 12 gap junction-related genes are upregulated at birth, implying that a complex communication may exist between ovarian cells, because specifically silencing the genes of individual gap junction proteins, such as Gja1, Gja4 or both, has no influence on primordial follicle assembly. On the other hand, non-specific blockers of GJC, such as carbenoxolone (CBX) and 18α-glycyrrhetinic acid (AGA), significantly inhibit mouse primordial follicle assembly. We proved that the temporal window for establishment of GJC in the fetal ovary is from 19.5 dpc to 1 dpp (days postpartum). In addition, the expression of ovarian somatic cell (OSC)-specific genes, such as Notch2, Foxl2 and Irx3, was negatively affected by GJC blockers, whereas oocyte-related genes, such as Ybx2, Nobox and Sohlh1, were hardly affected, implying that the establishment of GJC during this period may be more important to OSCs than to oocytes. In summary, our results indicated that GJC involves in the mouse primordial follicle assembly process at a specific temporal window that needs Notch signaling cross-talking.


1994 ◽  
Vol 13 (1) ◽  
pp. 1-9 ◽  
Author(s):  
R Braw-Tal ◽  
D J Tisdall ◽  
N L Hudson ◽  
P Smith ◽  
K P McNatty

ABSTRACT The aim of this study was to investigate the sites of follistatin and α and βA inhibin mRNA expression in the ovaries of female sheep fetuses at 90, 100, 120 and 135 days of gestation (term=day 147). At 90 and 100 days primordial follicles were formed, followed by the appearance of primary follicles at 100 days of gestation. At days 120 and 135, primordial, primary and preantral (i.e. secondary) follicles were present in the ovaries, but antral (i.e. tertiary) follicles were not observed at any of these gestational ages. Two Booroola genotypes were studied: homozygous carriers (BB) and non-carriers (++) of the fecundity gene (FecB). Irrespective of genotype no specific hybridization of the α and βA inhibin riboprobes was detected in any ovarian cells at days 90, 100, 120 or 135 of gestation. In control mature ovaries, on the other hand, strong hybridization in the granulosa cells of antral follicles was observed. In contrast to α and βA inhibin, follistatin antisense (but not sense) riboprobes hybridized specifically to the granulosa cells of preantral follicles with two or more layers of cells at days 120 and 135 of gestation. Moreover, hybridization was also evident in the cells of the ovarian rete at days 120 and 135, but not at 90 or 100 days. No follistatin mRNA expression was observed in the granulosa cells of primordial or primary follicles or in any other ovarian cell type at any of the gestational ages examined. No FecB-specific differences in follistatin expression were noted with respect to stage of preantral follicular development and there were no obvious differences in the intensity of expression. These results show that follistatin mRNA is expressed specifically in the granulosa cells and intraovarian rete. Expression of follistatin in rete cells was coincident with the increasing numbers of growing follicles within the fetal ovary, indicating that rete cell function may have a role in the ontogeny of early follicular growth. Our results suggest that follistatin and α and βA inhibin may not be important for the initiation of follicle growth in the sheep ovary, since these genes are not expressed during the transformation of a primordial follicle to a primary structure. However, the evidence for follistatin mRNA expression in the ovine fetal ovary implies that this hormone is likely to play a role during the early stages of follicle growth.


Reproduction ◽  
2010 ◽  
Vol 139 (2) ◽  
pp. 309-318 ◽  
Author(s):  
R J Rodgers ◽  
H F Irving-Rodgers

Follicle classification is an important aid to the understanding of follicular development and atresia. Some bovine primordial follicles have the classical primordial shape, but ellipsoidal shaped follicles with some cuboidal granulosa cells at the poles are far more common. Preantral follicles have one of two basal lamina phenotypes, either a single aligned layer or one with additional layers. In antral follicles <5 mm diameter, half of the healthy follicles have columnar shaped basal granulosa cells and additional layers of basal lamina, which appear as loops in cross section (‘loopy’). The remainder have aligned single-layered follicular basal laminas with rounded basal cells, and contain better quality oocytes than the loopy/columnar follicles. In sizes >5 mm, only aligned/rounded phenotypes are present. Dominant and subordinate follicles can be identified by ultrasound and/or histological examination of pairs of ovaries. Atretic follicles <5 mm are either basal atretic or antral atretic, named on the basis of the location in the membrana granulosa where cells die first. Basal atretic follicles have considerable biological differences to antral atretic follicles. In follicles >5 mm, only antral atresia is observed. The concentrations of follicular fluid steroid hormones can be used to classify atresia and distinguish some of the different types of atresia; however, this method is unlikely to identify follicles early in atresia, and hence misclassify them as healthy. Other biochemical and histological methods can be used, but since cell death is a part of normal homoeostatis, deciding when a follicle has entered atresia remains somewhat subjective.


Reproduction ◽  
2006 ◽  
Vol 131 (3) ◽  
pp. 525-532 ◽  
Author(s):  
Karin A Slot ◽  
Jan Kastelijn ◽  
Anne Bachelot ◽  
Paul A Kelly ◽  
Nadine Binart ◽  
...  

GH influences female fertility. The goal of the present study was to obtain more insight into the effect of loss of GH signalling, as observed in humans suffering from Laron syndrome, on ovarian function. Therefore, serial paraffin sections of ovaries of untreated and IGF-I-treated female GH receptor knock-out (GHR/GHBP-KO) mice were examined to determine the follicular reserve and the percentage of follicular atresia in each ovary. Our observations demonstrate that the amount of primordial follicles was significantly elevated in GHR/GHBP-KO mice, while the numbers of primary, preantral and antral follicles were lower compared with wild-type values. The reduced number of healthy growing follicles in GHR/GHBP-KO mice was accompanied by a significant increase in the percentage of atretic follicles. IGF-I treatment of GHR/GHBP-KO mice for 14 days resulted in a reduced number of primordial follicles, an increased number of healthy antral follicles, and a decreased percentage of atretic follicles. The results of the present study suggest that GH may play a role, either directly or indirectly, via for instance IGF-I, in the recruitment of primordial follicles into the growing pool. Furthermore, GH seems to protect antral follicles, directly or indirectly from undergoing atresia.


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