Alpha-fetoprotein protects the developing female mouse brain from masculinization and defeminization by estrogens

Two clearly opposing views exist on the function of alpha-fetoprotein (AFP), a fetal plasma protein that binds estrogens with high affinity, in the sexual differentiation of the rodent brain. AFP has been proposed to either prevent the entry of estrogens or to actively transport estrogens into the developing female brain. The availability of Afp mutant mice (Afp-/-) now finally allows us to resolve this longstanding controversy concerning the role of AFP in brain sexual differentiation, and thus to determine whether prenatal estrogens contribute to the development of the female brain. Here we show that the brain and behavior of female Afp-/- mice were masculinized and defeminized. However, when estrogen production was blocked by embryonic treatment with the aromatase inhibitor 1,4,6-androstatriene-3,17- dione, the feminine phenotype of these mice was rescued. These results clearly demonstrate that prenatal estrogens masculinize and defeminize the brain and that AFP protects the female brain from these effects of estrogens. © 2006 Nature Publishing Group.

Le rôle de l'hormone anti-müillerienne dans la régulation du fonctionnement de l'ovaire. Revue de la littérature

Anti-mullerian hormone, also called AMH, belongs to the large family of transforming growth factor P. Its role in the sexual differentiation of male fetus is now well known. Recently, AMH has been demonstrated to play an important role in the ovarian function. In fact, AMH seems to regulate the kinetics of follicular development, inhibiting the follicular recruitment and the follicular growth. Thus, this intra-gonadic cybernin could be a decisive determinant of the rapidity of follicular pool exhaustion. Today, some experimental data from the literature suggest that AMH could be a reliable marker of ovarian reserve. This review summarizes the present knowledge about AMH and its role in physiology but also in ovarian pathology.

Genetic disorders and spermatogenesis.

Male infertility affects one man in twenty and a genetic basis seems likely in at least 30% of those men. Genetic regulation of fertility involves the inter-related processes of testicular development, spermatogenesis (involving germ cell mitosis, meiosis and spermatid maturation), and their endocrine and paracrine regulation. In regard to spermatogenesis, particular attention has been given to the Yq11 region, where some spermatogenesis genes ('azoospermia factors') appear to be located. Several candidate genes have been identified but have not been shown to have a defined or essential role in spermatogenesis. Microdeletions of Yq11 are found in approximately 15% of azoospermic or severely oligospermic men. The complexity of the genetic control of male fertility is demonstrated by the evidence for genes involved in spermatogenesis and sexual differentiation on the X chromosome and autosomes. Better understanding of the genetic regulation of normal spermatogenesis will provide new probes for clinical studies; however, at present the majority of spermatogenic failure remains without an identified genetic linkage. The advent of intracytoplasmic sperm injection permits fertility in many previously sterile men and presents the possibility of their transmission of infertility; appropriate counselling is required.

Atresia anal, fístula uretrorretal congênita, bolsa escrotal acessória e pseudo-hermafroditismo em bezerro mestiço

Neste trabalho, é descrito o caso de um bezerro mestiço recém-nascido que apresentava atresia anal tipo 2, fístula uretrorretal congênita, bolsa escrotal bífida e pseudo-hermafroditismo masculino. O principal sinal clínico era a eliminação de fezes por meio do óstio prepucial, uma apresentação incomum em casos de fístula uretrorretal em animais machos. Apesar de o quadro de atresia anal ser relativamente comum nessa espécie, os outros defeitos congênitos encontrados são pouco frequentes.

Escolha de parceiros na adolescência

Mate choice is a component of sexual selection. Trying to understand the patterns of this process, several studies have emphasized the adaptive value of sexual differences and their influence on the assessment of the market value. The pattern for adults presented on the scientific literature, which is based on the preference for certain characteristics, shows that men search a partner who shows high value of fecundity and fertility, thus looking for partners with the ability of being pregnant and nursing their offspring. On the other hand, women look for partners with high socioeconomic status, which is strongly associated with the ability to protect and provide resources for them and their offspring. Surprisingly, there is few works that investigated the mate choice patterns during the beginning of the period of sexual differentiation on the morphological, physiological and behavioral traits. The aim of this study was to investigate mate choice patterns in adolescence in order to describe their preferences and contribute to the understanding of human reproductive behavior. Took part of this research 1,232 students from educational institutions of Natal, Brazil, and visitors to the Scientific, Technological and Cultural Fair UFRN. In the Experimental Study 1, we applied a questionnaire to evaluate the importance of certain characteristics, assessed the degree of romantic involvement and real and ideal partners age preference. In the Experimental Study 2, we did a survey of characteristics considered relevant and evaluate the importance of these characteristics in mate choice. The Experimental Study 3 brought an investigation of mate choice patterns based on self-assessment of adolescents, evaluating ideal partner for a short-term and long-term relationships and actual partner. We found that adolescents are motivated to live romantic experiences. We also observed a preference for partners of similar age to that described for adults. Finally, we found similarities and differences in the preferences for characteristics in real and ideal partners in relation to the adult pattern. In addition, we observed high similarity on the self-assessment and assessment of real and ideal partners. We suggest that in the mate choice, adolescents are similar to young adults in some aspects but not all. Our results show the relevance of the reproductive behavior investigation in this human developmental period and reinforce that further studies should contribute to the understanding of human behavior in terms of ontogenetic development and their evolutionary history.

Neuroendocrine and reproductive aspects of adult male rats exposed neonatally to an antiestrogen

The present study was designed to investigate the effects of a single dose of an estrogen antagonist-clomiphene-during neonatal life, on later neuroendocrine system and reproductive performance. Immediately after birth, male pups received clomiphene citrate (s.c.). At adulthood, although testosterone levels and wet weights of reproductive organs were not altered, the treatment induced an increased number of spermatozoa and a delay in the transit time in the cauda epididymis. Additionally, there was impairment of sexual behavior evidenced by a delay in the latencies to the first mount and first intromission. Treated rats also showed decreased dopaminergic and serotonergic neurotransmissions in the hypothalamus and decreased dopaminergic neurotransmission in the striatum. The decreased dopaminergic activity could be related to the lower sexual motivation observed. These results indicate the necessity of preventing exposure to drugs that may impair sexual differentiation, which can compromise later mating success as well as the capacity to generate descendants. (c) 2006 Elsevier B.V. All rights reserved.

Cholinergic responses of seminal vesicles isolated from rats exposed perinatally to hydrocortisone

This study was performed in order to investigate the cholinomimetic response of seminal vesicles isolated from rats treated with hydrocortisone acetate during perinatal life. At the adult phase, the body weight and the wet weight of the seminal vesicle of these animals were unchanged. However, these male rats exhibited a significant reduction in plasma testosterone concentration. A significant increase in the sensitivity of the seminal vesicle to acetylcholine was also observed. Despite this, there was a significant reduction in the maximum contractile response of the organ to this transmitter. These results indicate that exposure to hydrocortisone during the critical period of brain sexual differentiation has a long-term effect on testosterone production of male rats. In addition, physiological levels of cortisone in perinatal life are also essential to support the contractile response pattern of the seminal vesicle to acetylcholine in adult life, probably crucial to the reproductive process. (C) 2003 Elsevier B.V. Ltd. All rights reserved.

Could neonatal testosterone replacement prevent alterations induced by prenatal stress in male rats?

The present study was designed to examine whether testosterone replacement is able to prevent some effects of maternal restraint stress during the period of brain sexual differentiation - on endocrine system and sexual behavior in male rat descendants. Pregnant rats were exposed to restraint stress for 1 h/day from gestational days 18 to 22. At birth, some male pups from these stressed rats received testosterone propionate. The neonatal testosterone replacement was able to prevent the reduction in anogenital distance at 22 days of age observed in pups from stressed pregnant rats as well as prevents the decrease in testosterone levels during the adulthood of these animals. Testosterone replacement in these males also presented an improvement in sexual performance. In this way, testosterone replacement probably through increasing neonatal level of this hormone was able to prevent the later alterations caused by the prenatal stress during the period of brain sexual differentiation. (c) 2005 Published by Elsevier B.V.

5alpha-reductase 2 inhibition impairs brain defeminization of male rats: Reproductive aspects

The present study was carried out to determine whether 5alpha-reductase 2 (5alpha-R2) metabolic pathway plays a key role in brain sexual differentiation. The inhibition of 5alpha-R2 by finasteride (20 mg/kg/day) from gestational day 19 to postnatal day 5 has long-term effects on sexual behavior and reproductive physiology detected only in adult life. Sexual maturation assessed by timing of preputial separation was unchanged. Finasteride-treated males were able to mate with untreated females which became pregnant but exhibited increased rate of pre-implantation loss. The subfertility observed was probably due to abnormally shaped sperm, since the sperm number was not altered. While plasma testosterone was enhanced, LH levels were not changed. The copulatory potential was not affected and all finasteride-treated rats presented male sexual behavior. Despite this, 53% of them showed homosexual behavior when pretreated with estradiol, suggesting an incomplete brain defeminization. These results indicate that 5alpha-R2 acts in brain sexual differentiation of male rats. Moreover, we suggest that 5alpha-R2 not only produces essential metabolites that act together with estradiol in brain sexual differentiation but also protects the brain from the damaging effects of estradiol excess. (c) 2005 Elsevier B.V. All rights reserved.

Copulatory efficiency and fertility in male rats exposed perinatally to flutamide

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Early juvenile development of Armases rubripes (Rathbun 1897) (Crustacea, Brachyura, Sesarmidae) and comments on the morphology of the megalopa and first crab

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Juvenile development and growth patterns in the mud crab Eurytium limosum (Say, 1818) (Decapoda, Brachyura, Xanthidae) under laboratory conditions

The post-larval development of the mud crab Eurytium limosum was studied under laboratory conditions by using the offspring of ovigerous females collected at the Comprido River mangrove, SP, Brazil. The first crab stage is fully described and the juvenile development, until crab stage 10, is examined with emphasis on morphological change, sexual differentiation and growth patterns. The carapace of the first crab stage is nearly square as observed in other xanthids, becoming similar to adults only at stage 15. The sexes can be distinguished from stage four, based on the number of pleopods and their morphology. While the intermoult period increases, the moult percentage decreases at each stage. The abdominal allometric growth is sex-dependent, with males showing a negative (b=0.71) and females an isometric (b=0.95) relative growth pattern. Male gonopods undergo a positive allometric growth, and their shape changes remarkably until sexual maturity. The cheliped dentition can be observed after stage 4. Regardless of sex, most crabs have a molariform right cheliped, which is thought to aid the handling of asymmetric prey such as gastropods.

Perinatal estrogen exposure: Later repercussion on the fertility of rats

The aim of the present study was to investigate the effects of perinatal estrogen exposure in the fertility of rats. Thus, rats were treated with estrogen on the 21st or 22nd day of intra-uterine life or treated with estrogen immediately after birth. It was observed that the testicular descent of males and beginning of puberty of females were advanced in all estrogen-treated groups. The females from estrogen-treated groups showed reduced frequency of estrous in 15 consecutive days of study, and there was an increase in estrous duration. Their fertility also were impaired and a reduction in the number of alive fetuses, as well as enhancement of pre- and postimplantation loss, mainly in the group treated with estrogen on the 21st day of intra-uterine life. However, the alterations observed in the fertility of estrogen-treated male rats were slighter and only females mated with male rats from the group treated with estrogen immediately after birth showed enhanced preimplantation loss. We suggest that the reproductive function is impaired by exposure to estrogen in the perinatal life of rats, and that the mechanisms involved in this effect are distinct for males and females. (C) 1997 Elsevier B.V.

Prenatal testosterone supplementation alters puberty onset, aggressive behavior, and partner preference in adult male rats

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Gene expression in placentation of farm animals: An overview of gene function during development

Eutherian mammals share a common ancestor that evolved into two main placental types, i.e., hemotrophic (e.g., human and mouse) and histiotrophic (e.g., farm animals), which differ in invasiveness. Pregnancies initiated with assisted reproductive techniques (ART) in farm animals are at increased risk of failure; these losses were associated with placental defects, perhaps due to altered gene expression. Developmentally regulated genes in the placenta seem highly phylogenetically conserved, whereas those expressed later in pregnancy are more species-specific. To elucidate differences between hemotrophic and epitheliochorial placentae, gene expression data were compiled from microarray studies of bovine placental tissues at various stages of pregnancy. Moreover, an in silico subtractive library was constructed based on homology of bovine genes to the database of zebrafish - a nonplacental vertebrate. In addition, the list of placental preferentially expressed genes for the human and mouse were collected using bioinformatics tools (Tissue-specific Gene Expression and Regulation [TiGER] - for humans, and tissue-specific genes database (TiSGeD) - for mice and humans). Humans, mice, and cattle shared 93 genes expressed in their placentae. Most of these were related to immune function (based on analysis of gene ontology). Cattle and women shared expression of 23 genes, mostly related to hormonal activity, whereas mice and women shared 16 genes (primarily sexual differentiation and glycoprotein biology). Because the number of genes expressed by the placentae of both cattle and mice were similar (based on cluster analysis), we concluded that both cattle and mice were suitable models to study the biology of the human placenta. (C) 2011 Elsevier B.V. All rights reserved.