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PubMed1988

Lymphokines from concanavalin-A-stimulated lymphocytes regulate rat granulosa cell steroidogenesis in vitro.

Animals with impaired immune function show numerous reproductive disorders. To determine whether immune factors might play a direct role in the regulation of ovarian function, we examined the effects of Concanavalin-A-stimulated lymphocyte supernates (CAS) on steroidogenesis by cultured rat granulosa cells. Granulosa cells from immature estrogen-primed rats were incubated for 48 h with increasing doses of CAS in the presence or absence of FSH. In the absence of FSH, CAS produced a dose-dependent increase in progestin (progesterone and 20 alpha-hydroxyprogesterone) production to a maximum of 190-fold greater than untreated controls, but did not stimulate estrogen production. In the presence of FSH, the stimulatory effect of CAS on progestin production was additive with that of FSH. In contrast, CAS inhibited FSH-stimulated estrogen production in a dose-dependent manner. The maximum inhibition was greater than 90%. Addition of the phosphodiesterase inhibitor isobutylmethylxanthine to CAS-containing cultures significantly enhanced the stimulatory effect of CAS on progesterone production, suggesting that this action may be exerted through a cAMP-mediated pathway. The stimulatory component of CAS was heat labile, acid stable, and required a trypsin-sensitive cell surface recognition site, whereas the inhibitory component was both heat and acid stable. Neither the stimulatory nor the inhibitory actions of CAS were mimicked by treating granulosa cells with supernates from Concanavalin-A-stimulated neonatal cardiac or hepatic cell cultures. Thus, the present studies demonstrate that secretory products of lymphocytes (collectively termed lymphokines) can affect steroidogenesis in cultured rat granulosa cells. These data imply that immune cell factors may play a significant role in the differentiation and maturation of granulosa cells.

1-Methyl-3-isobutylxanthine↗

PubMed1999

The human growth hormone antagonist B2036 does not interact with the prolactin receptor.

The human growth hormone (hGH) antagonist B2036 combines a single amino acid substitution impairing receptor binding site 2 (G120K) with eight additional amino acid substitutions that improve binding site 1 affinity. This hGH antagonist is being tested for treating pathologies linked to excess hGH levels. B2036-PEG is a polyethylene glycol (PEG) conjugated form of B2036 that has an increased half-life due to reduced renal clearance. It is currently in phase III trials for acromegaly. Human GH is also able to bind to the receptor of prolactin (PRLR). Since activation of PRLR can promote an array of pathological states (reproduction disorders, breast cancer), the ability of B2036-PEG to interact with the PRLR had to be determined. In this study, we compared four hGH antagonists (G120K, G120K-PEG, B2036 and B2036-PEG) in three bioassays: proliferation of rat Nb2 cells, binding to the human PRLR and activation of human PRLR-mediated signaling in a cell line stably expressing this receptor and a luciferase reporter gene. Agonistic and antagonistic properties were characterized. Our data show that B2036-PEG does not bind, activate or antagonize PRLRs, either from rat or human origin. These observations further demonstrate that the eight amino acid substitutions within binding site 1 provide binding specificity directed towards the human GH receptor.

Animals↗

PubMed2006

Follicle luteinization in hyperandrogenic follicles of polycystic ovary syndrome patients undergoing gonadotropin therapy for in vitro fertilization.

CONTEXT: Polycystic ovary syndrome (PCOS) is a reproductive disorder of ovarian hyperandrogenism and insulin resistance characterized by abnormal luteinization of small follicles. After exposure to GnRH analog/FSH stimulation for in vitro fertilization (IVF), however, it is unclear whether such PCOS follicles remain abnormally luteinized during the resumption of oocyte maturation in vivo. OBJECTIVE: The aim of this study was to determine whether PCOS follicles exposed to GnRH analog/FSH stimulation for IVF show abnormal luteinization. DESIGN: This study was a prospective cohort. SETTING: The setting was an institutional practice. PATIENTS: Eleven PCOS and 30 normoandrogenic ovulatory women were included. INTERVENTION(S): All subjects received GnRH analog/FSH therapy after basal serum hormone determinations. MAIN OUTCOME MEASURE(S): Follicle fluid aspirated at oocyte retrieval from the first follicle of each ovary was assayed for gonadotropins, steroids, insulin, and glucose. LH receptor mRNA expression was determined in granulosa cells of the same follicle. RESULTS: In PCOS patients with basal hyperandrogenemia and hyperinsulinemia, total oocyte number was increased and follicle diameter was decreased, despite normal maximal serum estradiol levels. Within PCOS follicles, progesterone levels were reduced (P < 0.01), despite comparable bioactive LH and insulin levels and granulosa cell LH receptor mRNA expression; estradiol levels were normal, despite diminished FSH availability (P < 0.004). Elevated androstenedione (P < 0.01), testosterone (P < 0.001), and glucose (P < 0.01) levels also occurred. In PCOS follicles containing mature oocytes, however, elevated androgen levels were accompanied by both normal progesterone concentrations and a normal inverse relationship between glucose depletion and lactate accumulation. CONCLUSION: Hyperandrogenic follicles with mature oocytes from PCOS women receiving GnRH analog/recombinant human FSH therapy for IVF show sufficient glucose utilization for normal luteinization.

Adult↗

PubMed1989

Luteal phase deficiency: abnormal gonadotropin and progesterone secretion patterns.

Luteal phase deficiency (LPD) is a reproductive disorder associated with infertility and spontaneous abortion. This study was undertaken to determine whether LPD might be related to an abnormal pattern of gonadotropin secretion. We tested this hypothesis by evaluating the pattern of pulsatile LH secretion in both the follicular and luteal phases of the menstrual cycle in normal women (n = 21) and women with LPD (n = 20), which was diagnosed on the basis of two out of phase endometrial biopsies. In addition, we sought to determine whether changes in progesterone (P) pulse patterns could account for the decrease in average serum P levels in women with LPD. To this end, we examined the pulse patterns of P and compared these patterns between normal women and those with LPD. Frequent blood sampling was performed in both groups to determine their respective hormone secretion patterns. In the follicular phase, blood samples were obtained every 10 min for 12 h; in the luteal phase the samples were obtained every 10 min for 12 h; in the luteal LH, FSH, and P were assayed in each sample. Pulse detection was performed by an adaptive threshold method of pulse analysis. The LH pulse frequency was significantly higher in the women with LPD than in the normal women in the early follicular phase [P less than 0.05; LPD, 12.8 +/- 1.4 (+/- SE); normal, 8.2 +/- 0.7 pulses/12 h]. LH pulse frequency was similar in the early and late follicular phases in the women with LPD, whereas it was higher in the late follicular phase in normal women. Mean serum FSH levels were not different between groups in both the early and late follicular phases. In the luteal phase the P pulse amplitude and mean serum P level were significantly lower in the LPD group than in the normal women (P less than 0.01). We conclude that 1) a too rapid LH pulse pattern in the early follicular phase may lead to inadequate LH support of the corpus luteum and become manifest as LPD; 2) the mechanism for inadequate P secretion in LPD is decreased P pulse amplitude; 3) the finding of similar serum FSH levels in the two groups in both the early and late follicular phases did not support compromised folliculogenesis as an etiological factor for LPD.

Abortion, Habitual↗

PubMed1989

Reduced bone mass in reproductive-aged women with endometriosis.

Cortical and trabecular bone masses were measured by quantitative computed tomography of the distal radius in 41 women (30 +/- 1 yr) with endometriosis documented by laparoscopy and compared to those in 35 normal women (32 +/- 1 yr). Hormonal status was assessed, and a subset of 10 women with endometriosis underwent evaluation of calcium absorption and excretion. Menstrual cycles were regular in all women, and hormonal medication had not been administered during the 3 months before evaluation. Estradiol and progesterone varied as expected with the day of the cycle. Fasting calcium excretion was normal. Mean cortical and trabecular bone mass values in women with endometriosis were compared to those in the normal women. Women with endometriosis had significantly decreased cortical and trabecular bone mass. Cortical bone mass in normal subjects was 1263 +/- 11 Hounsfield units (HU), whereas in endometriosis, cortical bone mass measured 1133 +/- 16 HU (P less than 0.0001). Normal trabecular bone mass was 226 +/- 10 HU compared to a mean trabecular bone mass of 173 +/- 9 HU (P less than 0.0001) in endometriosis. Despite the decrease in bone mass documented by quantitative computed tomography, hormonal and calcium dynamics were normal and, therefore, did not appear to be significant etiological factors in regard to the bone loss. Since immunological abnormalities have been reported in association with endometriosis, immune factors may play a role in the development of bone loss in endometriosis and might be of pathogenic significance in this reproductive disorder.

Adult↗

PubMed1990

Immunoreactive inhibin alpha-subunit in human serum: implications for radioimmunoassay.

The specificity of the most widely used heterologous RIA for human serum inhibition was examined with regard to its cross-reactivity with the alpha-subunit of inhibin. Using a mixture of recombinant alpha inhibin proteins, including precursor and mature forms, the epitopic specificity of this antibody was localized entirely to the alpha-subunit. Furthermore, varying degrees of alpha inhibin immunoactivity were demonstrated in serum from normal subjects and patients with various reproductive disorders by both Western blot and RIA. These results demonstrate that data obtained using this RIA should be interpreted with caution as to the degree to which they reflect the presence of intact dimeric inhibin vs. alpha inhibin proteins in the circulation.

Antibodies↗

PubMed2006

Characteristics of repeat breeding buffaloes in Nepal.

Repeat breeding is one of the most important reproductive disorders in buffaloes. Its etiology, however, is not well described. The aim of this study was to show the clinical features of repeat breeding buffaloes referred to infertility camps in the southern region of Nepal. Eighty-five buffaloes mated three times or more without conception were clinically examined. Sixty percent of the buffaloes were heifers. Fifty-nine percent of the buffalo cows with repeat breeding were already 10 months or more after calving. Indications of cervicitis were observed in 25% of the repeat breeders. Buffalo cows 12 months or more after calving and heifers in adequate nutritional condition were treated with either GnRH or PGF2alpha, and showed a satisfactory conception rate after treatment. Cows within 12 months post partum and heifers at a relatively younger age were treated with a vitamin/mineral mixture supplement, and this resulted in a moderate conception rate. In conclusion, the major clinical features of repeat breeding buffaloes include a large proportion of heifers, a long interval from calving to treatment, a high incidence of cervicitis, and a high or moderate response to treatment with PGF2alpha and GnRH or vitamin/mineral mixture. More attention needs to be paid to estrous detection and management of mating with bulls.

Age Factors↗

PubMed2006

Formation of follicular cysts in cattle and therapeutic effects of controlled internal drug release.

Follicular cysts in cattle result from excessive growth of the dominant follicle without ovulation and still constitute a major reproductive disorder in this species. One key hormonal characteristic of cows with follicular cysts is the lack of an LH surge, although they have increased plasma estradiol concentrations. Another is a relatively high level of pulsatile secretion of LH that promotes continued growth of the dominant follicle. These LH characteristics seem to result from a functional abnormality in the feedback regulation of LH secretion by estradiol. Treatment with controlled internal drug release devices that increase circulating progesterone levels is effective in resolving follicular cystic conditions by 1) lowering pulsatile LH secretion and 2) restoring the ability of the hypothalamo-pituitary axis to generate an LH surge in response to an increase in circulating estradiol.

Animals↗

PubMed2004

Abnormal bone composition in female juvenile American alligators from a pesticide-polluted lake (Lake Apopka, Florida).

Reproductive disorders have been found in pesticide-exposed alligators living in Lake Apopka, Florida (USA). These disorders have been hypothesized to be caused by exposure to endocrine- disruptive estrogen-like contaminants. The aim of this study was to expand our analysis beyond previous studies by investigating whether bone tissue, known to be affected by sex steroid hormones, is a potential target of endocrine disruptors. Long bones from 16 juvenile female alligators from Lake Apopka (pesticide-contaminated lake) and Lake Woodruff (control lake) were evaluated by peripheral quantitative computed tomography. We observed significant differences in bone composition, with female alligators from the contaminated lake having greater trabecular bone mineral density (BMD), total BMD, and trabecular mineral content compared with females from the control lake (p < 0.05). Increased trabecular and total BMD measurements suggest that juvenile female alligators from Lake Apopka were exposed to contaminants that created an internal environment more estrogenic than that normally observed. This estrogenic environment could be caused by both natural and anthropogenic compounds. Effects on BMD indicate interference with bone homeostasis. We hypothesize that contaminants present in the lake inhibit the natural and continuous resorption of bone tissue, resulting in increased bone mass. Although this is the only study performed to date examining effects of environmental estrogenic compounds on alligator bones, it supports previous laboratory-based studies in rodents. Further, this study is important in demonstrating that the alterations in morphology and physiology induced in free-ranging individuals living in environments contaminated with endocrine-active compounds are not limited to a few systems or tissues; rather, effects can be observed in many tissues affected by these hormones.

Alligators and Crocodiles↗

PubMed2004

Identifying priority health conditions, environmental data, and infrastructure needs: a synopsis of the Pew Environmental Health tracking project.

In this article we describe the methodologic approaches of the Pew Environmental Health Commission at the Johns Hopkins Bloomberg School of Public Health used to identify priority environmental health conditions and develop recommendations to establish a national environmental public health tracking network. We present the results of a survey of public health and environmental practitioners to uncover state and local health tracking needs and priorities. We describe the steps that combined the findings from the state and local health tracking survey and a review of the state of the science on environmental impacts on health to identify priority health end points. Through an examination of national health and health care databases, we then describe trends and public health effects of those diseases that may be linked to the environment. Based on this analysis, respiratory diseases and neurologic diseases are recommended as priorities for tracking. Specific end points recommended for tracking include asthma and chronic respiratory diseases, and chronic neurodegenerative diseases such as multiple sclerosis. Based on trends in reported prevalence, consideration should also be given to developmental disabilities, reproductive disorders, and endocrine/metabolic disorders. Strengthening of current efforts to track cancer and birth defects should also be included as components of a nationwide health tracking network. Finally, we present the recommendations for environmental public health tracking. These recommendations provided the groundwork for the development of the Centers for Disease Control and Prevention's National Environmental Public Health Tracking Progam that now includes 21 states, three cities, and three academic centers throughout the nation.

Centers for Disease Control and Prevention, U.S.↗

PubMed1976

Consumer hazards of plastics.

The modern consumer is exposed to a wide variety of plastic and rubber products in his day to day life: at home, work, school, shopping, recreation and play, and transport. A large variety of toxic sequellae have resulted from untoward exposures by many different routes: oral, dermal, inhalation, and parenteral. Toxic change may result from the plastic itself, migration of unbound components and additives, chemical decomposition or toxic pyrolysis products. The type of damage may involve acute poisoning, chronic organ damage, reproductive disorders, and carcinogenic, mutagenic and teratogenic episodes. Typical examples for all routes are cited along with the activites of Canadian regulatory agencies to reduce both the incidence and severity of plastic-induced disease.

Administration, Oral↗

PubMed1998

Characterization of estrogenicity of phytoestrogens in an endometrial-derived experimental model.

Severe developmental and reproductive disorders in wild animals have been linked to high exposure to persistent environmental chemicals with hormonal activity. These adverse effects of environmental estrogens have raised considerable concern and have received increasing attention. Although numerous chemicals with the capacity to interfere with the estrogen receptor (ER) have been identified, information on their molecular mechanism of action and their relative potency is rather limited. For the endometrium, the lack of information is due to the lack of a suitable experimental model. We investigated the functions of phytoestrogens in an endometrial-derived model, RUCA-I rat endometrial adenocarcinoma cells. The cells were cultured on a reconstituted basement membrane to preserve their functional differentiation and estrogen responsiveness. We assessed the relative binding affinity to the estrogen receptor of the selected phytoestrogens coumestrol, genistein, daidzein, and the putative phytoestrogen mangostin compared to estradiol by a competitive Scatchard analysis. The following affinity ranking was measured: 17beta-estradiol >>> coumestrol > genistein > daidzein >>> mangostin. In addition, we investigated the capacity of these compounds to promote the increased production of complement C3, a well-known estradiol-regulated protein of the rat endometrium. All substances tested increased the production of complement C3, although different concentrations were necessary to achieve equivalent levels of induction compared to estradiol. Mechanistically we were able to demonstrate that the increase of complement C3 production was mediated by primarily increasing its steady-state mRNA level. These findings indicate that RUCA-I cells represent a sensitive model system to elucidate relative potencies and functions of environmental estrogens in an endometrium-derived model.

Adenocarcinoma↗

PubMed1999

Membrane-bound cell surface peptidases in reproductive organs.

Membrane-bound cell surface peptidases including aminopeptidase-N (EC 3.4.11.2), dipeptidyl peptidases IV (EC.3.4.14.5), carboxypeptidase-M (EC 3.4.17.12), neutral endopeptidase (EC 3.4.24.11) and endothelin converting enzyme-1 (EC 3.4.23) were shown to be differently expressed on human ovarian granulosa, theca interna and luteal cells and on endometrial epithelial and stromal cells. These peptidases have their catalytic sites extracellularly and can metabolize biologically active peptides at the cell surface, serving as local regulators of peptide concentrations. In the ovary and endometrium, numerous peptides are considered to be locally produced and play an important role in the follicular growth, ovulation, corpus luteum function, endometrial differentiation and embryo implantation in an autocrine and/or paracrine fashion. The inhibition of aminopeptidase activity by bestatin affected murine follicular growth, steroidogenesis by porcine ovarian cells and progesterone-induced decidualization of human endometrial stromal cells in vivo or in vitro. These findings suggest that membrane-bound peptidases are important regulators of the function and differentiation of the ovarian cells and endometrial cells including embryo. In the near future, the physiological roles of these peptidases will be clarified and clinical use of peptidase inhibitors may be applied to the various reproductive disorders.

Animals↗

PubMed2000

Control of the immunological environment of the uterus.

The uterine immune axis holds the key to solving major problems in female reproductive health, including infertility, many pathologies of pregnancy, and sexually transmitted disease. The molecular determinants of tolerance and immunity in the reproductive tract are now being identified, and the governing principles are similar to those in other mucosal tissues. Cytokines are implicated as pivotal regulators at important 'decision-making' points in each phase of the induction and elicitation of a response. Indeed, the flexibility to deal appropriately with antigens as disparate as infectious micro-organisms, spermatozoa and the conceptus is likely to be attributable to the sophistication of the cytokine network in driving immune deviation. A better understanding of the factors controlling the development of immune activity in the uterus, particularly the significance of the inductive cytokine environment in determining the destiny of T-lymphocyte responses, will assist the rational design of new therapeutic strategies to treat immune-based reproductive disorders.

Cytokines↗

PubMed2002

Searching for Wolbachia (Rickettsiales: Rickettsiaceae) in mosquitoes (Diptera: Culicidae): large polymerase chain reaction survey and new identifications.

Bacteria of the genus Wolbachia constitute a group of intracellular and maternally inherited micro-organisms that are widespread in arthropods, inducing several reproductive disorders such as cytoplasmic incompatibility in their hosts. Considering relevant biological implications related to the presence of Wolbachia in several insect orders, for example its potential role as mechanism for rapid speciation and as vehicle to drive genetic markers in wild populations of vectors of medical and veterinary interest, we carried out an extensive polymerase chain reaction survey to detect Wolbachia in several species of mosquito belonging to genera involved in the transmission of pathogens. Five species out of 26 tested have shown to be infected; for four of them this is the first evidence of the Wolbachia infection. A phylogenetic analysis was also performed, positioning the five Wolbachia strains in the phyletic subdivision B.

Aedes↗

PubMed2001

Dietary soy-phytoestrogens decrease testosterone levels and prostate weight without altering LH, prostate 5alpha-reductase or testicular steroidogenic acute regulatory peptide levels in adult male Sprague-Dawley rats.

Nutritional factors, especially phytoestrogens, have been extensively studied for their potential beneficial effects against hormone-dependent and age-related diseases. The present study describes the short-term effects of dietary phytoestrogens on regulatory behaviors (food/water intake, locomotor activity and body weight), prostate weight, prostate 5alpha-reductase enzyme activity, reproductive hormone levels, and testicular steroidogenic acute regulatory peptide (StAR) levels in adult Sprague-Dawley rats. Animals were fed either a phytoestrogen-rich diet containing approximately 600 microg/g isoflavones (as determined by HPLC) or a phytoestrogen-free diet. After 5 weeks of consuming these diets, plasma phytoestrogen levels were 35 times higher in animals fed the phytoestrogen-rich vs phytoestrogen-free diets. Body and prostate weights were significantly decreased in animals fed the phytoestrogen-rich diet vs the phytoestrogen-free fed animals; however, no significant change in prostate 5alpha-reductase enzyme activity was observed between the treatment groups. Locomotor activity levels were higher in the phytoestrogen-rich vs the phytoestrogen-free animals during the course of the treatment interval. Plasma testosterone and androstenedione levels were significantly lower in the animals fed the phytoestrogen-rich diet compared with animals fed the phytoestrogen-free diet. However, there were no significant differences in plasma LH or estradiol levels between the diet groups. Testicular StAR levels were not significantly different between the phytoestrogen-rich vs the phytoestrogen-free fed animals. These results indicated that consumption of dietary phytoestrogens resulting in very high plasma isoflavone levels over a relatively short period can significantly alter body and prostate weight and plasma androgen hormone levels without affecting gonadotropin or testicular StAR levels. The findings of this study identify the biological actions of phytoestrogens on male reproductive endocrinology and provide insights into the protective effects these estrogen mimics exert in male reproductive disorders such as benign prostatic hyperplasia and prostate cancer.

Animals↗

PubMed2002

Estrogen actions in the ovary revisited.

Estrogens are synonymous with fertility and infertility in mammals. Our knowledge of the biological actions of estrogens, however, is incomplete. Three recent developments have thrown new light on the actions of estrogens in mammalian reproduction that will lead to a greater understanding of their functions. They are (a) the identification of a second estrogen receptor, called ERbeta, (b) the identification of ligand-specific ER coactivators and (c) mouse models with targeted disruption of the genes encoding both ER and the aromatase enzyme. These models provide for the first time animals which are either unable to respond to endogenous or exogenous estrogens (ER 'knockouts'), or can respond to exogenous estrogen but do not make endogenous estrogen (aromatase 'knockout' or ArKO). Furthermore, the ArKO mouse has provided a model to study the effects on the ovary of exogenous estrogens of plant and synthetic origin that are of clinical relevance. The data show that estrogens are essential for fertility but not for survival after birth or for the formation of the reproductive tract. This commentary focuses on the roles of estrogen in folliculogenesis and in the maintenance of the ovarian somatic cell phenotype in the mouse. We also hypothesize that the ERalpha and ERbeta may subserve the proliferative and differentiative actions of estrogen, respectively, within a follicle. In summary, estrogen is obligatory for normal folliculogenesis beyond the antral stage and for the maintenance of the female phenotype of the somatic cells within the ovaries. This clearly demonstrates a major role for sex steroids in somatic cell differentiation in the gonads of eutherian mammals and challenges the central paradigm that the ovary is the default gonad, arising due to the absence of testicular defining signals. Evidence is also provided for the plasticity of the adult female gonad. Understanding the mechanisms of estrogen actions will provide an insight into the regulation of reproductive disorders afflicting women today, notably ovarian dysfunction and the menopause.

Adult↗

PubMed1995

Collaborative work to determine an optimal administration period and optimal parameters for detection of effects on male fertility in rats--male reproductive toxicity study of haloperidol.

Haloperidol, a neuroleptic, was orally administered at 0, 3, 10, 30 and 60 mg/kg/day in a 4-week dosing study, and 0, 3, 10 and 30 mg/kg/day in a 9-week dosing study, to Sprague-Dawley male rats which were then sacrificed for histopathological examination or mated with untreated females. The males in the mating groups were continuously treated during the mating period. Sperm positive females were sacrificed on day 20 of gestation. The males in the histopathology groups were sacrificed after 4- or 9-week dosing and their testes were fixed in Bouin's fluid and sections stained with HE or PAS. The mated males were sacrificed and reproductive organ weights were determined. At 3 mg/kg or more, reduced spontaneous motor activity was observed and body weights were lowered. The absolute weight of testes was decreased with 60 mg/kg in the 4-week dosing study, and was decreased with 10 and 30 mg/kg in the 9-week dosing study. However, the relative weight was increased or showed a tendency to increase. In the 4-week dosing study, decrease in the fertility index with 60 mg/kg and increase in pre-implantation loss with 30 mg/kg or more were noted. However, there were no adverse effects on the copulation index in any of the treated groups. The males given 60 mg/kg showed slight changes in the testes (necrosis of pachytene spermatocytes in seminiferous tubules of stage VII, exfoliation of round spermatids in the lumina and atrophy of Leydig cells) and seminal vesicles (atrophy of epithelial cells). Atrophy of Leydig cells was also observed at 30 mg/kg in the 4-week dosing study. In the 9-week dosing study, neither male reproductive ability nor histopathological parameters were affected by haloperidol up to 30 mg/kg. From the results detailed above, it may be concluded that 4-weeks dosing before mating is suitable for detection of effects of haloperidol on male reproductive ability, and that histopathological changes together provide an optimal parameter for predicting male reproductive disorders.

Animals↗