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Biomedical subjects

S Robert

Publications and source records attributed to S Robert.

At least 19 recordsLinked to original sources

Polycomblike PHD fingers mediate conserved interaction with enhancer of zeste protein.

The products of Polycomb group (PcG) genes are required for the epigenetic repression of a number of important developmental regulatory genes, including homeotic genes. Enhancer of zeste (E(Z)) is a Drosophila PcG protein that previously has been shown to bind directly to another PcG protein, Extra Sex Combs (ESC), and is present along with ESC in a 600-kDa complex in Drosophila embryos. Using yeast two-hybrid and in vitro binding assays, we show that E(Z) binds directly to another PcG protein, Polycomblike (PCL). PCL.E(Z) interaction is shown to be mediated by the plant homeodomain (PHD) fingers domain of PCL, providing evidence that this motif can act as an independent protein interaction domain. An association was also observed between PHF1 and EZH2, human homologs of PCL and E(Z), respectively, demonstrating the evolutionary conservation of this interaction. E(Z) was found to not interact with the PHD domains of three Drosophila trithorax group (trxG) proteins, which function to maintain the transcriptional activity of homeotic genes, providing evidence for the specificity of the interaction of E(Z) with the PCL PHD domain. Coimmunoprecipitation and gel filtration experiments demonstrate in vivo association of PCL with E(Z) and ESC in Drosophila embryos. We discuss the implications of PCL association with ESC.E(Z) complexes and the possibility that PCL may either be a subunit of a subset of ESC.E(Z) complexes or a subunit of a separate complex that interacts with ESC.E(Z) complexes.

Amino Acid Motifs↗

Evidence of a limited role for prolactin in the preparturient activity of confined gilts.

To investigate the role of peripheral prolactin in stimulating the preparturient activity of pigs, 12 cross-bred gilts housed in standard farrowing crates either received orally 10mg of bromocriptine three times per day from day 110 of gestation or served as controls. Jugular blood samples were collected on days 107 and 113 and assayed for prolactin, while the gilts' behaviour was recorded during the last 24h before parturition. Bromocriptine eliminated the preparturient rise in prolactin concentrations (P=0.002). As parturition approached all gilts initially spent less time laying down and more time standing or sitting. The frequency of posture changes also increased as did the incidence of oro-nasal behaviours. These trends were reversed during the final 5-8h before parturition, when the gilts began to lay down for longer periods. The mean concentrations of prolactin on day 113 were correlated with the frequency of posture changes (r=0.70,P=0.015) but not with any other behavioural measure (P>0.10). Bromocriptine had no overall effect on any of the preparturient behaviours (P>0.10) but did reduce the frequency of posture changes 13-16h before parturition (P=0.05). There was a significant interaction between time until parturition and bromocriptine treatment for time spent lying down (P=0.013): bromocriptine delayed the time when the gilts began lying down again as parturition approached. The results suggest that peripheral prolactin plays only a limited role in the preparturient activity of pigs and throws some doubt on its importance in the motivation of nest building in this species.

Journal Article↗

Left ventricular function impairment in pregnancy-induced hypertension.

The changes induced by transient hypertension on cardiac structure and function are unclear. Pregnancy-induced hypertension offers a natural and spontaneous model of this condition. To assess the potential of echocardiographic Doppler to unmask left ventricular function impairment, we studied 28 women aged 26.4 +/- 7.2 years with pregnancy-induced hypertension defined as blood pressure higher than 140/90 mm Hg in the third trimester of pregnancy without a history of hypertension. Twenty normal pregnant women, aged 27.5 +/- 6.4 years, were the controls. Left ventricular diastolic diameter, fractional shortening, E velocity, A velocity, E/A ratio, isovolumetric relaxation time (IRT), isovolumetric contraction time (ICT), ejection time (ET), and the combined index of myocardial performance (Tei index = IRT + ICT/ET), were calculated by echocardiography Doppler 2 to 4 days postpartum. There were statistically significant differences between groups in the following parameters: E/A ratio: 1.3 +/- 0.3 in pregnancy-induced hypertension v 1.5 +/- 0.3 in normal pregnant women (P < .05), IRT: 104 +/- 14 msec v 84 +/- 7 msec (P < .000), and the Tei index: 0.51 +/- 0.15 v 0.35 +/- 0.04 (P < .00), respectively. According to this data pregnancy-induced hypertension evaluated 2 to 4 days after delivery showed left ventricular dysfunction, mainly diastolic. The IRT and the Tei index are the most useful echocardiographic parameters to unmask left ventricular dysfunction in pregnancy-induced hypertension.

Adolescent↗

Effects of repeated cross-fosterings on preweaning behavior and growth performance of piglets and on maternal behavior of sows.

Extensive cross-fostering is widely used in early-weaning units in order to standardize and improve body weight at weaning. However, young suckling piglets develop teat fidelity and repeated cross-fosterings could go against this behavior. This experiment was therefore conducted to compare the behavior and growth of 13 control and 14 fostered litters. Once every 3 d (from d 1 to 16 of lactation), all piglets were weighed and three piglets were switched between two fostered litters. Their unfostered littermates were called residents. Behavior was recorded for 2 h after weighing and(or) adoption and during one nursing period 24 h later. Fights were more frequent (P < 0.05) in treated than in control litters during and between nursings at all ages of adoption except d 1. Most fights occurred between resident and fostered piglets (P < 0.001), except at d 1. Fights during nursing were still more frequent in treated than in control litters 24 h after adoption (P < 0.02), except at d 1 and 16. More piglets had skin lacerations in treated than in control litters except at d 1 (P < 0.05), and scratches were more frequent in fostered than in resident piglets at d 1 (P = 0.07), 7, 13, and 16 (P < 0.01). At all ages except d 1, failed nursings and snaps at piglets were more frequent in fostered than in control litters (P < 0.05), most snaps being directed at adopted piglets (P < 0.001). In fostered litters, sows spent 15 to 30% less time lying on their sides at d 4, 7, 13, and 16 (P < 0.05). Finally, adopted piglets were 13% lighter than controls at weaning (P < 0.001), whereas residents were heavier than adopted piglets (P < 0.05) but lighter than controls (P = 0.1). These data demonstrate that cross-fostering done repeatedly during lactation is stressful for piglets and sows and does not improve body weight at weaning.

Adaptation, Physiological↗

Relationships between individual behavioural traits and post-weaning growth in segregated early-weaned piglets.

Piglets' individual behavioural traits have been studied in the last decade but no report has linked these traits with growth. This experiment was conducted to determine if behavioural traits of segregated early-weaned piglets could be good predictors of their post-weaning growth and, thus, help to predict their adaptation to early weaning. Following segregated early weaning at 17+/-1 days old, 252 piglets were submitted to three tests between 20 and 25 days of age: open-field, reaction to humans and rank order based on competition for a restricted-access feeder. The body weight of each piglet was measured the day before weaning and once a week for the next 4 weeks. A principal component analysis yielded five factors with an Eigenvalue higher than 0.90 that accounted for 81% of the total variation between individuals: reaction to humans (25%), active response to stress (21%), passive response to stress (14%), feeding behaviour (10%) and rank order (9%). Passive reaction to stress was associated with better weight gain during the first week post-weaning (r=0.18; P=0.01), and a positive correlation was found between social status and weight gain during the 4 weeks following weaning (-0.15</=r</=-0.10); P</=0.10). No relation was found between reaction to humans and growth. These results confirm the relationship between rank order and growth in pigs and may suggest that reacting passively to stress could facilitate adaptation to weaning.

Journal Article↗

Feeding motivation and stereotypies in pregnant sows fed increasing levels of fibre and/or food.

Twenty-one multiparous sows were used in a Latin square design, from days 7 to 90 of gestation, to test the effect of fibre and food levels on feeding motivation and feeding-related stereotypies. Treatments were: VHF (very high-fibre, 29% ADF, 50% NDF, 4.5kg/day); HF (high-fibre, 23% ADF, 43% NDF, 3.5kg/day); C (control, 8% ADF, 20% NDF, 2.5kg/day); and control fed ad libitum (CAL). All diets except CAL provided a similar amount of major nutrients on a daily basis and were served in two meals. Each sow was subjected to each treatment for a 21-day period, at the end of which, behavioural observations were made. Two-hour observation periods starting at the afternoon food delivery revealed that sows spent more time eating on VHF and CAL (mean=21.2min) than on HF (13.2min) and C (7.6min) and more time on HF compared to C (p<0.01). When time spent eating was removed from total observation time, the percentage of remaining time spent in stereotypies was lower for VHF (median=17.9%) compared to C (median=49.8%), and lower for CAL (median=6.3%) compared to all other diets (p<0.01). During the period when lights were on (6.00-18.00h), 5min interval scans showed that VHF sows spent more time lying down and less time standing than C sows (p<0.05). Also, CAL sows spent more time lying down than sows on other treatments (p<0.01). During operant conditioning tests (OCT) performed before the afternoon meal and after the morning meal, less rewards were obtained by CAL sows (p<0.01), with no difference between other treatments. In conclusion, no reduction in feeding motivation of sows fed high-fibre diets could be measured by OCT, but very high levels of fibre were effective at reducing stereotypies and activity during the 2h post-feeding. However, these effects were not as marked as those observed with ad libitum feeding.

Journal Article↗

A DEFICIENS homologue is down-regulated during apomictic initiation in ovules of Hieracium.

Hieracium is a member of the Asteraceae family, and contains sexual species in addition to apomictic species that reproduce by apospory and produce seed without fertilization. A homologue of the floral organ-identity gene DEFICIENS (DEF) was isolated from an apomictic line of Hieracium piloselloides (Vill.) following differential display between mature ovules and those initiating autonomous embryogenesis. The gene termed HPDEF has 93% amino acid identity with GDEF2, a DEF homologue isolated from Gerbera hybrida (D. Yu et al., 1999, Plant J. 17: 51-62), another member of the Asteraceae. In-situ analysis showed that early in floral development HPDEF is expressed in stamen and petal primordia, indicating expected B-function activity, according to the ABC model of floral organ identity (J. L. Bowman et al., 1991, Development 112: 1-20; E. S. Coen and E. M. Meyerowitz, 1991, Nature 353: 31-37). However, HPDEF expression was also observed in ovule primordia and expression continued in developing ovules until anthesis, indicating that this gene may have a role in ovule development. Expression of HPDEF was not detected in megaspore mother cells, or in sexual or aposporous embryo sacs. In sexual Hieracium, HPDEF was uniformly expressed throughout the ovule integument until anthesis. In most ovules of the apomict, however, HPDEF expression was transiently down-regulated in a specific zone in the chalazal region where cells initiating aposporous embryo sac formation differentiate. Uniform low-level HPDEF expression was subsequently observed prior to anthesis in ovules from sexual and apomictic plants. HPDEF may be down-regulated as a consequence of apomictic initiation and/or its down-regulation may facilitate progression of apomictic events.

Amino Acid Sequence↗

Polyethylene stent blockage: a porcine model.

BACKGROUND: Endoscopic insertion of biliary stents is a useful treatment for obstructive jaundice resulting from unresectable tumors of the pancreas and biliary tree. The main drawback is the recurrence of jaundice due to clogging. The aim of this study was to establish an experimental model of polyethylene stent clogging in large white pigs. METHODS: A straight polyethylene stent of 5F (group I), 7F (group II) or 10F size (group III) was inserted in the common bile duct. Animals were killed at 2 months, or earlier if physical signs suggesting stent clogging occurred. Chemicophysical analysis of stent deposition combined stereomicroscopy and identification of the contents by means of Fourrier transform infrared spectroscopy. Bacteriologic analyses included identification of aerobic and anaerobic bacteria and measurement of beta-glucuronidase, lecithinase and lipase activities. RESULTS: Physical signs suggesting stent obstruction or death occurred in 8 of 8 animals in group I, 11 of 12 in group II, and 2 of 8 in group III (p < 0.001). The proportion of mucoprotein in the stent contents tended to fall with increasing stent diameter (mean 82%, 58% and 47% for 5F, 7F and 10F, respectively), whereas wheat starch and calcium bilirubinate content increased with increasing stent diameter (9% and 4%, 18% and 10%, and 29% and 23% for 5F, 7 F, and 10F, respectively), although none of these differences were statistically significant. A variety of bacteria were cultured from the stent deposits, including anaerobic strains. Clostridium species were associated with the highest enzyme activities. CONCLUSIONS: In this model the major component of early stent deposits was mucoprotein, and numerous aerobic and anaerobic bacteria were isolated. Formation of calcium bilirubinate was a late phenomenon and poorly related to bacterial enzymatic activities.

Animals↗

Administering exogenous porcine prolactin to lactating sows: milk yield, mammary gland composition, and endocrine and behavioral responses.

Third-parity sows received s.c. injections of sterile water (CTL, n = 12) or 15 mg of recombinant porcine prolactin (pPRL, n = 12) at 0730, 1530, and 2330 from d 2 to 23 of lactation. Litters were standardized to 11 or 12 pigs and were weighed weekly until weaning (d 24). On d 22 of lactation, milk production was estimated, and a milk sample was obtained the next day. Jugular blood samples were collected from sows on d 2, 7, 14, and 21 of lactation. Sows were slaughtered and mammary glands collected at d 24. Injections of pPRL doubled the serum concentrations of prolactin (P < .001) on d 7, 14, and 21 of lactation and decreased IGF-I concentrations on d 14 (P = .07) and 21 (P < .01). Weight, backfat, and milk yield of sows and mean pig weights were not affected by pPRL (P > . 1), yet the mean duration of intervals between nursings was reduced by 4.2 min (P = .06) in pPRL litters (45.9 vs 41.7 min). Dry matter and fat percentages in milk were lower in pPRL sows (P < .01). Weights of parenchymal and extraparenchymal tissues were not altered by pPRL treatment (P > .1). Number of prolactin receptors in parenchymal tissue as well as receptor affinity were similar in both groups (P > .1). Results indicate that virtually all prolactin receptors were saturated in CTL sows. This is probably the reason why additional exogenous prolactin had negligible effects.

Animals↗

Monoacylation of ribonuclease A enables its transport across an in vitro model of the blood-brain barrier.

A major challenge in correcting disorders affecting the central nervous system is to induce blood-brain barrier (BBB) crossing of exogenous biological compounds such as proteins or specific nucleic acid sequences. Fatty acids, due to their high membrane affinity and low toxicity, are good potential candidates to promote this barrier crossing when covalently bound to proteins. In this paper, we report that regiospecific monoacylation of ribonuclease A (RNase A) enables its transport across an in vitro model of the BBB. Myristoylated, palmitoylated and stearoylated RNases A were prepared using reversed micelles as microreactors. All the purified acylated RNases A kept their original enzymatic activity. A single fatty acid moiety was linked to RNase A through the alpha-amino group of its N-terminal lysine as shown by powerful analytical techniques. The ability of monoacylated RNases A to cross an in vitro model of the BBB is strictly dependent on the acyl chain length, which must be at least 16 carbon atoms long.

Acetylation↗

The identification and localization of a human gene with sequence similarity to Polycomblike of Drosophila melanogaster.

The Drosophila Polycomb group (PcG) of genes is required for the epigenetic regulation of a number of important developmental genes, including the homeotic (Hox) genes. The members of this gene family encode proteins that do not share sequence similarity, implying that each plays a unique role in this epigenetic repression mechanism. Polycomblike (Pcl) was the second PcG gene to be identified. We report here the isolation and characterization of a human cDNA, termed PHF1, which encodes a protein with significant sequence similarity to Drosophila Polycomblike (PCL). The region of similarity between PHF1 and PCL includes the two PHD fingers (C4-H-C3 motif), the region between them, and sequences C-terminal to the PHD fingers. PHF1 and PCL are 34% identical over this 258-residue region. PHF1 was mapped to 6p21.3 by fluorescence in situ hybridization. While several genetic diseases that are likely to result from developmental abnormalities map to this region, PHF1 is not a clear candidate gene for any of them.

Amino Acid Sequence↗

Bromocriptine given orally to periparturient of lactating sows inhibits milk production.

Gilts were assigned as controls (CTL, n = 6) or received orally 10 mg of bromocriptine thrice daily from d 110 of gestation until farrowing, (BRPP, n = 7), from d 1 to 6 postpartum (PP) (BRL1, n = 6), from d 7 to 13 PP (BRL2, n = 7), from d 14 to 20 PP (BRL3, n = 6), or from d 21 to 27 PP (BRL4, n = 6). Weights of pigs were recorded at birth, 24 h later, and on d 7, 14, 21, 28, 31 (weaning), 42, and 56 PP. Jugular blood samples were collected from sows on d 109 of gestation and every other day until farrowing, as well as on d 1, 6, 13, 20, and 27 PP. Behavioral observations of sows and litters were taken every 3 min for a 24-h period beginning 48 h after the onset of the treatments. In experimental sows, bromocriptine induced marked reductions in prolactin levels during treatment (P < .001). Compared to CTL sows, concentrations of IGF-I were higher at d 21 (P = .01) and 28 (P = .003) PP in BRL3 and BRL4 sows, respectively. In bromocriptine-treated sows, weight gain of litters was either drastically reduced or abolished (P < .001) during the week of treatment. Treatments also altered significantly the suckling behavior of pigs at all stages studied. Therefore, the present results strongly suggest that prolactin is essential for the initiation and the maintenance of milk production in sows. Results also indicate that prolactin does not seem to be involved in the maintenance of lactational anestrus during a 4-wk lactation.

Administration, Oral↗

Crystallization of monoacylated proteins: influence of acyl chain length.

The crystallization of monoacylated proteins has been investigated using a model system. Acylated derivatives of bovine pancreatic ribonuclease A, differing in their acyl chain lengths (10 to 16 carbon atoms), have been prepared using reverse micelles as microreactors. With one fatty acid moiety per polypeptide chain, covalently attached to the NH2 terminus of the protein, all the modified proteins have similar enzymatic activity and hydrodynamic radius as the native protein. Only the caprylated derivative can give crystals which diffract to high resolution. The resolved structure indicates that: (i) the protein folding is not modified by the chemical modification, (ii) the capryl moiety is not buried within the molecule but available for external interactions. Dynamic light scattering experiments on concentrated solutions show that the protein-protein interactions are dependent on acyl chain length. Proteins with the longest attached chains (14 and 16 carbon atoms) tend to self-associate through acyl group interactions.

Acylation↗

The Drug Utilization Review Network of Quebec.

Drug utilization review programs have been recognized as an effective way to control health care spending while maintaining quality services. This article describes the structure, mandate and activities of Quebec's Drug Utilization Review Network. This 112-member network, which represents 45% of health care facilities in the province, was established to promote the optimal utilization of drugs through the provision of support to pharmacology committees, therapeutic committees and pharmacy departments. The network's main role is to coordinate multi-centre drug utilization studies. Future challenges include maintaining member interest and evaluating the clinical and economic impact of the network's efforts.

Cost Control↗

Renal hemodynamics during norepinephrine and low-dose dopamine infusions in man.

OBJECTIVE: To characterize the effects of pressor doses of norepinephrine and low-dose dopamine (3 micrograms/kg/min) on renal hemodynamics in man, as well as to determine the clinical relevance of combining dopamine with norepinephrine. DESIGN: Prospective, single-blind, randomized study. SETTING: Clinical research unit of a tertiary care hospital. SUBJECTS. Six healthy male volunteers ranging in age between 20 and 28 yrs. INTERVENTIONS: The subjects were assigned randomly to four treatments (1 wk apart) in which renal hemodynamics and electrolyte excretion were assessed. Treatments consisted of 180-min infusions of the following: a) 0.9% sodium chloride (control); b) pressor doses of norepinephrine; c) dopamine at 3 micrograms/kg/min; and d) pressor doses of norepinephrine and dopamine at 3 micrograms/kg/min. Pressor doses of norepinephrine was defined as doses required to increase mean arterial pressure (MAP) by 20 mm Hg. MEASUREMENTS AND MAIN RESULTS: Glomerular filtration rate and renal blood flow were derived from inulin and para-aminohippurate clearances, respectively. Urine output and urine solute excretion were also determined. The mean norepinephrine dose required to increase MAP by 22 +/- 2 mm Hg was 118 +/- 30 ng/kg/min (range 76 to 164). After the addition of dopamine, similar doses of norepinephrine resulted in an MAP increase of 15 +/- 4 mm Hg. Glomerular filtration rate and urine output were comparable under all conditions. The infusion of norepinephrine decreased renal blood flow from 1241 +/- 208 to 922 +/- 143 mL/min/1.73 m2 (p = .03). The addition of dopamine returned renal blood flow to baseline values. The clearance of urine sodium increased significantly with the infusion of dopamine alone (p = .03). All subjects completed the four treatment periods. Adverse events, manifested mostly as palpitations and flushing, were rare and self-limiting. CONCLUSIONS: The addition of dopamine (3 micrograms/kg/min) to pressor doses of norepinephrine normalized renal blood flow in healthy volunteers. These hemodynamic changes were not reflected in urine output and glomerular filtration rate; hence, these monitoring parameters may be unreliable indicators of renal function in the setting of vasopressor therapy. In addition, systemic effects were observed with dopamine (3 micrograms/kg/min), as indicated by a decrease in MAP.

Adult↗

SES differentials in health by age and alternative indicators of SES.

Despite the general persistence and even increase of strong socioeconomic status (SES) differentials in health in the United States, research suggests that SES differentials in health may diminish or become nonexistent at older ages. However, most research has used only limited measures of SES (e.g. education, income), and has not thoroughly investigated intra-elderly age differences in this trend. The current study investigates how SES differentials in health vary by age in the United States, using fairly detailed age categories (through ages 85+), and 2 alternative indicators (home ownership and liquid assets) of a major additional dimension of SES, financial assets, which may be especially important at older ages. We address (a) how strongly financial assets are associated with health, considered both alone and net of education and income; (b) if the health effects of financial assets vary by age; and, more specifically, (c) if their effects are especially pronounced in older age, again considered both alone and net of or relative to education and income. Results show that financial assets, especially liquid assets, considered both alone and net of education and income, are associated with health throughout adulthood and old age, at least until ages 85+. Furthermore, financial assets remain associated with health until quite late in life and become more important relative to education and income at older ages for some measures of health.

Adult↗

Aprotinin.

OBJECTIVE: To review the clinical pharmacology of aprotinin in patients undergoing surgical procedures involving major blood loss, namely, coronary artery bypass graft (CABG). DATA SOURCES: A MEDLINE search was used to identify French- and English-language publications on aprotinin using the indexing terms aprotinin, cardiothoracic surgery, and hemorrhage. The MEDLINE search was supplemented by review of article bibliographies. Data also were obtained from the approved Canadian and US product labels. STUDY SELECTIONS: All abstracts and uncontrolled and controlled clinical trials were reviewed. DATA EXTRACTION: Study design, population, results, and safety information were retained. Efficacy conclusions were drawn from controlled trials. DATA SYNTHESIS: Aprotinin, a serine protease inhibitor isolated from bovine lung tissue, decreases bleeding after cardiac surgery by mechanisms including antifibrinolytic activity and preservation of platelet function. Several trials have shown that aprotinin reduced blood loss and transfusion requirements in patients undergoing CABG. Its use in other surgical procedures involving major blood loss has been reported. Aprotinin is well tolerated, with minor allergic reactions being the most frequently reported adverse effect. Although unsubstantiated, the possibility that aprotinin could create a prothrombic state leading to early graft occlusion and formation of microthrombi in renal and coronary vasculatures is of concern. CONCLUSIONS: Aprotinin is an effective hemostatic agent in CABG. Clear definitions of indications, dosing, safety, and repeated use remain to be investigated thoroughly.

Aprotinin↗

Transcription of the TATA binding protein gene is highly up-regulated during spermatogenesis.

TATA-binding protein (TBP) and its associated factors are required for transcriptional initiation by all three RNA polymerases, and evidence for regulation of their activities during early development has been recently reported. In the present study, we have investigated the regulation of TBP gene expression during male germ cell development. TBP mRNA was found to be increased more than 40-fold in rat and mouse testis and spermatogenic cells relative to somatic tissues. This up-regulation was stage-dependent, occurring specifically in meiotic and postmeiotic cells. Nuclear run-on analysis further demonstrated that transcription of the TBP gene was markedly elevated in the adult mouse testis relative to somatic tissue and prepuberal testis, indicating that transcriptional induction accounts, in large part, for the increased abundance of TBP mRNA in spermatogenic cells. In contrast to TBP mRNA, levels of TBP protein were elevated only 2.5-fold in mouse spermatogenic cells relative to somatic tissues. Polysome gradient analysis suggested that translational repression is an important determining factor in the unexpectedly low ratio of TBP protein-mRNA in male germ cells. These findings raise the possibility that transcriptional induction of TBP during spermatogenesis reflects a cell-specific homeostatic mechanism that maintains TBP protein concentrations at sufficiently high levels throughout male germ cell development.

Animals↗