Ovarian volume and antral follicle counts as indicators of menopausal status.

Objective: Recent studies suggest that ovarian volume and antral follicle numbers may be sensitive, specific, and early indicators of menopausal status. The accuracy of these markers, however, has not been compared directly to more traditional markers [age and follicle-stimulating hormone (FSH) levels]. Thus, the purpose of this study was to test whether ovarian volume and antral follicle counts are more sensitive and specific markers of menopausal status than age or FSH levels.

Nerve growth factor is required for early follicular development in the mammalian ovary.

Nerve growth factor (NGF) epitomizes a family of proteins known as the neurotrophins (NTs), which are required for the survival and differentiation of neurons within both the central and peripheral nervous system. Synthesis of NGF in tissues innervated by the peripheral nervous system is consistent with its function as a target-derived trophic factor. However, the presence of low- and high-affinity NGF receptors in the gonads suggests another function for the NTs within the reproductive endocrine system.

Effect of bcl-2 on the primordial follicle endowment in the mouse ovary.

Little is known about the embryonic factors that regulate the size of the primordial follicle endowment at birth. A few studies suggest that members of the B-cell lymphoma/leukemia-2 (bcl-2) family of protooncogenes may be important determinants. Thus, the purpose of this study was to test whether bcl-2 regulates the size of the primordial follicle pool at birth.

Using women's health research to develop women leaders in academic health sciences: the National Centers of Excellence in Women's Health.

While the number of women entering U.S. medical schools has risen substantially in the past 25 years, the number of women in leadership positions in academic medicine is disproportionately small.

Gestational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin induces developmental defects in the rat vagina.

At puberty, female rats exposed in utero to 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) exhibit a persistent thread of mesenchymal tissue surrounded by keratinized epithelium that partially occludes the vaginal opening. Our objective was to determine the earliest time during fetal development that morphological signs of this vaginal canal malformation could be detected and to obtain greater insight into mechanisms involved in this effect. Pregnant rats were administered a single dose of vehicle (control) or TCDD (1.

Workshop to identify critical windows of exposure for children's health: reproductive health in children and adolescents work group summary.

This work group report addresses the central question: What are the critical windows during development (preconception through puberty) when exposure to xenobiotics may have the greatest adverse impact on subsequent reproductive health? The reproductive system develops in stages, with sex-specific organogenesis occurring prenatally and further maturational events occurring in the perinatal period and at puberty. Complex endocrine signals as well as other regulatory factors (genetics, growth factors) are involved at all stages. Evidence from animal models and human studies indicates that many specific events can be perturbed by a variety of toxicants, with endocrine-mediated mechanisms being the more widely studied.

Ovarian volume and menopausal status.

Objective: The purposes of this study were to (1) examine whether ovarian volume differs by age and menopausal status in healthy women; (2) evaluate whether ovarian volume could be a sensitive and specific predictor of menopausal status; and (3) assess whether ovarian volume is affected by cigarette smoke, oral contraceptives (OCs), and hormone replacement therapy (HRT).

Design: Each participant (527 women) completed an extensive in-home interview that assessed age, menopausal status, smoking history, OC use, and HRT use. Each participant also received a transvaginal ultrasound that measured ovarian volume.

90-day feeding and one-generation reproduction study in Crl:CD BR rats with 17 beta-estradiol.

Over the past several years, there has been increasing concern that chemicals and pesticides found in the environment may mimic endogenous estrogens, potentially producing adverse effects in wildlife and human populations. Because estrogenicity is one of the primary concerns, a 90-day/one-generation reproduction study with 17 beta-estradiol was designed to set dose levels for future multigenerational reproduction and combined chronic toxicity/oncogenicity studies. The purpose of these studies is to evaluate the significance of a range of responses as well as to provide benchmark data for a risk assessment for chemicals with estrogen-like activities.

In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces genital dysmorphogenesis in the female rat.

Recently, Gray and Ostby (Toxicol. Appl. Pharmacol.

Chronically elevated luteinizing hormone depletes primordial follicles in the mouse ovary.

A few years before reproductive senescence, primordial follicles are depleted from the ovary at a dramatically accelerated rate. It has been proposed that this depletion is due to transient increases in gonadotropin levels. To test this hypothesis, we used mice that produce chronically elevated levels of serum LH via expression of an LHbeta subunit transgene.

Elevated luteinizing hormone in prepubertal transgenic mice causes hyperandrogenemia, precocious puberty, and substantial ovarian pathology.

In women, chronically elevated androgens have been associated with polycystic ovarian syndrome and infertility. Recently, we described transgenic mice with elevated serum LH secondary to targeted expression of a transgene encoding a chimeric LH beta-subunit. Mature transgenic females exhibit elevated androgens, anovulation, and a range of ovarian phenotypes including cysts, widespread luteinization, and tumors.

Overview of ovarian follicular development: considerations for the toxicologist.

Folliculogenesis is the lengthy process that results in the production of a species-specific, highly consistent number of follicles, which ripen during each reproductive cycle at precisely the appropriate time for ovulation. Certain features of folliculogenesis may have special implications for toxicologists studying effects of environmental mutagens on oocytes. Such features include the constantly changing geometry of the ovarian follicle, the great excess of developing follicles (most of which will degenerate rather than ovulate), the exponential nature of follicular growth, the acceleration of cell proliferation as follicular size increases, and the location of the principal feedback regulatory step at the penultimate stage of the developmental process.

Patterns of ovarian cell proliferation in rats during the embryonic period and the first three weeks postpartum.

The purpose of this study was to characterize the patterns of ovarian cell proliferation during the earliest stages of folliculogenesis, which occur in the embryonic period and the first weeks postpartum in rats. Rats were given continuous infusions of [3H]thymidine (3H-TdR) or bromodeoxyuridine (BrdU), and cells that were synthesizing DNA were visualized by autoradiography or immunohistochemistry. There were dramatic changes in the patterns of cell proliferation during the period studied.

Interleukin-1 beta-converting enzyme-related proteases (IRPs) and mammalian cell death: dissociation of IRP-induced oligonucleosomal endonuclease activity from morphological apoptosis in granulosa cells of the ovarian follicle.

The Caenorhabditis elegans death susceptibility gene, ced-3, has a number of homologs in vertebrate species, including interleukin-1 beta (IL-1 beta)-converting enzyme (ICE), Ich-1long, and CPP32. These genes, which encode a family of related proteases, have been shown to induce apoptosis when transfected into eukaryotic cells. However, it remains to be determined whether these proteases are involved in apoptotic cell death under physiological conditions.

Expression of neurotrophins and their receptors in the mammalian ovary is developmentally regulated: changes at the time of folliculogenesis.

An emerging body of evidence suggests that neurotrophins not only promote neuronal survival and differentiation, but can also target nonneuronal cells for their actions. Neurotrophins initiate their biological effects by binding to cell membrane tyrosine kinase receptors of the trk protooncogene family. In addition, all neurotrophins recognize with similar affinity a different receptor molecule known as p75 nerve growth factor receptor (p75 NGFR) or low affinity NGFR, which appears to interact with the trk receptors to potentiate their response to neurotrophins.

Vasoactive intestinal peptide-mediated suppression of apoptosis in the ovary: potential mechanisms of action and evidence of a conserved antiatretogenic role through evolution.

Vasoactive intestinal peptide (VIP)-containing nerve fibers are present in ovarian follicles at all stages of development, and VIP, acting primarily via the cAMP pathway, has been reported to modulate many aspects of granulosa cell function. Herein we examined the effects of VIP and its potential mechanisms of action on apoptosis in antral follicles isolated from ovaries of gonadotropin-primed immature rats and incubated in vitro under serum-free conditions. Additionally, the effects of VIP on apoptosis in isolated avian granulosa cells incubated in vitro were used as a comparative model system to determine whether the ability of VIP to modulate apoptosis in the ovary has been conserved through evolution.

Relationship between the supply of primordial follicles and the onset of follicular growth in rats.

Primordial follicles enter a state of suspended animation when they are formed and constitute a "stockpile" from which all growing follicles are derived. The factors that release individual follicles from their quiescent state are unknown. Many investigators believe that the number of follicles in the primordial stockpile is a major factor in determining the rate at which follicles begin to grow.

Heterogeneity of cell populations that contribute to the formation of primordial follicles in rats.

To study the events that lead to the formation of primordial follicles, pregnant rats were given continuous infusions of [3H]thymidine (3H-TdR) beginning on Days 14-19 of pregnancy (e14-e19) and continuing for 48-120 h. Ovaries from the pups were collected and plastic-embedded histological sections were prepared for autoradiography. The autoradiographs revealed that within the core of the developing ovary were a large number of cells that remained mitotically inactive (failed to incorporate label) from e14 through the day of birth.

The changing architecture of the neonatal rat ovary during histogenesis.

The purpose of this study was to describe the changing histological organization of the rat ovary during postpartum days one through three (p1-p3). A PC-based image-combining microscope system was used to reconstruct the ovary in three dimensions. On p1, cyclindrical pocket-like structures radiated from the core of the ovary that were open toward the surface epithelium.

Correlation of age-associated increases in follicle stimulating hormone secretion with decreases in antral follicles: failure of progesterone-induced acyclicity to prevent these changes.

It is well known that the number of follicles in the mammalian ovary decreases with age. In light of previous data from this laboratory showing age-related alterations in the secretion and production of follicle-stimulating hormone (FSH) in rats by 5-6 months of age, one objective of the present study was to determine if alterations in FSH secretion were accompanied by changes in the number of antral follicles. A second objective of this study was to determine whether or not interruption of cyclic activity by continuous progesterone (P) treatment could decelerate age-associated changes in FSH secretion possibly by retarding the depletion of follicles through ovulation.

Theca cells may be present at the outset of follicular growth.

Opinions differ concerning when theca cells arise during follicular growth. Theca cells cannot be distinguished from ovarian stroma cells on the basis of morphology alone. However, long-term continuous infusion of [3]thymidine (3H-TdR) thoroughly labels theca cells of large and medium-sized follicles whereas most stromal cells remain unlabeled.

Evidence for luteal cell hyperplasia during pregnancy.

The pronounced increase in luteal size and weight that occurs during rat pregnancy has been largely attributed to luteal cell hypertrophy. It is generally believed that hyperplasia does not play a role in luteal growth, since it is thought that luteal cell division in vivo does not occur. Recent data suggest that this may not be the case.