| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
RESEARCH |
and ß, androgen receptor and progesterone receptor mRNA and protein localisation within the developing ovary and in small growing follicles of sheep
AgResearch, Wallaceville Animal Research Centre, Ward Street, PO Box 40063, Upper Hutt, New Zealand
Correspondence should be addressed to J Juengel; Email: jenny.juengel{at}agresearch.co.nz
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionAcknowledgementsReferences |
|---|
and ß form; ER and ERß respectively), androgen (AR) and progesterone (PR) were determined by in situ hybridisation and immunohistochemistry in ovine ovarian tissues collected during ovarian development and follicular formation (days 26–75 of fetal life) as well as during the early stages of follicular growth. Expression of ERß was observed early during ovarian development and continued to be expressed throughout follicular formation and also during the early stages of follicular growth. ERß was identified in germ cells as well as in the granulosa cells. At the large preantral stage of follicular growth, expression of ER was also consistently observed in granulosa cells. AR was first consistently observed at day 55 of fetal life in stroma cells throughout the ovary. Within the follicle, expression was observed in granulosa and thecal cells from the type-2 to -3 stage of follicular growth. PR mRNA did not appear to be expressed during ovarian development (days 26–75 of gestation). However, PR (mRNA and protein) was observed in the theca of type-3 (small preantral) and larger follicles, with mRNA – but not protein – observed in granulosa cells of some type-4 and 5 follicles. Expression of ERß, ER and AR, as well as PR, was also observed in the surface epithelium and ovarian stroma of the fetal, neonatal and adult ovary. Thus, in sheep, steroid hormones have the potential to regulate the function of a number of different ovarian cell types during development, follicular formation and early follicular growth. |
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionAcknowledgementsReferences |
|---|
A critical role for steroids in regulating follicular growth has also been shown with the development of abnormal ovarian phenotypes associated with reduced fertility in mice lacking steroid receptors (Lydon et al. 1996, Drummond et al. 2002, Yeh et al. 2002). Some of these effects are related to changes in other hormones regulated by steroids – such as gonadotrophins – or follicular processes occurring late during follicular development; however, there is also growing evidence supporting a direct intra-ovarian role for steroids, particularly oestrogens and androgens, in regulating early follicular growth (Koering et al. 1994, Drummond et al. 2002, Britt et al. 2004, Jonard & Dewailly 2004). A key aspect to gaining greater understanding of how steroid hormones may be influencing ovarian development is first to determine which ovarian cell types have receptors to steroids. Thus, the objectives of this experiment were to identify the cell types capable of responding to oestrogen, androgens and progestins during prenatal ovarian development and the early stages of follicular growth, which begins during fetal life and continues throughout the animal’s life; the experiments were carried out in a species known to synthesise steroids during ovarian development, namely sheep.
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionAcknowledgementsReferences |
|---|
In situ hybridisation
Except where indicated, laboratory chemicals were obtained from BDH Chemicals New Zealand Ltd (Palmerston North, New Zealand), Invitrogen or Roche. Complementary cDNAs encoding a portion of the ovine progesterone receptor (PR; bases 62–359 of U30300
[GenBank]
; Genbank accession number), oestrogen receptor (ER and ERß; bases 1088–1573 of Z49257
[GenBank]
and 1–416 of AF177936
[GenBank]
respectively) and androgen receptor (AR; bases 2356–2899 of M21748
[GenBank]
) were generated using standard RT-PCR techniques. Sequences of resulting plasmids were confirmed prior to use for in situ hybridisation. In situ hybridisation was performed as previously described (Tisdall et al. 1999) with minor modifications. The ovaries from at least four animals were examined for expression of each of the receptor genes at all ages during gonadal development (days 26–75). Follicles of each listed classification were observed in at least four animals (day 135 of fetal life to adult) for all receptor genes. Classification of follicles (types 1 to 5) was based on the system outlined previously (Lundy et al. 1999): type 1/1a consists of an oocyte surrounded by a single layer of flattened or mixed flattened and cuboidal cells; type 2 contain 1 to < 2 layers of cuboidal granulosa cells; type 3 contain 2 to < 4 layers of cuboidal granulosa cells; type 4 have > 4 layers of granulosa cells and a well-defined theca but have not yet formed an antrum; type 5 have multiple layers of granulosa cells, a well-defined theca and a defined antrum. All follicles with signs of degeneration (i.e. pyknotic granulosa cells, lack of a distinct basement membrane or degenerate oocytes) were excluded from the study. Non-specific hybridisation was monitored by hybridising the sense RNA for each receptor to tissue collected from at least one animal per age group. Hybridisation was considered specific when the intensity of silver grains, as measured by visual assessment, over a cellular type was greater than that observed in the area of the slide not containing tissue. For all genes, hybridisation of the sense RNA over the tissue section was similar or lower in intensity to that observed on the areas of the slide not containing tissue of both the sense and antisense hybridised slides; and thus was considered to be non-specific (data not shown).
Immunohistochemistry
Immunohistochemistry to localise the presence of steroid receptor was used to confirm the presence of receptor protein in cellular types containing the mRNA. At least three animals at days 28–30, 35–40 and 55–75 were examined for the presence of the oestrogen and androgen receptor proteins. In addition, the ovaries from at least three animals were studied to identify the presence or absence of oestrogen, androgen and progesterone receptor protein for each follicular type. Immunohistochemistry was performed as previously described using a pressure-cooker antigen-retrieval method with minor modifications (Tisdall et al. 1999, Quirke et al. 2001). Briefly, following horseradish-peroxidase labelling of the secondary antibody (diluted 1:500; DAKO (DAKO Corporation, Carpinteria, CA, USA) swine anti-rabbit or rabbit anti-mouse purified immunoglobulin G (IgG)) with a DAKO ABC kit, staining sensitivity was increased using NEN tyramide signal amplification kit (New England Nuclear; Perkin Elmer Life Sciences, Boston, MA, USA). The chromagen was 3,3'-diaminobenzidine tetrahydrochloride (DAB) with haematoxylin counterstaining. The primary antibodies utilised in this study were mouse anti-bovine oestrogen receptor (12.5 µg/ml; catalogue number 05–394, Upstate Biotechnology, Charlottesville, VA, USA), mouse anti-oestrogen receptor beta 1 (20 (postnatal) or 40 (fetal) µg/ml, clone PPG5/10; catalogue number MCA1974S, Serotec Ltd, Oxford, UK), rabbit anti-human androgen receptor (5 µg/ml; catalogue number sc-816, Santa Cruz Biotechnology, Inc., Santa Cruz, CA, USA) and mouse anti-progesterone receptor (20 µg/ml, clone aPR-6; catalogue number MA1-411, Affinity Bioreagents, Inc., Golden, CO, USA); this latter antibody detects only the B form of the PR and was only suitable for examination of lamb and adult ovaries as non-specific cytoplasmic staining was very high in fetal tissue. Antibody raised against a partially purified PR from nuclear extracts was trialled but was found to be unsuitable as it appeared to stain almost all cells in the ovary non-specifically. Modifications to the method included the use of a 1 mM EDTA buffer, pH 8.0, for antigen retrieval for the PR and the use of 0.1 M TRIS buffer for all steps except the primary antibody incubation (0.5 M TRIS buffer). Non-specific staining was determined by replacing the primary antibody with an equivalent amount of non-immune IgG and, when available, pre-adsorption of the primary antibody with the antigen used for immunisation.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionAcknowledgementsReferences |
|---|
ER
Specific expression of mRNA for ER was first observed on day 55 of fetal life (Fig. 1
and Table 1). A strong signal was observed in the surface epithelium and in cells entering the ovigerous cords. The hybridisation pattern observed on day 75 of fetal life was similar to that at day 55 with the strongest signal observed in the surface epithelium and pre-granulosa cells within the ovigerous cords closest to the ovarian surface, with a lower level of signal observed in connective tissue. Expression continued to be observed in the surface epithelium and ovarian stroma in both lamb and adult ewes. No signal above background was observed in type-1 to -3 follicles (Fig. 1 and Table 2). Specific hybridisation was observed in granulosa cells of type-4 and -5 follicles but not in oocytes or thecal cells (Fig. 1, Table 2). Expression was also observed in the corpus luteum when present.
|
|
|
protein localisation was similar to that observed for ER mRNA. Before day 55 of gestation, faint immunostaining for ER protein was occasionally observed in cells of the surface epithelium as well as in pre-granulosa and stroma cells. However, strong consistent staining was observed on days 55 and 75 (Fig. 2) of gestation. Staining intensity was strongest in the cells of the surface epithelium and pre-granulosa cells near the surface of the ovary with a weaker signal being observed in stromal cells. ER protein was observed in the surface epithelium of both lamb and adult ovaries (Fig. 2). Staining for ER protein was occasionally observed in granulosa cells of type-1 to -3 follicles with most granulosa cells staining in type-4 and -5 follicles (Fig. 2). Staining in thecal cells was inconsistent. Occasionally, oocytes appeared to stain lightly for ER but similar sporadic staining was also observed in the negative-control slides (see Fig. 4D for a non-immune mouse sera negative control). Strong staining for ER protein was also observed in stromal cells, especially those around small follicles in the cortex of the ovary (Fig. 2) and around blood vessels (data not shown). Expression in luteal tissue was associated with the large luteal cells (Fig. 2).
|
|
, Table 1
). Expression was also evident after ovigerous cord formation (i.e. days 55 and 75; Table 1) and was noted within the ovigerous cords, in germ cells and possibly also in the pre-granulosa cells. Outside the ovigerous cords, expression was observed in the mesonephric-derived cell streams. Newly formed follicles expressed ERß mRNA in both granulosa cells and oocytes (Fig. 3). For all stages of follicular growth that were examined (i.e. types 1/1a to 5) ERß mRNA was present in oocytes, granulosa cells and the theca – which was first clearly identified in some type-3 follicles (Fig. 3, Table 2). Expression was observed in ovarian rete (n = 3, Fig. 3) and occasionally in isolated stromal cells. Consistent expression of ERß mRNA was not observed in the surface epithelium, the vascular system or luteal tissue.
|
). The presence of the protein continued to be widespread in the developing ovary including cells of the surface epithelium (varied numbers, often limited), central blastema and stroma; as well as in germ cells (Fig. 4). Expression was also observed in pre-granulosa cells, particularly as the ovigerous cords developed. Expression of ERß protein was observed in both the granulosa cells and oocyte of the newly formed follicles (data not shown). A limited number of cells in the surface epithelium continued to express ERß protein in both lamb and adult ovaries. Expression of ERß protein was also observed in both granulosa cells and oocytes of all types of follicles examined (Fig. 4) with weak signal observed in the theca of type-3 and greater follicles. ERß protein was also observed in stromal cells, particularly in areas containing numerous small (types 1 to 3) follicles. Some cells of the corpus luteum stained positive for ERß protein (data not shown).
AR
Consistent expression of mRNA encoding AR was first observed on day 55 of gestation when a faint signal was observed in the connective tissue of the ovarian medulla of all animals. By day 75, expression levels had increased with signal in connective tissue throughout the ovary, including the mesonephric-derived cell streams (Fig. 5, Table 1). However, expression was not observed inside the ovigerous cords. Expression of AR mRNA was not observed in type-1 and -2 follicles (Fig. 5) but was observed in the granulosa cells of many type-3 follicles. Strong expression of AR was also observed in the stroma, particularly around small growing follicles and thus it was difficult to determine if theca cells of type-3 follicles expressed mRNA encoding AR or if the signal observed was associated with the surrounding stroma. Both thecal and granulosa cells expressed mRNA encoding AR in type-4 and -5 follicles. Expression was also observed in luteal tissue (n = 5) and in scattered cells of the surface epithelium, albeit weakly.
|
, Table 1). AR protein was also identified in many oocytes of follicles at all stages of development. However, staining was also observed in the oocytes of some follicles following incubation with non-immune sera. Thus, it was not possible to demonstrate unequivocally the presence of AR protein in oocytes. Granulosa cells of type-2 to -5 follicles and theca of type-3 to -5 follicles were positive for AR protein. AR protein was also localised in some cells of the surface epithelium, most stromal cells and also luteal cells.
|
). During follicular development, expression was observed in the theca of type-3 to -5 follicles. In addition, the granulosa cells of some type-4 and -5 follicles expressed PR mRNA faintly (Fig. 7, Table 2). Some cells of both the ovarian stroma and surface epithelium expressed PR mRNA and a weak signal was observed in luteal tissue (n = 3; data not shown).
|
). During follicular growth, PR protein was not consistently observed until the type-3 stage of development and was restricted to theca cells even though granulosa cells as well as thecal cells had been shown to express PR mRNA (Fig. 8, Table 2). In addition, no staining was observed in luteal tissue while faint signal for PR mRNA was observed in this tissue. It is important to note that the immunohistochemistry methodology for the detection of PR resulted in a high, non-specific staining in the cytoplasm of many cells of the ovary. This non-specific staining complicates detection of specific staining and could mask specific staining for the receptor in the nucleus of the cell. This may account for the discrepancy between the in situ hybridisation results and the immunohistochemistry results.
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionAcknowledgementsReferences |
|---|
and ERß in a similar pattern as observed in the current study (Pepe et al. 2002). Further studies to examine the potential role of oestrogens in ovarian development in baboons showed that inhibition of oestrogen synthesis during the second half of gestation, by administration of an aromatase inhibitor, resulted in a disruption of normal follicular formation (Zachos et al. 2002). Furthermore, 10-week-old mice lacking aromatase have recently been shown to have fewer primordial and primary follicles then wild-type controls (Britt et al. 2004). Collectively, these data support a critical role for oestrogens in follicular formation.
Cells of the surface epithelium of the developing gonad also expressed ERs. In sheep, cells of the surface epithelium are mitotically very active during much of fetal life and most granulosa cells originate from the surface epithelium (Sawyer et al. 2002). Thus, a role for oestrogen in regulating the proliferation of these cells could be postulated. However, the role of oestrogen in regulating surface epithelial cells from adult animals is equivocal, with both stimulation and inhibition of proliferation observed (Bai et al. 2000, Murdoch & Van Kirk 2002, Wright et al. 2002). It seems likely that before day 55 of gestation, oestrogen regulation would occur primarily through the ERß localised to a limited number of cells of the surface epithelium. Between days 40 and 55 of gestation there is a strong up-regulation of expression of ER. This corresponds to a time when cells from the surface epithelium contribute a large number of pre-granulosa cells to the ovigerous cords. However, once differentiation of the surface epithelium cell to a pre-granulosa cell (i.e. association with the germ cell) occurs, ER (unlike ERß) was down-regulated as expression of ER was not observed in either the forming or newly-formed follicles.
ERs were also observed in stromal cells as well as the mesonepheric-derived cell streams. Previous studies have described an association between the mesonephric-derived cell streams and the developing vasculature of the ovary (Juengel et al. 2002, Sawyer et al. 2002). In addition, abnormal ovarian morphology was observed in mice lacking the aromatase gene: these animals show a disorganisation of the stroma with an increase in collagen deposition in aging animals (Britt et al. 2000). Thus, it is possible that paracrine interaction occurs between oestradiol and ER and ERß to influence the stroma and vascular network in the developing ovary.
While there is evidence to support a role for oestrogens in influencing ovarian development from early fetal life, androgens – by contrast – are unlikely to influence intra-ovarian events until later in fetal life as AR was not consistently expressed until day 55. Moreover, testosterone was not detectable in the developing ovary between days 30 and 75 of fetal life, although significant amounts of androstenedione were present at day 75 (Quirke et al. 2001). It is possible that biologically significant amounts of androgens were made earlier during gonadal development but were not detectable with the RIA as most if not all was metabolised to oestradiol. The strongest expression of AR mRNA occurred in stromal cells and cells migrating into the ovary from the mesonephros. Thus, it seems most likely that the most profound effects of androgens are on the ovarian stroma and vasculature mainly after day 40 of fetal life.
After follicles had formed, ERß mRNA and protein continued to be present in both the granulosa cells and oocytes of type-1/1a and small growing follicles and was also detected in the theca, which was present from the type-3 stage of growth. This confirms and extends the previous findings of ERß protein in granulosa cells of ovine preantral and antral follicles (Cardenas et al. 2001) and ERß mRNA in ovine antral follicles during the follicular phase (Jansen et al. 2001). In addition, similar to previous reports (Tomanek et al. 1997), ER protein was detected in some type-1 to -3 follicles with consistent detection of both mRNA and protein observed in the granulosa cells of type-4 (late preantral) and antral follicles. The inability to detect ER mRNA prior to the type-4 stage of development suggests that this gene is up-regulated during the late preantral stage of development. Clearly, as with other species (Saunders et al. 2000), small non-growing and growing follicles can respond to oestrogens in sheep. However, the role of oestrogens in regulating early follicular growth has yet to be clearly defined (Palter et al. 2001, Fortune 2003).
Similar to what has been reported in other species (Saunders et al. 2000, Cardenas & Pope 2002, Hampton et al. 2004), expression of AR protein was observed in granulosa cells of type-2 follicles with consistent expression of both mRNA and protein for AR observed in granulosa and theca of type-3 and larger follicles. Some studies have also reported expression of AR in oocytes (Cardenas & Pope 2002, Szoltys et al. 2003); however, our results for the presence of AR in ovine oocytes were equivocal. Recent reports have indicated a stimulatory role for androgens in regulating the growth of pre-antral and small antral follicles in monkeys, mice and humans (reviewed in Fortune 2003, Jonard & Dewailly 2004). Based on the expression pattern of ARs, our results are not inconsistent with a similar role in sheep.
It is possible that progesterone has some regulatory influences in small ovine follicles as the theca expressed PR mRNA, as did granulosa cells of some type-4 (large pre-antral) and type-5 (antral) follicles. Since PR protein was detectable in the theca, but not granulosa cells, it might be that these two cell types express different isoforms (Conneely et al. 2003). The antibody utilised for immunohistochemistry in the present study only detected the B form of the receptors; and thus if the granulosa cells only expressed the A form, this would explain the apparent dichotomy between the in situ hybridisation and immunohistochemistry results. However, the differences between the localisation of PR mRNA and protein could also be related to differences in the sensitivities of the methodologies employed for detection. The high level of non-specific staining observed with the immunohistochemistry method may have masked low levels of specific staining for PR in some ovarian cells. Expression of PR has been observed in the theca cells of pre-antral and antral follicles, and corpora lutea of several species (Suzuki et al. 1994, Van den Broeck et al. 2002). However, expression in granulosa cells was much more variable, with PR protein being observed in bovine (Van den Broeck et al. 2002) but not ovine (the present study) or human granulosa cells (Suzuki et al. 1994).
All four steroid receptors were observed in stromal cells in neonatal and adult ovary. Expression of steroid receptors in the stroma tissue around small growing follicles has also been consistently observed in other species (Suzuki et al. 1994, Tomanek et al. 1997, Saunders et al. 2000, Cardenas & Pope 2002, Van den Broeck et al. 2002). In particular, strong expression of both forms of the ER as well as the AR was observed around clusters of small non-growing and small growing follicles. Thus, oestrogen and androgens may regulate small ovine follicles indirectly by regulating the stromal cell–follicular interactions as well as through direct regulation of follicular cells. One potential mechanism by which steroids may indirectly regulate early follicular growth through interaction with the stromal cells is through regulation of vascularisation of the small growing follicle (Dubey et al. 2000).
In conclusion, expression of receptors for steroid hormones was observed in the developing ovary and in small growing follicles. In particular, ERß was highly expressed in granulosa and germ cells before, during and after follicular formation. Expression of AR and ER was also observed in some cells of the developing gonad. In addition, ER, AR and PR were also expressed in small growing follicles in a developmental stage- and cellular type-specific manner. Thus, steroid hormones have the potential to regulate many aspects of ovarian function including development of the ovary, the formation of the follicle and early follicular growth in sheep.
|
Acknowledgements |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionAcknowledgementsReferences |
|---|
and PR cDNAs. The authors would also like to thank Norma Hudson, Anne O’Connell, Doug Jensen and Peter Smith for help with collection of tissues; Lee-Ann Still and Lynn O’Donovan for preparation of tissue sections; Anita Burgess and Tracy Scott for technical assistance; and Alan Barkus for help with preparation of photographs. |
Footnotes |
|---|
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionAcknowledgementsReferences |
|---|
Abbott DH, Dumesic DA & Franks S 2002 Developmental origin of polycystic ovary syndrome - a hypothesis. Journal of Endocrinology 174 1–5.[Abstract]
Bai W, Oliveros-Saunders B, Wang Q, Acevedo-Duncan ME & Nicosia SV 2000 Estrogen stimulation of ovarian surface epithelial cell proliferation. In Vitro Cellular and Developmental Biology. Animal 36 657–666.[CrossRef]
Britt KL, Drummond AE, Cox VA, Dyson M, Wreford NG, Jones ME, Simpson ER & Findlay JK 2000 An age-related ovarian phenotype in mice with targeted disruption of the Cyp 19 (aromatase) gene. Endocrinology 141 2614–2623.
Britt KL, Saunders PK, McPherson SJ, Misso ML, Simpson ER & Findlay JK 2004 Estrogen actions on follicle formation and early follicle development. Biology of Reproduction 71 1712–1723.
Cardenas H & Pope WF 2002 Androgen receptor and follicle-stimulating hormone receptor in the pig ovary during the follicular phase of the estrous cycle. Molecular Reproduction and Development 62 92–98.[CrossRef][ISI][Medline]
Cardenas H, Burke KA, Bigsby RM, Pope WF & Nephew KP 2001 Estrogen receptor beta in the sheep ovary during the estrous cycle and early pregnancy. Biology of Reproduction 65 128–134.
Conneely OM, Mulac-Jericevic B & Lydon JP 2003 Progesterone-dependent regulation of female reproductive activity by two distinct progesterone receptor isoforms. Steroids 68 771–778.[CrossRef][ISI][Medline]
Couse JF & Korach KS 1999 Estrogen receptor null mice: what have we learned and where will they lead us? Endocrine Reviews 20 358–417.
Dominguez MM, Liptrap RM & Basrur PK 1988 Steroidogenesis in fetal bovine gonads. Canadian Journal of Veterinary Research 52 401–406.[Medline]
Drummond AE, Britt KL, Dyson M, Jones ME, Kerr JB, O’Donnell L, Simpson ER & Findlay JK 2002 Ovarian steroid receptors and their role in ovarian function. Molecular and Cellular Endocrinology 191 27–33.[CrossRef][ISI][Medline]
Dubey RK, Rosselli M, Imthurn B, Keller PJ & Jackson EK 2000 Vascular effects of environmental oestrogens: implications for reproductive and vascular health. Human Reproduction Update 6 351–363.
Fortune JE 2003 The early stages of follicular development: activation of primordial follicles and growth of preantral follicles. Animal Reproduction Science 78 135–163.[CrossRef][ISI][Medline]
George F & Wilson J 1994 Sex determination and differentiation. In The Physiology of Reproduction, 2nd edn, pp 3–28. Eds E Knobil & JD Neill. New York: Raven Press.
Greco TL & Payne AH 1994 Ontogeny of expression of the genes for steroidogenic enzymes P450 side-chain cleavage, 3 beta-hydroxy-steroid dehydrogenase, P450 17 alpha-hydroxylase/C17-20 lyase, and P450 aromatase in fetal mouse gonads. Endocrinology 135 262–268.[Abstract]
Hampton JH, Manikkam M, Lubahn DB, Smith MF & Garverick HA 2004 Androgen receptor mRNA expression in the bovine ovary. Domestic Animal Endocrinology 27 81–88.[CrossRef][ISI][Medline]
Jansen HT, West C, Lehman MN & Padmanabhan V 2001 Ovarian estrogen receptor-beta (ERbeta) regulation: I. Changes in ERbeta messenger RNA expression prior to ovulation in the ewe. Biology of Reproduction 65 866–872.
Jonard S & Dewailly D 2004 The follicular excess in polycystic ovaries, due to intra-ovarian hyperandrogenism, may be the main culprit for the follicular arrest. Human Reproduction Update 10 107–117.
Juengel JL, Sawyer HR, Smith PR, Quirke LD, Heath DA, Lun S, Wakefield SJ & McNatty KP 2002 Origins of follicular cells and ontogeny of steroidogenesis in ovine fetal ovaries. Molecular and Cellular Endocrinology 191 1–10.[CrossRef][ISI][Medline]
Koering MJ, Danforth DR & Hodgen GD 1994 Early follicle growth in the juvenile macaca monkey ovary: the effects of estrogen priming and follicle-stimulating hormone. Biology of Reproduction 50 686–694.[Abstract]
Lun S, Smith P, Lundy T, O’Connell A, Hudson N & McNatty KP 1998 Steroid contents of and steroidogenesis in vitro by the developing gonad and mesonephros around sexual differentiation in fetal sheep. Journal of Reproduction and Fertility 114 131–139.[Abstract]
Lundy T, Smith P, O’Connell A, Hudson NL & McNatty KP 1999 Populations of granulosa cells in small follicles of the sheep ovary. Journal of Reproduction and Fertility 115 251–262.[Abstract]
Lydon JP, DeMayo FJ, Conneely OM & O’Malley BW 1996 Reproductive phenotpes of the progesterone receptor null mutant mouse. Journal of Steroid Biochemistry and Molecular Biology 56 67–77.[CrossRef][ISI][Medline]
Mauleon P, Bezard J & Terqui M 1977 Very early and transient 17b-estradiol secretion by fetal sheep ovary. In vitro study. Annales de Biologie Animale, Biochimie, Biophysique 17 399–401.[ISI]
Murdoch WJ & Van Kirk EA 2002 Steroid hormonal regulation of proliferative, p53 tumor suppressor, and apoptotic responses of sheep ovarian surface epithelial cells. Molecular and Cellular Endocrinology 186 61–67.[CrossRef][ISI][Medline]
Palter SF, Tavares AB, Hourvitz A, Veldhuis JD & Adashi EY 2001 Are estrogens of import to primate/human ovarian folliculogenesis? Endocrine Reviews 22 389–424.
Pentikainen V, Erkkila K, Suomalainen L, Parvinen M & Dunkel L 2000 Estradiol acts as a germ cell survival factor in the human testis in vitro. Journal of Clinical Endocrinology and Metabolism 85 2057–2067.
Pepe GJ, Billiar RB, Leavitt MG, Zachos NC, Gustafsson JA & Albrecht ED 2002 Expression of estrogen receptors alpha and beta in the baboon fetal ovary. Biology of Reproduction 66 1054–1060.
Quirke LD, Juengel JL, Tisdall DJ, Lun S, Heath DA & McNatty KP 2001 Ontogeny of steroidogenesis in the fetal sheep gonad. Biology of Reproduction 65 216–228.
Saunders PT, Millar MR, Williams K, Macpherson S, Harkiss D, Anderson RA, Orr B, Groome NP, Scobie G & Fraser HM 2000 Differential expression of estrogen receptor-alpha and -beta and androgen receptor in the ovaries of marmosets and humans. Biology of Reproduction 63 1098–1105.
Sawyer HR, Smith P, Heath DA, Juengel JL, Wakefield SJ & McNatty KP 2002 Formation of ovarian follicles during fetal development in sheep. Biology of Reproduction 66 1134–1150.
Shemesh M 1980 Estradiol-17 beta biosynthesis by the early bovine fetal ovary during the active and refractory phases. Biology of Reproduction 23 577–582.[Abstract]
Smith P, O WS, Hudson NL, Shaw L, Heath DA, Condell L, Phillips DJ & McNatty KP 1993 Effects of the Booroola gene (FecB) on body weight, ovarian development and hormone concentrations during fetal life. Journal of Reproduction and Fertility 98 41–54.[Abstract]
Suzuki T, Sasano H, Kimura N, Tamura M, Fukaya T, Yajima A & Nagura H 1994 Immunohistochemical distribution of progesterone, androgen and oestrogen receptors in the human ovary during the menstrual cycle: relationship to expression of steroidogenic enzymes. Human Reproduction 9 1589–1595.
Szoltys M, Slomczynska M & Tabarowski Z 2003 Immunohistochemical localization of androgen receptor in rat oocytes. Folia Histochemica et Cytobiologica 41 59–64.[Medline]
Tisdall DJ, Fidler AE, Smith P, Quirke LD, Stent VC, Heath DA & McNatty KP 1999 Stem cell factor and c-kit gene expression and protein localization in the sheep ovary during fetal development. Journal of Reproduction and Fertility 116 277–291.[Abstract]
Tomanek M, Pisselet C, Monget P, Madigou T, Thieulant ML & Monniaux D 1997 Estrogen receptor protein and mRNA expression in the ovary of sheep. Molecular Reproduction and Development 48 53–62.[CrossRef][ISI][Medline]
Van den Broeck W, D’Haeseleer M, Coryn M & Simoens P 2002 Cell-specific distribution of progesterone receptors in the bovine ovary. Reproduction in Domestic Animals 37 314–320.[CrossRef][ISI][Medline]
Weniger JP 1990 Aromatase activity in fetal gonads of mammals. Journal of Developmental Physiology 14 303–306.[ISI][Medline]
Wright JW, Toth-Fejel S, Stouffer RL & Rodland KD 2002 Proliferation of rhesus ovarian surface epithelial cells in culture: lack of mitogenic response to steroid or gonadotropic hormones. Endocrinology 143 2198–2207.
Yeh S, Tsai MY, Xu Q, Mu XM, Lardy H, Huang KE, Lin H, Yeh SD, Altuwaijri S, Zhou X, Xing L, Boyce BF, Hung MC, Zhang S, Gan L & Chang C 2002 Generation and characterization of androgen receptor knockout (ARKO) mice: an in vivo model for the study of androgen functions in selective tissues. PNAS 99 13498–13503.
Zachos NC, Billiar RB, Albrecht ED & Pepe GJ 2002 Developmental regulation of baboon fetal ovarian maturation by estrogen. Biology of Reproduction 67 1148–1156.
This article has been cited by other articles:
 |
|
 |
|
  A I Qureshi, S S Nussey, G Bano, P Musonda, S A Whitehead, and H D Mason Testosterone selectively increases primary follicles in ovarian cortex grafted onto embryonic chick membranes: relevance to polycystic ovaries Reproduction, August 1, 2008; 136(2): 187 - 194. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Hayashi, A. R O'Connell, J. L Juengel, K. P McNatty, G. H Davis, F. W Bazer, and T. E Spencer Postnatal uterine development in Inverdale ewe lambs Reproduction, March 1, 2008; 135(3): 357 - 365. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.A. Walters, C.M. Allan, and D.J. Handelsman Androgen Actions and the Ovary Biol Reprod, March 1, 2008; 78(3): 380 - 389. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Benoit, H. A. LaVoie, G. L. McCoy, and C. A. Blake Expression of Sperm Protein 22 (SP22) in the Rat Ovary During Different Reproductive States Experimental Biology and Medicine, July 1, 2007; 232(7): 910 - 920. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Steckler, M. Manikkam, E. K. Inskeep, and V. Padmanabhan Developmental Programming: Follicular Persistence in Prenatal Testosterone-Treated Sheep Is Not Programmed by Androgenic Actions of Testosterone Endocrinology, July 1, 2007; 148(7): 3532 - 3540. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.Y. Yang and J.E. Fortune Testosterone Stimulates the Primary to Secondary Follicle Transition in Bovine Follicles In Vitro Biol Reprod, December 1, 2006; 75(6): 924 - 932. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
