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Follicular development and its control.

The female reproductive cycle is based on a co-ordinated function of several regulatory elements and signalling systems. Of the approximately 7 million oocytes present in the human fetal ovary, only 475 will eventually ovulate. In the human, the development of a primordial follicle into a dominant one takes about 10 weeks. Approximately 300 follicles are recruited initially for growth and development, 30 of them are likely to become gonadotropin-dependent and enter competition for dominance and, finally, only one will achieve ovulation. The mechanisms by which follicle stimulating hormone, luteinizing hormone, growth factors and steroids may promote or disrupt follicular development are discussed in detail. Possible implications of these new facts on diagnosis and treatment of ovulatory disturbances are described.

Female↗

Inhibition of follicular development, vitellogenesis, and serum 17beta-estradiol concentrations in zebrafish following chronic, sublethal dietary exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

The environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent endocrine disruptor with the ability to affect several biologic processes, including reproduction. In fish, sublethal exposure to TCDD is known to modulate overall reproductive capacity, but impacts on follicular development and vitellogenesis are unknown. Here we show that chronic, dietary exposure to 0.08, 0.32, or 0.80 ng TCDD female(-1) day(-1) decreased egg production by more than 50% and that spawning success was reduced by as much as 96%. Serum estradiol concentrations were decreased more than twofold, accounting, in part, for observed decreases in serum vitellogenin concentrations by as much as 29%. Our data suggest that decreased egg production is likely the result of TCDD-mediated inhibition of the transition from pre-vitellogenic stage follicles to vitellogenic stage follicles, as well as the induction of follicular atresia. The majority of reproductive toxicity of TCDD is likely due to direct impacts on the ovary, yet histopathologic observations suggest liver toxicity could also contribute to observed impacts on vitellogenesis. Importantly, even when overall egg production is not significantly affected, our data show that subtle physiologic changes induced by TCDD can lead to altered gonadogenesis. This suggests that long-term exposure to very low concentrations of TCDD could greatly affect fecundity and reproductive success in fishes.

Animals↗

Elevated ovarian expression and serum concentration of alpha inhibin in the luteal phase during follicular development in the squirrel monkey (Saimiri boliviensis) compared to the human.

The goal of the present investigation was to determine in the squirrel monkey the source and pattern of inhibin, a hormone known to effect reproductive steroid levels via pituitary and ovarian mechanisms. Since this seasonally polyestrous species is known to have elevated serum levels of reproductive steroids compared to other primates, the levels of ovarian alpha subunit mRNA expression and serum total alpha inhibin, estradiol, progesterone, and luteinizing hormone were measured and compared to human levels. Expression of the alpha subunit was robust in monkey luteal tissue compared to expression in human luteal tissue. Squirrel monkey serum inhibin peaked 4 days after the luteinizing hormone surge and correlated with progesterone changes. These luteal serum levels of inhibin were greater than 12 times higher than the human levels yet bio-LH activities were less than in the human during the luteal phase. Inhibin concentrations during the nonbreeding season were generally half the levels measured in the breeding season and undetectable in ovariectomized animals. However, exogenous FSH stimulation induced a marked rise in inhibin, which correlated with an estradiol rise. In conclusion, abundant alpha inhibin subunit expression in the luteal ovary of the squirrel monkey and loss of serum delectability in ovariectomized animals indicates that the principle source of inhibin in the squirrel monkey is the ovary. Elevated serum inhibin levels during the luteal phase concurrent with ovulatory-size follicular development is unique among species studied thus far. Possible simultaneous inhibin production from both follicular and luteal tissue may be responsible for the exceptionally high inhibin levels.

Adult↗

FSH, LH and prolactin levels, ovarian follicular development and ovarian responsiveness to FSH in the Snell dwarf mouse.

The homozygous Snell dwarf mouse is sterile. It has been shown that pituitary hormone levels are low in 3 month old animals except for FSH and LH whose pituitary contents and plasma concentrations are normal. In this study, the pituitary FSH, LH and prolactin (Prl) content, the FSH plasma concentration and the ovarian follicular development of the Snell dwarf mouse were studied at 18, 20, 24, 40 and 80 days of age. Normal mice were also studied at the same age and served as controls. Pituitary FSH was significantly lower in dwarf mice compared with controls during the period days 18 to 30, while plasma FSH was significantly lower during the period days 20 to 80. Pituitary LH was significantly lower in dwarf mice during the period days 18 to 40. In normal mice, pituitary Prl increased with age, but remained consistently low in dwarf mice. The normal number of growing follicles was similar in dwarf mice and controls up to day 30, but thereafter the total number of growing follicles was greater in the controls. In the dwarf mice, the production of antral follicles was low and there were no ovulations. The rates of atresia were similar in the two genotypes. The responsiveness of the dwarf mouse ovary to FSH was then examined. When dwarf and control mice were supplemented with FSH for 5 days starting at 24 days of age, the ovarian and uterine weights increase 6- and 5-fold, respectively, in the dwarf mice, and 2- to 3-fold in the normal mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Multiple follicular development and ovarian steroidogenesis following subcutaneous administration of a highly purified urinary FSH preparation in pituitary desensitized women undergoing IVF: a multicentre European phase III study.

A multicentre, multinational study was carried out between November 1990 and February 1992 to assess the safety and efficacy of a new highly purified urinary human follicle stimulating hormone (FSH; Metrodin HP) which is practically devoid of luteinizing hormone (LH) activity. Metrodin HP was administered s.c. to stimulate multiple follicular development in women undergoing in-vitro fertilization (IVF) and embryo transfer. A total of 139 women were recruited from 10 participating centres. Of these, 135 underwent pituitary desensitization with a long gonadotrophin-releasing hormone (GnRH) agonist protocol and following determination of ovarian inactivity (mean +/- SD of 12.9 +/- 3.2 days), Metrodin HP s.c. stimulation was started; 122 patients were fully eligible for efficacy analysis and 118 of these (97%) received up to 10,000 IU human chorionic gonadotrophin (HCG) to induce final follicular maturation and timed oocyte recovery. Mean plasma LH concentrations at the beginning of Metrodin HP treatment were 1.6 +/- 0.8 mIU/ml and by the day of HCG administration were significantly (P < 0.001) reduced (1.2 +/- 0.8 mIU/ml). The mean plasma oestradiol and inhibin concentrations on the day of HCG were 6173 +/- 3567 pmol/l and 8.2 +/- 4.4 IU/ml respectively. There was a positive correlation (r = 0.49, P < 0.001) between individual oestradiol and inhibin concentrations on the day of HCG. In the 118 patients who received HCG, the mean number of oocytes recovered was 8.4 +/- 4.7 following stimulation with 36 +/- 10, 75 IU ampoules of Metrodin HP over 12.2 +/- 2.1 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Buserelin↗

Follicular development, steroidogenesis and gonadotrophin secretion in response to long-term treatment with a gonadotrophin-releasing hormone agonist in the rat.

Gonadotrophin-releasing hormone (GnRH) and its agonists are implicated in the local control of rat ovarian function. We have evaluated the effects of long-term administration of different doses of GnRH agonist (GnRH-Ag) in vivo (a) on reproductive cyclicity and follicular development, (b) on peripheral gonadotrophin and steroid concentrations and (c) on in vitro cAMP and progesterone production by the follicles in response to stimulatory doses of FSH or LH (1 microgram/ml). GnRH-Ag (0.2, 1 or 5 micrograms/day) administration for 28 days had a profound impact on the oestrous cycle of rats as revealed by vaginal cytology. GnRH-Ag treatment caused a decrease in ovarian and uterine weights, which correlated very well with the decrease in the number of follicles present in the ovary. GnRH-Ag (5 micrograms/day) reduced the number of early preantral follicles and there was complete disappearance of early as well as late antral follicles. However, a dose of 1 microgram GnRH-Ag/day was effective in the complete demise of only late antral follicles with a significant attenuation in the number of early antral follicles. There was an enhancement in serum LH concentrations in response to the highest dose of GnRH-Ag administration with serum FSH concentrations declining in rats treated with the two higher doses. However, serum prolactin concentrations were attenuated only in rats treated with the highest dose of GnRH-Ag. GnRH-Ag treatment decreased serum progesterone and oestradiol concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Regulatory system and physiological significance of local factors in the ovary during follicular development and maturation].

The concept of classical endocrine control of ovarian function has now been extended to a more complex regulator system, including paracrine and autocrine modulating mechanisms. Among many factors, locally produced intraovarian insulin-like growth factors (IGFs) and the binding proteins (IGFBPs) and renin-angiotensin system (RAS) have been shown to play an important role in the control of folliculogenesis and ovulation. Growth hormone (GH) amplified gonadotropin actions in the process of follicular development and ovulation, at least in part, stimulating ovarian IGF-I production. IGF-I as well as IGFBPs were produced by ovarian granulosa cells. IGF-I acted synergistically with gonadotropins in the stimulation of a variety of granulosa cell functions, including estradiol (E2) and progesterone production and plasminogen activator (PA) activity. Furthermore, rabbit ovarian cells and rat granulosa cells possessed specific IGF type I receptors. The biological effects of IGF-I, including intrafollicular PA activities and ovarian steroidogenesis, were modulated by a family of IGFBPs in a complex manner. In the ovary IGFBP-3 appeared to neutralize the actions of gonadotropin and IGF-I, probably via its ability to sequester IGF-I, in the process of follicular growth, oocyte maturation, and ovulation. A functional local RAS is also known to exist in the ovary. Angiotensin II (Ang II) at 2-h intervals induced oocyte maturation, ovulation, and the production of E2 and prostaglandins (PGs) in the in vitro perfused rabbit ovaries in the absence of gonadotropin. In addition, the intrafollicular Ang II content and renin-like activity were enhanced during the ovulatory process by exposure to hCG, and the concomitant addition of saralasin inhibited hCG-induced ovulation in a dose-dependent manner. Captopril, an inhibitor of angiotensin converting enzyme, significantly inhibited the resumption of meiosis in the ovulated ova and follicular oocytes stimulated by hCG. Autoradiographic study revealed that AT2 receptors were predominantly located in granulosa cells, whereas AT1 receptors were more concentrated in the stroma and the thecal layers. Ang II-stimulated production of E2 and PGs and ovulation were significantly blocked by PD123319, a selective nonpeptide antagonist for AT2 receptors. The increase in ovarian IGF-I synthesis by exposure to hCG or GH induced the stimulation of intrafollicular PA activities. IGFBP-3 blocked the stimulatory effects of gonadotropin in the ovulatory process by neutralizing endogenously produced IGF-I, resulting in reduced intrafollicular PA activities. The increase in intrafollicular PA activities significantly stimulated the generation of Ang II in the preovulatory follicles by an activation of prorenin to renin and/or by the direct cleavage of angiotensinogen.(ABSTRACT TRUNCATED AT 400 WORDS)

Angiotensin II↗

ADAMTS-1 is involved in normal follicular development, ovulatory process and organization of the medullary vascular network in the ovary.

To clarify the role of disintegrin-like and metalloproteinase with thrombospondin type I motifs-1 (ADAMTS-1) in ovarian function, we examined abnormalities in ovulatory processes, folliculogenesis and the vascular system of ADAMTS-1 null ovaries. First, when immature female mice were treated with pregnant mare serum gonadotropin (PMSG)/human chorionic gonadotropin (hCG), the number of ovulated oocytes was markedly decreased in ADAMTS-1 null mice in comparison to ADAMTS-1 (+/-) controls. The proportion of anovulated follicles to total mature follicles was significantly higher in ADAMTS-1 null females when compared with controls. The numbers of growing follicles at each stage were counted. The number of follicles at type 5b (late preantral) and later stages was markedly reduced in ADAMTS-1 null mice, irrespective of gonadotropin treatment (no gonadotropins, PMSG alone or PMSG/hCG). These data demonstrate that impairment of ovarian function to ovulate oocytes in ADAMTS-1 null mice occurs at two different levels: in the development of growing follicles and ovulatory processes. Furthermore, ADAMTS-1 null ovaries included a number of unusual atretic follicles that showed no sign of oocyte degeneration but lost the surrounding granulosa cell layers and were considered to be derived from type 4 or 5a follicles. These results suggest that ADAMTS-1 is important for follicular development beyond the type 4 and/or 5a and for maintaining normal granulosa cell layers in follicles. Finally, the number of large blood vessels in the medullar zone was significantly decreased in ADAMTS-1 null mice ovaries, suggesting that ADAMTS-1 is also involved in the organization of the medullary vascular network.

ADAM Proteins↗

Regulation of prohibitin expression during follicular development and atresia in the mammalian ovary.

Prohibitin is a ubiquitous and highly conserved protein implicated as an important regulator in cell survival. Prohibitin content is inversely associated with cell proliferation, but it increases during granulosa cell differentiation as well as in earlier events of apoptosis in a temperature-sensitive granulosa cell line. In the present study, we have characterized the spatial expression patterns for prohibitin using established in vivo models for the induction of follicular development and atresia in the mammalian ovary. Comparative Western blot analyses of granulosa cell lysates from control ovaries and from ovaries primed with eCG or treated with eCG plus anti-eCG (gonadotropin withdrawal) were conducted. Prohibitin was immunolocalized in rat ovarian sections probed with antibodies against either proliferating cell nuclear antigen (PCNA) or cholesterol side-chain cleavage cytochrome P450 (P450(scc)) or in terminal deoxynucleotidyl transferase-mediated dUTP nick end labeled sections. Additionally, porcine oocytes, zygotes, and blastocyts were also immunolocalized with prohibitin antibody. Immunolocalization revealed the presence of prohibitin in granulosa cells, theca-interstitial cells, and the oocyte. The results indicate that prohibitin protein expression in the gonadotropin-treated cells was upregulated. Immunoreactivity of prohibitin was inversely related to PCNA expression during follicular maturation and colocalized with P450(scc). Prohibitin appeared to be translocated from the cytoplasm to the nucleus in atretic follicles, germinal vesicle-stage oocytes, zygotes, and blastocysts. These results suggest that prohibitin has several functional regulatory roles in granulosa and theca-interstitial cells and in the ovum during follicular maturation and atresia. It is likely that prohibitin may play an important role in determining the fate of these cells and eventual follicular destiny.

Animals↗

Impairment of follicular development by intra-ovarian infusion of gonadotrophin-releasing hormone antiserum in prepubertal pigs.

Antiserum against gonadotrophin-releasing hormone (GnRH) was infused into one ovary in 4 prepubertal gilts and control porcine serum was infused into one ovary in 4 other gilts. Ovaries were infused for 156 h, after which infused and non-infused ovaries were removed surgically and processed for histology. Infusion of GnRH antibodies did not alter (P greater than 0.10) concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH) or oestradiol-17 beta, and GnRH titres in peripheral circulation were low, averaging 1:15. Weights of ovaries not infused were similar (P greater than 0.10) between treatment groups. There were fewer (P less than 0.05) follicles greater than 0.5 mm in diameter in the ovaries infused with GnRH antiserum than in the others, but there were no differences (P greater than 0.10) between treatment groups in the number of follicles less than 0.5 mm in diameter. Infusion of GnRH antibodies increased (P less than 0.05) the incidence of atresia in follicles with greater than 4 layers of granulosa cells compared with the other treatment groups. These results provide evidence that a peptide binding to the GnRH antibodies is involved directly in ovarian follicular development.

Animals↗

A bolus of recombinant human follicle stimulating hormone at midcycle induces periovulatory events following multiple follicular development in macaques.

The efficacy of follicle stimulating hormone (FSH) as an alternative to luteinizing hormone (LH)/human chorionic gonadotrophin (HCG) for the initiation of periovulatory events in primate follicles is unknown. A single bolus of 2500 IU recombinant (r)-hFSH was compared to 1000 IU r-HCG for its ability to promote oocyte nuclear maturation and fertilization, granulosa cell luteinization and corpus luteum function following r-hFSH (60 IU/day) induction of multiple follicular development in rhesus monkeys. Following the r-hFSH bolus, bioactive luteinizing hormone concentrations were <3 ng/ml. Peak concentrations of serum FSH (1455+/-314 mIU/ml; mean+/-SEM) were attained 2-8 h after r-hFSH, and declined by 96 h. Bioactive HCG concentrations peaked between 2-8 h after r-HCG and remained > or = 100 ng/ml for >48 h, while immunoreactive FSH concentrations were at baseline. The proportion of oocytes resuming meiosis and undergoing in-vitro fertilization (IVF) were comparable for r-hFSH (89%; 47+/-19%) and r-HCG (88%; 50+/-17%). In-vitro progesterone production and expression of progesterone receptors in granulosa cells did not differ between groups. Peak concentrations of serum progesterone in the luteal phase were similar, but were lower 6-9 days post-FSH relative to HCG. Thus, a bolus of r-hFSH was equivalent to r-HCG for the reinitiation of oocyte meiosis, fertilization and granulosa cell luteinization, but a midcycle FSH surge did not sustain normal luteal function in primates.

Animals↗

Evaluation of diagnostic ultrasound as a parameter of follicular development in an in vitro fertilization program.

The ultrasound results in 141 patients through 203 cycles stimulated with clomiphene citrate prior to oocyte collection and in vitro fertilization are analyzed. A wide range in the size and number of follicles was seen. Bivariate analysis of the size of the largest follicle, compared with the time of the spontaneous luteinizing hormone (LH) surge, has shown a highly significant correlation (r = 0.720; P less than 0.001) between these two variables, but the accuracy of prediction of the LH surge in a specific cycle, as expressed by the standard error of estimate, was 34.3 hours. As an isolated observation, ultrasound results are no better than the menstrual history in predicting the time of the LH surge in stimulated cycles. Multiparameter assessment of follicular development is required.

Chorionic Gonadotropin↗

The effectiveness and safety of recombinant human LH to support follicular development induced by recombinant human FSH in WHO group I anovulation: evidence from a multicentre study in Spain.

BACKGROUND: Until recently, human menopausal gonadotrophin (HMG), a urinary extract containing a fixed combination of LH and FSH, was the only source of exogenous LH for women with hypogonadotrophic hypogonadism undergoing ovulation induction with gonadotrophins. Recombinant human LH (rLH) is now available for clinical use, providing a new treatment option but clinical data on its use are scanty. Therefore, the aim of the present study was to investigate the efficacy and safety of rLH combined with recombinant FSH (rFSH) to induce follicular development and ovulation in World Health Organization (WHO) group I anovulatory women. METHODS: We included in this multicentre study 38 hypogonadotrophic anovulatory (WHO group I) women. Patients received 150 IU/day rFSH and 75 IU/day rLH (with the possibility of dose adjustment) as a single s.c. injection for up to three cycles with a total of 84 treatment cycles. RESULTS: Sufficient follicular growth was observed in 79 (94%) out of 84 initiated cycles. The 75 IU rLH dose was found to be effective in most treatment cycles (94%) and only five cycles in three patients required daily dose increase. Overall, HCG was administered to trigger ovulation in 67 (80%) of the 84 cycles while it was withheld in 12 cycles (14%) due to ovarian hyper-response and five cycles (6%) were cancelled for insufficient follicular growth. The pregnancy rate per started treatment cycle and per cycle given HCG was 18 and 22.4% respectively. Pregnancy was achieved by 15 (39.5%) of the 38 patients. Mild to moderate ovarian hyperstimulation syndrome occurred in three patients. Local tolerance was good. CONCLUSIONS: This study confirms that combined rFSH and rLH treatment induces follicular growth, ovulation and pregnancy in a good proportion of hypogonadotrophic anovulatory patients and is well tolerated. The doses of 150 IU rFSH and 75 IU rLH daily seem the most appropriate but in a small minority of patients doses >75 IU rLH/day may be necessary.

Adult↗

Effects of oral contraceptives administered at defined stages of ovarian follicular development.

OBJECTIVE: To elucidate the effects of initiating oral contraceptives (OC) at defined stages of ovarian follicle development. DESIGN: Prospective longitudinal study. SETTING: Healthy volunteers in an academic research environment. PATIENT(S): Forty-five healthy women between the ages of 18 and 35 years, randomized to initiate OC when a follicle diameter of 10, 14, or 18 mm was first detected. INTERVENTION(S): The OC administration at defined stages of dominant follicle development. MAIN OUTCOME MEASURE(S): Fates of all dominant follicles and serum concentrations of E(2)-17beta, LH, and P before and after initiating OC. RESULT(S): No ovulations (0/16) were observed when OC use was initiated at a follicle diameter of 10 mm, 4/14 (29%) follicles ovulated when OC were initiated at 14 mm, and 14/15 (93%) ovulated when OC were initiated at 18 mm. When ovulation did not occur, follicles regressed or became anovulatory cysts. Peak LH and E(2) levels were lowest in the 10-mm group, moderate in the 14-mm group, and greatest in the 18-mm group. Peak endocrine levels in all treatment groups were lower than the historic reference group. CONCLUSION(S): Follicular development, ovulation, and endocrine concentrations were not suppressed effectively when OC were initiated at late stages of dominant follicle development.

Adolescent↗

Gene-knockout mice with abnormal epidermal and hair follicular development.

In the past 8 years, analysis of mutant mice and development of gene-knockout mice have provided important new avenues to identify disease genes and to study gene functions in the skin. Targeted disruption of genes in mice is a powerful means to investigate the contribution of a particular gene defect to a given phenotype and to generate murine models of hereditary skin disorders with epidermal and hair follicular abnormalities. This review summarizes recent studies of knockout mouse models with abnormalities in epidermal and/or hair follicular development.

Animals↗

Follicular development in spontaneous and stimulated cycles in women with minimal-mild endometriosis.

OBJECTIVE: To study follicle development in women with minimal-mild endometriosis. DESIGN: In women with endometriosis a spontaneous ovulatory cycle was compared with two subsequent cycles in which either clomiphene or clomiphene and FSH were given to stimulate folliculogenesis. Spontaneous cycles in women with tubal infertility provided a comparison group. SETTING: Infertility clinic, Aberdeen Maternity Hospital. SUBJECTS: 17 women with minimal-mild endometriosis and 10 women with tubal infertility. INTERVENTIONS: The women with endometriosis were treated with 150 mg clomiphene citrate from days 2 to 6 in one cycle and in a subsequent cycle with 150 mg clomiphene citrate on days 2 to 6 plus 75 iu FSH daily thereafter. MAIN OUTCOME MEASURES: Follicular size measured daily using ultrasound. Serum FSH estimated on days 5 and 7 and then daily. RESULTS: Spontaneous follicular growth in the women with endometriosis was similar to that in the women with tubal infertility. Follicular development began earlier in cycles with clomiphene/FSH and the leading follicle reached 16 mm 2 days sooner but the rate of growth was similar whether or not either regimen of stimulation was used. CONCLUSION: Follicular growth is not impaired by minimal-mild endometriosis. Infertility with this condition cannot be explained by altered follicular growth or responsiveness.

Adult↗

Effect of cyclofenil on hormonal dynamics, follicular development and cervical mucus in normal and oligomenorrhoeic women.

Cyclofenil is a triphenylethylene derivative, similar in structure to clomiphene citrate, which is used to induce ovulation in anovulatory women. The effects of cyclofenil on a group of 10 normal cyclic and 10 oligomenorrhoeic subjects were examined in a double blind controlled cross-over study. Both groups of women were administered either cyclofenil or, following a washout cycle, a placebo in two treatment cycles. Urinary oestrone and pregnanediol excretion were measured daily and ultrasound scans performed to assess follicular development. Frequent sampling of blood was performed on day 6 to study luteinizing hormone (LH) and follicle stimulating hormone (FSH) pulsatile release. Cervical mucus changes and sperm-cervical mucus interaction were studied after identification of the LH peak. There were no significant differences between cyclofenil and placebo cycles in the following: ovulation rates, daily urinary oestrone and pregnanediol excretion, the number or size of developing follicles, LH pulsatility (parameters studied: number of peaks, pulse interval, pulse amplitude, pulse area and mean nadir LH), mean FSH level on day 6, cervical mucus and sperm-cervical mucus interaction. In view of our inability to demonstrate an effect on any parameter of endocrine function in normal and oligomenorrhoeic women, these results throw doubt on the therapeutic value of cyclofenil in its present dosage and formulation.

Adult↗

Alkaline phosphatase activity in the theca of ovarian follicles of the hen throughout follicular development.

Within the hen's ovary, the theca tissue of small follicles that have not yet entered the preovulatory hierarchy is a major contributor to ovarian steroidogenesis. Relatively little is known about developmental stages in the theca layer within this pool of follicles and of the histological properties of this tissue. In pigs and sheep, alkaline phosphatase activity has been identified in the theca of preovulatory follicles and in theca-derived cells in the corpus luteum. The objectives of this study were to document morphological changes in the theca layer through pre- and postovulatory follicular development, and to assess alkaline phosphatase activity at these developmental stages. Ovarian tissue containing small white, large white, small yellow, large yellow, and postovulatory follicles (POF) was obtained from mature White Leghorn hens and embedded in either methacrylate for morphological assessment or paraffin for alkaline phosphatase histochemistry. Alkaline phosphatase activity was found to be specific for cells of the theca interna in preovulatory follicles. Activity was first detectable in very small white follicles, the earliest stage in which the theca interna could be distinguished from the theca externa, and highest in the yellow yolky follicles. After ovulation, activity decreased to undetectable levels by the POF4 to 5 stages in POF within 4 to 5 d after ovulation. This study has shown that in the domestic hen, alkaline phosphatase activity is present in cells adjacent to the basal lamina of the theca interna of preovulatory follicles and POF up to 4 to 5 d after ovulation. Identification of the functional significance of this histological reaction will provide new information on ovarian function in the hen.

Alkaline Phosphatase↗