scholarly journals Inhibition of matrix metalloproteinases in Siberian hamsters impedes photostimulated recrudescence of ovaries

Reproduction ◽  
2010 ◽  
Vol 140 (6) ◽  
pp. 875-883 ◽  
Author(s):  
Julie Whited ◽  
Asha Shahed ◽  
Carling F McMichael ◽  
Kelly A Young
Keyword(s):  
Matrix Metalloproteinases ◽  
Ovarian Function ◽  
Corpora Lutea ◽  
Gelatinase Activity ◽  
Antral Follicles ◽  
Mmp Inhibitor ◽  
Siberian Hamsters ◽  
First Time ◽  
Long Photoperiod

Exposure of Siberian hamsters to short photoperiod for 14 weeks induces ovarian regression. Subsequent transfer to long photoperiod restores ovarian function, and 2 weeks of photostimulation increases plasma estradiol (E2), antral follicles, and corpora lutea (CL). Because tissue remodeling involved with photostimulated ovarian recrudescence is associated with differential expression of matrix metalloproteinases (MMPs), we hypothesized that inhibiting MMP activity using a broad-spectrumin vivoMMP inhibitor, GM6001, would curtail recrudescence. One group of hamsters was placed in long days (LD; 16 h light:8 h darkness) for 16 weeks. Another group was placed in inhibitory short days (SD; 8 h light:16 h darkness) for 14 weeks. A third group was placed in SD for 14 weeks and transferred to LD for 2 weeks to stimulate recrudescence. During weeks 14–16, animals were either not treated or treated daily with i.p. injections of GM6001 (20 mg/kg) or vehicle (DMSO). GM6001 reduced gelatinase activity and decreased immunohistochemical staining for MMP1, MMP2, and MMP3 compared with vehicle. No differences between controls, vehicle, or GM6001 treatment were observed among LD animals, despite a trend toward reduction in CL and E2with GM6001. Although SD reduced ovarian function, photostimulation of transferred controls increased uterine mass, plasma E2, appearance of antral follicles, and CL. With GM6001 treatment, photostimulation failed to increase uterine mass, plasma E2, antral follicles, or CL. These data show, for the first time, thatin vivoGM6001 administration inhibits MMP activity in hamster ovaries during photostimulation, and indicate that this inhibition may impede photostimulated recrudescence of ovaries. This study suggests an intriguing link between MMP activity and return to ovarian function during photostimulated recrudescence.

scholarly journals Short photoperiod-induced ovarian regression is mediated by apoptosis in Siberian hamsters (Phodopus sungorus)

Reproduction ◽  
2006 ◽  
Vol 131 (4) ◽  
pp. 771-782 ◽  
Author(s):  
C S Moffatt-Blue ◽  
J J Sury ◽  
Kelly A Young
Keyword(s):  
Caspase 3 ◽  
Ovarian Function ◽  
Corpora Lutea ◽  
Control Data ◽  
Antral Follicles ◽  
Siberian Hamsters ◽  
Estradiol Secretion ◽  
Induced Changes ◽  
Active Caspase

Siberian hamster reproduction is mediated by photoperiod-induced changes in gonadal activity. However, little is known about how photoperiod induces cellular changes in ovarian function. We hypothesized that exposing female hamsters to short (inhibitory) as opposed to long (control) photoperiods would induce an apoptosis-mediated disruption of ovarian function. Ovaries and plasma from hamsters exposed to either long (LD, 16 h light:8 h darkness) or short (SD, 8 h light:16 h darkness) days were collected during diestrus II after 3, 6, 9 and 12 weeks and processed for histology or RIA respectively. Apoptosis was assessed byin situTUNEL and active caspase-3 protein immunolabeling. No significant differences were observed among LD hamsters for any parameter; therefore, these control data were pooled. SD exposure induced a decline in preantral follicles (P< 0.05), early antral/antral follicles (P< 0.01) and corpora lutea (P< 0.01) by week 12 as compared with LD. Terminal atretic follicles appeared by SD week 9; by week 12, these had become the predominant ovarian structures. Estradiol concentrations decreased by weeks 9 and 12 SD when compared with both LD and week-3 SD hamsters (P< 0.05); however, no changes were observed for progesterone. TUNEL-positive follicles in SD ovaries increased at week 3 and subsequently declined by week 12 as compared with LD ovaries (P< 0.01). Active capsase-3 protein immunostaining peaked at SD week 3 as compared with all other groups (P< 0.01). TUNEL and capsase-3 immunolabeling were localized to granulosa cells of late-preantral and early-antral/antral follicles. These data indicate that SD exposure rapidly induces follicular apoptosis in Siberian hamsters, which ultimately disrupts both estradiol secretion and folliculogenesis, resulting in the seasonal loss of ovarian function.

435. Follicle differentiation and luteinisation in the mouse is associated with hypoxia inducible factor activity

2008 ◽  
Vol 20 (9) ◽  
pp. 115
Author(s):  
K. Tam ◽  
D. Russell ◽  
K. Kind ◽  
J. Thompson
Keyword(s):  
Granulosa Cells ◽  
Target Genes ◽  
Ovarian Function ◽  
Egfp Expression ◽  
Corpora Lutea ◽  
Limited Information ◽  
Antral Follicles ◽  
Follicle Differentiation

Hypoxia inducible factors (HIF) are transcription factors that mediate the response to hypoxic stress. Under hypoxic conditions, HIF is stabilised, translocates to the nucleus, and binds to the Hypoxia Response Elements (HRE) upstream of numerous target genes involved in angiogenesis and glycolysis, including Vegf, Glut-1 and Ldha. Little is known about the role of HIFs in regulating ovarian function. In rat granulosa cells, FSH stimulates HIF 1α via the PI3K/Akt pathway, demonstrating a role for HIFs during follicular development. In contrast, there is limited information regarding the role of HIFs during corpus luteum formation. In this study we investigated whether HIFs play a role in follicle differentiation and luteinisation. Prepubertal C57Bl6 females were stimulated with eCG (5 IU) followed 46 h later by hCG (5 IU). Mice were sacrificed at 0, 4, 8, 12, 16 and 24 h post hCG and granulosa cells were collected for Western analysis of HIF-1a protein. To investigate HIF activation in the ovary, a transgenic reporter mouse line was developed by lenti-viral incorporation of an HRE (4)-SV40-eGFP construct. Ovaries were collected from mice plugged day 1, 4 and 8 for CL analysis in vivo.A time- dependent increase of HIF 1α protein levels in granulosa cells, maximal around time of ovulation, was observed. Ovaries from cycling HRE-eGFP transgenic mice exhibited no eGFP in primordial, primary or preantral follicles. Upon antrum formation, eGFP was evident in occasional sections in antral follicles but HIF signalling was restricted within the theca. In contrast, corpora lutea on pregnancy day 1, 4 and 8 readily expressed eGFP and eGFP expression increases as luteinisation progresses.These results demonstrate that in vivo HIFs may play a role in folliculogenesis, but this is restricted to theca cells of antral follicles before hCG stimulation. Following hCG, maximal HIF activity is associated with the time of ovulation. In addition, HIF activity is maintained during luteinisation.

IN-VITRO STEROIDOGENESIS OF NEWLY FORMED CORPORA LUTEA AND THE NON-LUTEAL OVARY IN THE RAT, RABBIT, HAMSTER AND GUINEA-PIG

1980 ◽  
Vol 84 (1) ◽  
pp. 101-108 ◽  
Author(s):  
P. F. TERRANOVA ◽  
S. K. SAIDAPUR ◽  
G. S. GREENWALD
Keyword(s):  
Guinea Pig ◽  
Corpus Luteum ◽  
Ovarian Function ◽  
Serum Testosterone ◽  
The Other ◽  
Corpora Lutea ◽  
Serum Progesterone ◽  
Antral Follicles ◽  
Baseline Levels

The steroidogenic abilities of the newly formed corpus luteum (8–10 h after ovulation) and the non-luteal ovary were compared in the guinea-pig, hamster, rabbit and rat using an invitro incubation technique. Histologically, newly formed rat corpora lutea (CL) were highly luteinized whereas the CL of the rabbit and guinea-pig were only partially luteinized. The CL of the hamster showed the least amount of luteinization. Serum progesterone was highest in the rat (18 ± 3 (s.e.m.) ng/ml). In the hamster, it was about 8 ng/ml, whereas in the rabbit and guinea-pig it was about 1 ng/ml. Serum androstenedione ranged between 0·5 and 1 ng/ml. Serum testosterone was lowest in the hamster (60 pg/ml) and highest in the rabbit (470 pg/ml), whereas in the rat and guinea-pig, testosterone levels were similar (about 240 pg/ml). Serum oestrogens were at baseline levels in all species. The CL of the rat exhibited considerably greater steroidogenic ability than the CL of the other species, producing 70 ± 6 ng progesterone/mg per h, 215 ± 14 pg androstenedione/mg per h, 49 ± 3 pg testosterone/mg per h, 3 pg oestrone/mg per h and 1 pg oestradiol/mg per h. Rabbit CL produced only progesterone (7 ± 2 ng/mg per h). Newly formed hamster CL produced none of the above steroids. In general, the ability of the CL to produce progesterone in vitro correlated with the degree of luteinization found by histological observation. Guinea-pig CL were embedded deeply in the ovary and could not be obtained without damage. Consequently, a portion of the ovary containing a corpus luteum was incubated. There was no difference in the steroid production by this portion of the ovary compared with the non-luteal ovary. The non-luteal ovary of the rat produced the highest amount of progesterone (10 ± 2 ng/mg per h). The guinea-pig non-luteal ovary produced about 5 ± 2 ng progesterone/mg per h, whereas the non-luteal ovary of the rabbit did not produce any. On the other hand, the hamster non-luteal ovary lost progesterone. Non-luteal ovaries from all species produced androgens. The non-luteal ovary of the guinea-pig contained especially large numbers of atretic antral follicles. The guinea-pig non-luteal ovary produced extremely large amounts of androstenedione (1110 ± 210 pg/mg per h) and testosterone (606 ± 154 pg/mg per h) compared with the amounts produced by the non-luteal ovary of the rat, hamster and rabbit. In the non-luteal ovary, interstitium and atretic antral follicles are the probable source of androgens. Oestrogen production by the non-luteal ovary was at baseline levels in the four species studied correlating with the absence of healthy antral follicles. The results indicate the extreme species differences that exist in ovarian function in the early postovulatory period.

58 OVARIAN DOWN-REGULATION WITH ORAL PROGESTIN FOR FIXED-TIME LAPAROSCOPIC OVIDUCTAL ARTIFICIAL INSEMINATION WITH FRESHLY COLLECTED AND FROZEN–THAWED SPERMATOZOA IN DOMESTIC CATS

2014 ◽  
Vol 26 (1) ◽  
pp. 143 ◽  
Author(s):  
W. F. Swanson ◽  
J. Newsom ◽  
L. A. Lyons ◽  
R. A. Grahn ◽  
H. L. Bateman
Keyword(s):  
Ovarian Function ◽  
Fixed Time ◽  
Ovarian Activity ◽  
Corpora Lutea ◽  
Domestic Cats ◽  
Soy Lecithin ◽  
Frozen Semen ◽  
Progestin Treatment ◽  
Relative Fertility

Laparoscopic oviductal AI (LO-AI) with low numbers of freshly collected or frozen-thawed spermatozoa has resulted in high pregnancy success (50–70%) in domestic cats. However, proper timing of AI depends on identifying anestrual, non-luteal queens before exogenous gonadotropin injection, confounding AI scheduling and limiting applicability with felids housed at distant institutions. Recent research (Stewart et al. 2012 Biol. Reprod. 87, 1–11) has shown that daily oral progestin treatment is effective for down-regulating ovarian activity in cats and allowing synchronized stimulation with exogenous gonadotropins. Our study objectives were to (1) assess the effect of oral progestin treatment on pregnancy success following LO-AI in domestic cats and (2) compare relative fertility following LO-AI of each female with low numbers of freshly collected versus frozen-thawed spermatozoa. Young (<2 years old), nulliparous domestic cats were assigned to either control (Con; n = 8) or oral progestin (OP; n = 7) treatment groups. Con females were monitored daily for behavioural oestrus and blood samples from anestrual females assessed for progesterone concentration to confirm non-luteal status before exogenous gonadotropin treatment [100 IU of eCG followed 85 h later with 1000 IU of porcine LH (pLH)]. Oral progestin females were fed altrenogest (Regu-Mate; 0.088 mg kg–1 of body weight) mixed in moist cat food for 38 consecutive days and then treated with exogenous gonadotropins 6 days after altrenogest cessation. At 31 to 33 h post-pLH treatment, each female was inseminated via laparoscopy in 1 oviduct with freshly collected sperm (motile) from 1 male and frozen-thawed sperm (motile; frozen in a soy lecithin-based cryomedium) from a second male. Ultrasonography was conducted approximately Day 21 post-AI for pregnancy diagnosis. Pregnant females were spayed immediately and recovered fetuses assessed for paternity using short tandem repeat molecular marker analysis to determine relative fertility of fresh versus frozen semen. All females ovulated following gonadotropin treatment, averaging ( ± standard error of the mean) 20.6 ± 1.7 corpora lutea per queen. Most [12/15 (80%)] females conceived following LO-AI, producing an average of 8.1 ± 1.4 implantations and 5.9 ± 1.2 fetuses per pregnancy. There was no difference (P > 0.05) between Con and OP cats in pregnancy success [Con: 6/8 (75%); OP: 6/7 (86%)] or in mean implantation number (Con: 6.0 ± 1.8; OP: 10.2 ± 2.0) or fetal number (Con: 4.3 ± 1.6; OP: 7.5 ± 1.6) in pregnant cats. Paternity assessment revealed that freshly collected and frozen-thawed spermatozoa were equally effective (P > 0.05) in producing pregnancies (fresh: 11/15 (73%); frozen: 10/15 (67%)], with no difference (P > 0.05) in total fetal numbers [fresh: 37/69 (54%); frozen: 32/69 (46%)]. These results indicate that oral progestin treatment may be used to down-regulate ovarian function in felids for fixed-time AI without compromising fertility in vivo, and that LO-AI with low numbers of cat sperm frozen in a soy lecithin medium may produce high pregnancy percentages and normal litter sizes.

scholarly journals Ovarian Expression of Insulin-Like Peptide 3 (INSL3) and Its Receptor (RXFP2) During Development of Bovine Antral Follicles and Corpora Lutea and Measurement of Circulating INSL3 Levels During Synchronized Estrous Cycles

Endocrinology ◽  
2013 ◽  
Vol 154 (5) ◽  
pp. 1897-1906 ◽  
Author(s):  
Leanne Satchell ◽  
Claire Glister ◽  
Emma C. Bleach ◽  
Richard G. Glencross ◽  
Andrew B. Bicknell ◽  
...  
Keyword(s):  
Granulosa Cell ◽  
Major Product ◽  
Corpora Lutea ◽  
Potential Contribution ◽  
Mrna Levels ◽  
Estrous Cycles ◽  
Lh Surge ◽  
Antral Follicles

Abstract Insulin-like peptide 3 (INSL3), a major product of testicular Leydig cells, is also expressed by the ovary, but its functional role remains poorly understood. Here, we quantified expression of INSL3 and its receptor RXFP2 in theca interna cell (TIC) and granulosa cell compartments of developing bovine antral follicles and in corpora lutea (CL). INSL3 and RXFP2 mRNA levels were much higher in TIC than granulosa cell and increased progressively during follicle maturation with INSL3 peaking in large (11-18 mm) estrogen-active follicles and RXFP2 peaking in 9- to 10-mm follicles before declining in larger (11-18 mm) follicles. Expression of both INSL3 and RXFP2 in CL was much lower than in TIC. In situ hybridization and immunohistochemistry confirmed abundant expression of INSL3 mRNA and protein in TIC. These observations indicate follicular TIC rather than CL as the primary site of both INSL3 production and action, implying a predominantly autocrine/paracrine role in TIC. To corroborate the above findings, we showed that in vitro exposure of TIC to a luteinizing concentration of LH greatly attenuated expression of both INSL3 and its receptor while increasing progesterone secretion and expression of STAR and CYP11A1. Moreover, in vivo, a significant cyclic variation in plasma INSL3 was observed during synchronized estrous cycles. INSL3 and estradiol-17β followed a similar pattern, both increasing after luteolysis, before falling sharply after the LH surge. Thus, theca-derived INSL3, likely from the dominant preovulatory follicle, is detectable in peripheral blood of cattle, and expression is down-regulated during luteinization induced by the preovulatory LH surge. Collectively, these findings underscore the likely role of INSL3 as an important intrafollicular modulator of TIC function/steroidogenesis, while raising doubts about its potential contribution to CL function.

scholarly journals 265.Matrix metalloproteinases in the mouse model of menstruation: effect of doxycycline inhibition

2004 ◽  
Vol 16 (9) ◽  
pp. 265
Author(s):  
J. Shen ◽  
J. Zhang ◽  
T. J. Kaitu'u ◽  
M. Brasted ◽  
L. A. Salamonsen
Keyword(s):  
Matrix Metalloproteinases ◽  
Mouse Model ◽  
Functional Significance ◽  
Human Endometrium ◽  
Tissue Destruction ◽  
Apparent Effect ◽  
Gelatinase Activity ◽  
Old World ◽  
Uterine Lumen ◽  
Mmp Inhibitor

Strong correlative evidence supports a role for matrix metalloproteinases (MMP) in the tissue breakdown at menstruation. Because menstruation occurs only in women and a few old-world primates, it has not been possible to examine the functional significance of potentially key mediators of this process. To this end, we developed a mouse model for menstruation (1), in which ovariectomised mice are subjected to a decidualising stimulus: injection of oil into the uterine lumen following appropriate hormone-priming. During the 24 h following withdrawal of progesterone (P), the decidualised tissue progressively breaks down, in a manner that morphologically resembles that of human endometrium at menstruation. The aims of the present study were to examine the pattern of MMP expression during the time from progesterone withdrawal until complete tissue breakdown, and to determine whether administration of doxycycline, (a known MMP modulator), 3 h prior to P withdrawal, affected the expression or activity of the MMPs or restrained the tissue destruction. MMP-3 was present at foci in the decidual zone: these were initially associated with the restructuring at decidualisation and subsequently with the tissue destruction. MMP-7 was detected both in epithelium and in leukocytes, predominantly neutrophils. These were first apparent in the basal zone during the earliest stages of tissue instability, and dramatically increased in numbers as breakdown progressed. MMP-9 was found only in leukocytes, predominantly neutrophils and some macrophages, with greatly increased numbers with time. Zymography revealed a dramatic increase in both latent and active MMP-9 as tissue breakdown proceeded. Doxycycline reduced immunoreactive MMP-3 but not MMP-7 or MMP-9 in the tissue, and also decreased gelatinase activity. However, no apparent effect on tissue breakdown was observed. Further studies with a more potent MMP inhibitor are required to fully establish the importance of MMPs in these processes. (1) Brasted et al. (2003) Biol. Reprod. 69, 1273.

Ultrasound biomicroscopy: a non-invasive approach for in vivo evaluation of oocytes and small antral follicles in mammals

2014 ◽  
Vol 26 (1) ◽  
pp. 48 ◽  
Author(s):  
L. F. M. Pfeifer ◽  
G. P. Adams ◽  
R. A. Pierson ◽  
J. Singh
Keyword(s):  
Ovarian Function ◽  
Ultrasound Biomicroscopy ◽  
Biomedical Sciences ◽  
Depth Of Penetration ◽  
In Vivo Evaluation ◽  
Invasive Approach ◽  
Antral Follicles ◽  
Advantages And Disadvantages ◽  
And Control

The use of ultrasonography has changed our understanding of the ovarian function in live animals. However, most of the studies that have used ultrasonography to image the ovary have provided data only of structures >1 mm in diameter. The recent availability of high-resolution ultrasound technology with high-frequency transducers (25–70 MHz), offers the potential to examine the developmental dynamics of small antral follicles and the cumulus–oocyte complex (COC) in vivo. In this review we provide data from a series of studies performed by Veterinary Biomedical Sciences Laboratory describing the advantages and disadvantages, as well as image characteristics, of ultrasound biomicroscopy (UBM) to study ovarian biology in mammals. Data and images of small ovarian structures in rabbits, cattle, mice and humans are shown. The UBM technique allowed visualisation of small antral follicles ranging in size from 300 to 700 μm in all species examined, as well as COC within follicles in rabbits, cattle and humans. Furthermore, UBM permitted clear distinction of the follicular wall from the surrounding ovarian stroma in cattle and humans. At present, the limited depth of penetration of UBM restricts the use of this technique to an experimental setting. In that regard, further studies using UBM will probably result in a greater understanding of the pattern and control of early antral folliculogenesis and oogenesis.

scholarly journals Transcriptome analysis during photostimulated recrudescence reveals distinct patterns of gene regulation in Siberian hamster ovaries†

2019 ◽  
Vol 102 (3) ◽  
pp. 539-559
Author(s):  
Kathleen Leon ◽  
Jon D Hennebold ◽  
Suzanne S Fei ◽  
Kelly A Young
Keyword(s):  
Ovarian Function ◽  
Expression Patterns ◽  
Reproductive Function ◽  
Systematic Investigation ◽  
Ovarian Activity ◽  
Corpora Lutea ◽  
Gonadotropin Secretion ◽  
Siberian Hamsters ◽  
Ovary Function ◽  
Ovarian Cyclicity

Abstract In Siberian hamsters, exposure to short days (SDs, 8 h light:16 h dark) reduces reproductive function centrally by decreasing gonadotropin secretion, whereas subsequent transfer of photoinhibited hamsters to stimulatory long days (LDs, 16 L:8 D) promotes follicle stimulating hormone (FSH) release inducing ovarian recrudescence. Although differences between SD and LD ovaries have been investigated, a systematic investigation of the ovarian transcriptome across photoperiod groups to identify potentially novel factors that contribute to photostimulated restoration of ovarian function had not been conducted. Hamsters were assigned to one of four photoperiod groups: LD to maintain ovarian cyclicity, SD to induce ovarian regression, or post transfer (PT), where females housed in SD for 14-weeks were transferred to LD for 2-days or 1-week to reflect photostimulated ovaries prior to (PTd2) and following (PTw1) the return of systemic FSH. Ovarian RNA was extracted to create RNA-sequencing libraries and short-read sequencing Illumina assays that mapped and quantified the ovarian transcriptomes (n = 4/group). Ovarian and uterine masses, plasma FSH, and numbers of antral follicles and corpora lutea decreased in SD as compared to LD ovaries (P &lt; 0.05). When reads were aligned to the mouse genome, 18 548 genes were sufficiently quantified. Most of the differentially expressed genes noted between functional LD ovaries and regressed SD ovaries; however, five main expression patterns were identified across photoperiod groups. These results, generally corroborated by select protein immunostaining, provide a map of photoregulated ovary function and identify novel genes that may contribute to the photostimulated resumption of ovarian activity.

scholarly journals 220.TGFβ1 deficient mice exhibit impaired follicle growth and luteal maintenance

2004 ◽  
Vol 16 (9) ◽  
pp. 220
Author(s):  
R. L. Robker ◽  
W. V. Ingman ◽  
S. A. Robertson
Keyword(s):  
Cell Proliferation ◽  
Granulosa Cell ◽  
Transforming Growth Factor ◽  
Ovarian Function ◽  
Follicular Development ◽  
Luteal Cell ◽  
Corpora Lutea ◽  
Normal Female ◽  
Female Reproduction ◽  
Antral Follicles

Transforming Growth Factor β1 (TGFβ1) is essential for normal female reproduction. Mice with a targeted deletion in the TGFβ1 gene (TGFβ1–/–) have severely impaired fertility with pregnancy occurring in <25% of mated females. TGFβ1 is implicated in several aspects of ovarian function, including potentiation of granulosa cell proliferation and suppression of luteal cell apoptosis. Our initial observations indicate that estrous cycling is disrupted in TGFβ1–/– mice and that ovulation rate is reduced. To further investigate how impaired ovarian function contributes to the infertility of TGFβ1–/– mice, ovaries were isolated from TGFβ1+/+ and TGFβ1–/– littermates at proestrus and fixed and sectioned for examination of follicle morphology and growth. BrdU labelling was performed to detect granulosa cell proliferation and blood samples were obtained for analysis of gonadotrophins and ovarian steroid hormones. Histological examination showed that ovaries from TGFβ1–/– mice were smaller than those of TGF–1+/+ mice, however large antral follicles were observed, indicating that TGFβ1 is not essential for granulosa cell proliferation. Compared to TGFβ1+/+ ovaries however, there were fewer antral follicles and only rare corpora lutea. Interestingly, in some cases there were large numbers of macrophages surrounding small follicles suggesting increased follicular atresia and/or altered macrophage activity in the TGFβ1–/– ovaries. Ovaries and serum were also isolated from females at d4 post-coital for assessment of corpora lutea morphology. TGFβ1–/– ovaries weighed less and had fewer corpora lutea than TGFβ1+/+ ovaries. TGFβ1–/– corpora lutea also contained increased numbers of apoptotic cells and infiltrating macrophages indicative of premature luteal regression. Circulating progesterone levels were reduced in TGFβ1–/– females, as was progesterone production per corpus luteum further indicating a functional defect in luteal maintenance. Cumulatively these observations show that TGFβ1 has essential roles in regulation of ovarian macrophage populations, in normal follicular development and in the generation, maintenance and steroidogenic function of corpora lutea.

244. Effect of batimastat, a specific inhibitor of matrix metalloproteinases, on endometrial breakdown and repair in a mouse model

2005 ◽  
Vol 17 (9) ◽  
pp. 97
Author(s):  
T. J. Kaitu'u ◽  
N. B. Morison ◽  
L. A. Salamonsen
Keyword(s):  
Matrix Metalloproteinases ◽  
Mouse Model ◽  
Expression Patterns ◽  
Specific Inhibitor ◽  
Apparent Difference ◽  
Cross Sectional ◽  
Gelatinase Activity ◽  
Expected Time ◽  
Mmp Inhibitor

Strong correlative evidence supports a role for matrix metalloproteinases (MMPs) in the tissue breakdown at menstruation. As menstruation occurs in very few species besides women, there is a lack of suitable and easily accessible animal models available to examine the functional significance of potential key mediators of this process. A mouse model of endometrial breakdown and repair has been developed,1 which morphologically resembles that of human endometrium at menstruation. Previous studies in our laboratory showed that the expression patterns of various MMPs in the mouse model closely resembled those seen in the human.2 Administration of doxycycline, a broad spectrum MMP inhibitor, decreased gelatinase activity, but had no effect on tissue breakdown in this model. The aim of the present study was to further examine the importance of MMPs in endometrial breakdown and repair via administration of batimistat, a highly potent and specific MMP inhibitor. Batimistat was administered I.P to mice 24 h prior to the expected time of endometrial breakdown. The efficacy of batimistat within the uterus was proven using in situ zymography, which identifies MMP activity (rather than latent forms). This demonstrated that batimistat was reaching its target organ and effectively inhibiting MMP activities (both gelatinase and collagenase). Examination of gross uterine morphology revealed no apparent difference between groups, with batimistat treated uteri displaying a similar extent of tissue breakdown and repair to their control counterparts. Measurement of the breaking down area compared to total endometrial area revealed no difference between control and batimistat treatment, with the breaking down areas being 69 ±13% and 72 ± 9.8% of total endometrial cross-sectional area respectively. There was likewise no effect on endometrial repair. The results of this study together with our previous study using doxycycline, indicate that MMPs are not the key mediators of endometrial breakdown in this model. (1)Shen et al. (2004) Reprod. Fert. Dev. 16(Suppl), A265, p. 97.(2)Brasted et al. (2003) Biol. Reprod. 69, 1273.

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