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Spermatogenesis is an extraordinarily complex process, regulated by several factors, which leads to the differentiation of spermatogonia into spermatozoa. Among vertebrates, several reports have been focused on the lizard Podarcis sicula, a seasonal breeder and a good model for the study of reproductive processes. The goal of this review is to resume all the available data about systemic and above all local control factors involved in the control of P. sicula testicular activity. During the seasonal reproductive cycle, the variation of the expression levels of these factors determines significant variations that induce the activation or blocking of spermatogenesis. The data supplied in this review, in addition to analyze the current literature regarding the main actors of Podarcis sicula spermatogenesis, will hopefully provide a basic model that can be used for further studies on the intratesticular interaction between molecular factors that control spermatogenesis.

Stolonization in syllid annelids is a unique mode of reproduction among animals. During the breeding season, a structure resembling the adult but containing only gametes, called stolon, is formed generally at the posterior end of the animal. When stolons mature, they detach from the adult and gametes are released into the water column. The process is synchronized within each species, and it has been reported to be under environmental and endogenous control, probably via endocrine regulation. To further understand reproduction in syllids and to elucidate the molecular toolkit underlying stolonization, we generated Illumina RNA-seq data from different tissues of reproductive and nonreproductive individuals of Syllis magdalena and characterized gene expression during the stolonization process. Several genes involved in gametogenesis (ovochymase, vitellogenin, testis-specific serine/threonine-kinase), immune response (complement receptor 2), neuronal development (tyrosine-protein kinase Src42A), cell proliferation (alpha-1D adrenergic receptor), and steroid metabolism (hydroxysteroid dehydrogenase 2) were found differentially expressed in the different tissues and conditions analyzed. In addition, our findings suggest that several neurohormones, such as methyl farnesoate, dopamine, and serotonin, might trigger stolon formation, the correct maturation of gametes and the detachment of stolons when gametogenesis ends. The process seems to be under circadian control, as indicated by the expression patterns of r-opsins. Overall, our results shed light into the genes that orchestrate the onset of gamete formation and improve our understanding of how some hormones, previously reported to be involved in reproduction and metamorphosis processes in other invertebrates, seem to also regulate reproduction via stolonization. This research received funding from the European Union’s (European Atomic Energy Community’s) Seventh Framework Program (FP7/2007–2013; FP7/2007–2011) under grant agreement 227799 to P.A.-C. Sequencing and analyses were conducted with internal MCZ funds to G.G. and with the support of the Center for Systems Biology and the Research Computing group, both from the Faculty of Arts and Sciences (Harvard University), and with internal funds from the Department of Life Sciences (Natural History Museum of London) to AR. One anonymous reviewer and Associate Editor Mandë Holford provided constructive criticism which helped to improve this study.

Fifteen tagged female sea bass Dicentrarchus labrax were sampled weekly from September to April and plasma vitellogenin (VTG), testosterone (T), 17β-estradiol (E2), and two potential maturation inducing steroids (MISs): 17,20β-dihydroxy-4-pregnen-3-one (17,20βP) and 17,20β,21-trihydroxy-4-pregnen-3-one (20βS) assayed. An oocyte sample was obtained via intraovarian cannulation at each sampling time from every female and the stage of development of the most advanced clutch of oocytes determined and related to VTG and hormone plasma levels for each female. The mean number of ovulations per female was 1·75 ± 0·25 when those females that did not present ovulations were excluded and up to 4 ovulations detected in some females. The highest plasma levels of T (c. 6 ng ml-1) were observed during postvitellogenesis and the beginning of maturation while maximum plasma levels of E2 (>5 ng ml-1) were obtained during late vitellogenesis. VTG plasma levels increased throughout vitellogenesis peaking (c. 2·5 mg ml-1) at postvittelogenesis. For the first time significant changes of plasma progestogens were detected in European sea bass during the sexual cycle. The highest plasma level of 17,20βP (c. 1·1 ng ml-1) was observed during postvitellogenesis while the highest level of 20βS (c. 1·4 ng ml-1) coincided with final maturation. These results suggest that 17,20βP and 20βS play a role in the early and final maturation, respectively, in the European sea bass., This studywas supported by EEC (AIR-CT93-1005) and CICYT (MAR96-1859) and by theSpanish Ministry of Education and Culture and British Council through an IntegratedAction grant (HB1997-0072) to M.C. and D.E.K. J.F.A. was supported by the Generalitat Valenciana

Thyroid hormones, thyroxine (T4) and 3,5,3'-triiodothyronine (T3), are produced by the thyroid gland. To synthesize thyroid hormones the thyroid needs iodide. The uptake of iodide as well as the production and secretion of T4 and T3 by the thyroid gland is regulated by thyrotropin (TSH), which is produced by the pituitary. However, most of the biologically active form, T3, is produced from T4 via monodeiodination in peripheral tissues.This reaction is catalyzed by the deiodinases, type I (ID-I) in liver and kidney, and type II (ID-II) in the central nervous system and brown adipose tissue (BAT). T4 and T3 concentrations differ in the various tissues, like the contribution of T3 produced locally from T4. A large portion of the T3 produced in the liver enters the circulation, whereas T3 produced in the brain and cerebellum is mainly used locally.The production, distribution and transport of thyroid hormones are influenced by several (patho)physiological conditions. In this study we concentrated on the effects of pregnancy on maternal thyroid hormone metabolism. It is well known that thyroid hormones are very important for normal fetal development, especially of the central nervous system. During development thyroid hormones produced by the mother, mainly T4, contribute to the fetal thyroid hormone pools before and also after onset of fetal thyroid function. Insufficient production of maternal thyroid hormones during pregnancy can result in permanent brain damage in the offspring.At the end of gestation the concentrations of T4 and T3 in maternal plasma and tissues have decreased. In order to gain more insight into the effects of pregnancy on the production, distribution, and transport of thyroid hormones in the mother we performed kinetic experiments with T4 and T3 using nonpregnant and near-term pregnant rats (chapter 2). A bolus injection of [125I]T4 and [131I]T3 was given, and blood samples were taken at regular times during the next twenty-four hours.Physiological para-meters of the production, interpool transport, distribution and metabolism of T4 and T3 were estimated by means of a three-compartment model. According to this model three compartments can be distinguished: 1. the plasma; 2. the fast pool; and 3. the slow pool. Liver and kidney are considered to be the main components of the fast pool, whereas skin, muscles and brain belong to the slow pool.In the near-term pregnant rat the production and distribution of T4 remained unchanged. The transport of T4 from plasma to the fast pool was more than tripled, whereas transport to the slow pool remained constant. We suggest that in the near-term pregnant rat available T4 was distributed between the maternal and fetal compartments by means of very fast transport. This hypothesis is based on the fact that it seems unlikely that the transport of T4 to maternal liver and kidney, which are considered to be the main components of the fast pool, will have increased that much in the near-term pregnant rat. This was confirmed by the results of steady-state, double isotopic experiments using nonpregnant and near-term pregnant rats (chapter 3).In this study, the rats received a continuous simultaneous infusion of [125I]T4 and [131I]T3 in order to achieve equilibrium in all tissues. With this method it was possible to calculate the T4 and T3 concentrations, the relative contributions of plasma-derived vs. locally produced T3, the thyroidal T4 and T3 secretion rates, and the plasma-to-tissue ratios for T4 and T3. Indeed, the transport of T4 to liver and kidney, as well as almost all other maternal organs, was diminished. Since the production of T4 remained unchanged this implies that T4 is transported to another compartment, i.e. the feto-placental compartment. This compartment was not measured in these studies.The plasma appearance rate for T3 remained constant in the near-term pregnant rat. This was accomplished by an increase in the secretion of T3 by the thyroid and a decrease in locally produced T3. Less T3 was transported from plasma to liver, kidney, BAT and pituitary. ID-I activity in liver, and ID-II activity in the brain both increased during pregnancy. However, this did not result in an increase in the local conversion of T4 to T3 in these tissues. In the liver the contribution of T3 produced locally remained constant, while in the brain even a decrease was found.The insufficient availability of T4 in maternal tissues, as demonstrated by the lower T4 concentrations, might explain the discrepancy between deiodinase activities and the local production of T3. The transport of T4 to the feto-placental compartment resulted indirectly in a deficiency of T3 in the maternal organs. We can conclude that pregnancy affects maternal thyroid hormone metabolism. The mother has to share the available thyroid hormones, especially T4, with the fetuses.Iodide is an essential element for the synthesis of thyroid hormones. In rats the fetal thyroid is capable of producing thyroid hormones on day 18 of gestation. Iodide is transported across the placenta from the maternal to the fetal circulation. In chapter 4 we assessed iodide uptake by the maternal thyroid, while the iodide uptake by the fetal thyroid was estimated. We measured the in vivo uptake of 125I by the thyroid continuously. By using the specific activity of iodide in the urine we were able to calculate the absolute iodide uptake in the thyroid.Pregnancy resulted in a decrease in the absolute thyroidal iodide uptake. On day 20 of pregnancy the fetal thyroid is already capable of concentrating iodide. However, the difference in absolute iodide uptake by the maternal thyroid, compared to nonpregnant controls, cannot fully be explained by the transport of iodide to the fetal compartment and/or the mammary glands. The decrease in iodide uptake by the maternal thyroid has no impact on the thyroidal production of thyroid hormones.Iodine deficiency can lead to disturbed physical and mental development. In large populations in the world iodine intake is marginally deficient. For this reason a marginal iodine deficiency, instead of the more common severe iodine deficiency, was induced in our rats. We used this model to study the effects of marginal iodine deficiency on iodide metabolism (thyroidal iodide uptake; chapter 4) and thyroid hormone metabolism (kinetic experiments; chapter 5) in near-term pregnant rats.The absolute iodide uptake by the maternal thyroid was not affected by marginal iodine deficiency. The decreased plasma inorganic iodide was compensated by an increase in thyroidal clearance. A similar compensation was not found for the fetus; the uptake of iodide by the fetal thyroid decreased by 50 % during marginal iodine deficiency. During this marginal iodine deficiency plasma T4 and T3 remained constant in nonpregnant as well as near-term pregnant rats. The production rate and the plasma clearance rate for T4 were both decreased.No effects of marginal iodine deficiency on pool sizes and transport rates were found for nonpregnant rats. In the near-term pregnant rat marginal iodine deficiency resulted in a marked decrease in the transport of T4 from plasma to the fast pool. For T3 an increase in the production rate and plasma clearance rate was found for nonpregnant, marginally iodine- deficient rats, while these parameters were slightly decreased in near-term pregnant rats. Marginal iodine deficiency induced a 50 % decrease in the interpool transport rates of T3 between plasma and the fast pool in near-term pregnant rats. The hepatic activity of ID-I was increased as a result of marginal iodine deficiency in nonpregnant as well as near-term pregnant rats.On the basis of the results of thyroid hormone studies in normal pregnant rats (chapter 2 and 3) we suggest that during marginal iodine deficiency less maternal T4 is available for the fetal compartment. Together with the lower uptake of iodide by the fetal thyroid this can lead to diminished levels of thyroid hormone of maternal and fetal origin in the fetal organs. In this case, marginal iodine deficiency will have a negative effect on fetal development, especially of the brain.Another situation which irreversibly affects fetal brain development is maternal hypothyroidism. Two different levels of hypothyroidism were induced in female rats, by giving thyroidectomized rats two different doses of T4 and T3. The effects of hypothyroidism on maternal thyroid hormone metabolism in near-term pregnant rats (kinetic experiment, chapter 6) were studied. Plasma T4 and T3 levels were very low severely hypothyroid animals, whereas only plasma T3 was decreased in the mildly hypothyroid group. Even during this mild hypothyroidism profound alterations in the transport rates of T4 were found compared to intact, pregnant rats. The transport of T4 from plasma to the fast pool was decreased. Therefore, it appears that even during mild hypothyroidism the transport of T4 to the feto-placental compartment is affected.In conclusion: Pregnancy seriously affects the maternal thyroid hormone status. Despite an unchanged thyroidal production of T4, all maternal T4 tissue levels are decreased. Less T4 is available for the mother because of the transport of T4 to the feto-placental compartment. Indirectly this results in a T3-deficiency in most maternal organs. During marginal iodine deficiency and maternal hypothyroidism the transport of maternal T4 to the feto-placental compartment is diminished, whereas during marginal iodine deficiency the availability of iodine for fetal thyroid hormone syn-thesis is also decreased. Eventually this can result in impaired development of the fetal central nervous system.

Thyroid hormones, thyroxine (T4) and 3,5,3'-triiodothyronine (T3), are produced by the thyroid gland. To synthesize thyroid hormones the thyroid needs iodide. The uptake of iodide as well as the production and secretion of T4 and T3 by the thyroid gland is regulated by thyrotropin (TSH), which is produced by the pituitary. However, most of the biologically active form, T3, is produced from T4 via monodeiodination in peripheral tissues.This reaction is catalyzed by the deiodinases, type I (ID-I) in liver and kidney, and type II (ID-II) in the central nervous system and brown adipose tissue (BAT). T4 and T3 concentrations differ in the various tissues, like the contribution of T3 produced locally from T4. A large portion of the T3 produced in the liver enters the circulation, whereas T3 produced in the brain and cerebellum is mainly used locally.The production, distribution and transport of thyroid hormones are influenced by several (patho)physiological conditions. In this study we concentrated on the effects of pregnancy on maternal thyroid hormone metabolism. It is well known that thyroid hormones are very important for normal fetal development, especially of the central nervous system. During development thyroid hormones produced by the mother, mainly T4, contribute to the fetal thyroid hormone pools before and also after onset of fetal thyroid function. Insufficient production of maternal thyroid hormones during pregnancy can result in permanent brain damage in the offspring.At the end of gestation the concentrations of T4 and T3 in maternal plasma and tissues have decreased. In order to gain more insight into the effects of pregnancy on the production, distribution, and transport of thyroid hormones in the mother we performed kinetic experiments with T4 and T3 using nonpregnant and near-term pregnant rats (chapter 2). A bolus injection of [125I]T4 and [131I]T3 was given, and blood samples were taken at regular times during the next twenty-four hours.Physiological para-meters of the production, interpool transport, distribution and metabolism of T4 and T3 were estimated by means of a three-compartment model. According to this model three compartments can be distinguished: 1. the plasma; 2. the fast pool; and 3. the slow pool. Liver and kidney are considered to be the main components of the fast pool, whereas skin, muscles and brain belong to the slow pool.In the near-term pregnant rat the production and distribution of T4 remained unchanged. The transport of T4 from plasma to the fast pool was more than tripled, whereas transport to the slow pool remained constant. We suggest that in the near-term pregnant rat available T4 was distributed between the maternal and fetal compartments by means of very fast transport. This hypothesis is based on the fact that it seems unlikely that the transport of T4 to maternal liver and kidney, which are considered to be the main components of the fast pool, will have increased that much in the near-term pregnant rat. This was confirmed by the results of steady-state, double isotopic experiments using nonpregnant and near-term pregnant rats (chapter 3).In this study, the rats received a continuous simultaneous infusion of [125I]T4 and [131I]T3 in order to achieve equilibrium in all tissues. With this method it was possible to calculate the T4 and T3 concentrations, the relative contributions of plasma-derived vs. locally produced T3, the thyroidal T4 and T3 secretion rates, and the plasma-to-tissue ratios for T4 and T3. Indeed, the transport of T4 to liver and kidney, as well as almost all other maternal organs, was diminished. Since the production of T4 remained unchanged this implies that T4 is transported to another compartment, i.e. the feto-placental compartment. This compartment was not measured in these studies.The plasma appearance rate for T3 remained constant in the near-term pregnant rat. This was accomplished by an increase in the secretion of T3 by the thyroid and a decrease in locally produced T3. Less T3 was transported from plasma to liver, kidney, BAT and pituitary. ID-I activity in liver, and ID-II activity in the brain both increased during pregnancy. However, this did not result in an increase in the local conversion of T4 to T3 in these tissues. In the liver the contribution of T3 produced locally remained constant, while in the brain even a decrease was found.The insufficient availability of T4 in maternal tissues, as demonstrated by the lower T4 concentrations, might explain the discrepancy between deiodinase activities and the local production of T3. The transport of T4 to the feto-placental compartment resulted indirectly in a deficiency of T3 in the maternal organs. We can conclude that pregnancy affects maternal thyroid hormone metabolism. The mother has to share the available thyroid hormones, especially T4, with the fetuses.Iodide is an essential element for the synthesis of thyroid hormones. In rats the fetal thyroid is capable of producing thyroid hormones on day 18 of gestation. Iodide is transported across the placenta from the maternal to the fetal circulation. In chapter 4 we assessed iodide uptake by the maternal thyroid, while the iodide uptake by the fetal thyroid was estimated. We measured the in vivo uptake of 125I by the thyroid continuously. By using the specific activity of iodide in the urine we were able to calculate the absolute iodide uptake in the thyroid.Pregnancy resulted in a decrease in the absolute thyroidal iodide uptake. On day 20 of pregnancy the fetal thyroid is already capable of concentrating iodide. However, the difference in absolute iodide uptake by the maternal thyroid, compared to nonpregnant controls, cannot fully be explained by the transport of iodide to the fetal compartment and/or the mammary glands. The decrease in iodide uptake by the maternal thyroid has no impact on the thyroidal production of thyroid hormones.Iodine deficiency can lead to disturbed physical and mental development. In large populations in the world iodine intake is marginally deficient. For this reason a marginal iodine deficiency, instead of the more common severe iodine deficiency, was induced in our rats. We used this model to study the effects of marginal iodine deficiency on iodide metabolism (thyroidal iodide uptake; chapter 4) and thyroid hormone metabolism (kinetic experiments; chapter 5) in near-term pregnant rats.The absolute iodide uptake by the maternal thyroid was not affected by marginal iodine deficiency. The decreased plasma inorganic iodide was compensated by an increase in thyroidal clearance. A similar compensation was not found for the fetus; the uptake of iodide by the fetal thyroid decreased by 50 % during marginal iodine deficiency. During this marginal iodine deficiency plasma T4 and T3 remained constant in nonpregnant as well as near-term pregnant rats. The production rate and the plasma clearance rate for T4 were both decreased.No effects of marginal iodine deficiency on pool sizes and transport rates were found for nonpregnant rats. In the near-term pregnant rat marginal iodine deficiency resulted in a marked decrease in the transport of T4 from plasma to the fast pool. For T3 an increase in the production rate and plasma clearance rate was found for nonpregnant, marginally iodine- deficient rats, while these parameters were slightly decreased in near-term pregnant rats. Marginal iodine deficiency induced a 50 % decrease in the interpool transport rates of T3 between plasma and the fast pool in near-term pregnant rats. The hepatic activity of ID-I was increased as a result of marginal iodine deficiency in nonpregnant as well as near-term pregnant rats.On the basis of the results of thyroid hormone studies in normal pregnant rats (chapter 2 and 3) we suggest that during marginal iodine deficiency less maternal T4 is available for the fetal compartment. Together with the lower uptake of iodide by the fetal thyroid this can lead to diminished levels of thyroid hormone of maternal and fetal origin in the fetal organs. In this case, marginal iodine deficiency will have a negative effect on fetal development, especially of the brain.Another situation which irreversibly affects fetal brain development is maternal hypothyroidism. Two different levels of hypothyroidism were induced in female rats, by giving thyroidectomized rats two different doses of T4 and T3. The effects of hypothyroidism on maternal thyroid hormone metabolism in near-term pregnant rats (kinetic experiment, chapter 6) were studied. Plasma T4 and T3 levels were very low severely hypothyroid animals, whereas only plasma T3 was decreased in the mildly hypothyroid group. Even during this mild hypothyroidism profound alterations in the transport rates of T4 were found compared to intact, pregnant rats. The transport of T4 from plasma to the fast pool was decreased. Therefore, it appears that even during mild hypothyroidism the transport of T4 to the feto-placental compartment is affected.In conclusion: Pregnancy seriously affects the maternal thyroid hormone status. Despite an unchanged thyroidal production of T4, all maternal T4 tissue levels are decreased. Less T4 is available for the mother because of the transport of T4 to the feto-placental compartment. Indirectly this results in a T3-deficiency in most maternal organs. During marginal iodine deficiency and maternal hypothyroidism the transport of maternal T4 to the feto-placental compartment is diminished, whereas during marginal iodine deficiency the availability of iodine for fetal thyroid hormone syn-thesis is also decreased. Eventually this can result in impaired development of the fetal central nervous system.