Neuropeptide signalling shapes feeding and reproductive behaviours in male C. elegans

Sexual dimorphism occurs where different sexes of the same species display differences in characteristics not limited to reproduction. For the nematode Caenorhabditis elegans, in which the complete neuroanatomy has been solved for both hermaphrodites and males, sexually dimorphic features have been observed both in terms of the number of neurons and in synaptic connectivity. In addition, male behaviours, such as food-leaving to prioritise searching for mates, have been attributed to neuropeptides released from sex-shared or sex-specific neurons. In this study, we show that the lury-1 neuropeptide gene shows a sexually dimorphic expression pattern; being expressed in pharyngeal neurons in both sexes but displaying additional expression in tail neurons only in the male. We also show that lury-1 mutant animals show sex differences in feeding behaviours, with pharyngeal pumping elevated in hermaphrodites but reduced in males. LURY-1 also modulates male mating efficiency, influencing motor events during contact with a hermaphrodite. Our findings indicate sex-specific roles of this peptide in feeding and reproduction in C. elegans, providing further insight into neuromodulatory control of sexually dimorphic behaviours.

Early expression of requisite developmental growth hormone imprinted cytochromes P450 and dependent transcription factors

The sexually dimorphic expression of cytochromes P450 (CYP) drug metabolizing enzymes has been reported in all species examined. These sex differences are initially expressed during puberty and are solely regulated by sex differences in the circulating growth hormone (GH) profiles. Once established, however, the different male- and female-dependent CYP isoforms are permanent and immutable, suggesting that adult CYP expression requires imprinting. Since the hormone that regulates an adult function is likely the same hormone that imprints the function, we selectively blocked GH secretion in some newborn male rats while others also received a concurrent physiologic replacement of rat GH. Rats were subsequently challenged, peripubertally, with either a masculine-like episodic GH regimen or the GH vehicle alone. The results demonstrate that episodic GH regulation of male-specific CYP2C11 and CYP3A2, as well as female-predominant CYP2C6, are dependent on developmental GH imprinting. Moreover, the induction and/or activation of major components in the signal transduction pathway regulating the expression of the principal CYP2C11 isoform is obligatorily dependent on perinatal GH imprinting without which CYP2C11 and drug metabolism would be permanently and profoundly suppressed. Since there are additional adult metabolic functions also regulated by GH, pediatric drug therapy that is known to disrupt GH secretion could unintentionally impair adult health.

Estrogen mediates sex differences in preoptic neuropeptide and pituitary hormone production in medaka

The preoptic area (POA) is one of the most evolutionarily conserved regions of the vertebrate brain and contains subsets of neuropeptide-expressing neurons. Here we found in the teleost medaka that two neuropeptides belonging to the secretin family, pituitary adenylate cyclase-activating polypeptide (Pacap) and vasoactive intestinal peptide (Vip), exhibit opposite patterns of sexually dimorphic expression in the same population of POA neurons that project to the anterior pituitary: Pacap is male-biased, whereas Vip is female-biased. Estrogen secreted by the ovary in adulthood was found to attenuate Pacap expression and, conversely, stimulate Vip expression in the female POA, thereby establishing and maintaining their opposite sexual dimorphism. Pituitary organ culture experiments demonstrated that both Pacap and Vip can markedly alter the expression of various anterior pituitary hormones. Collectively, these findings show that males and females use alternative preoptic neuropeptides to regulate anterior pituitary hormones as a result of their different estrogen milieu.

The role of Cyp19a1 in female pathway of a freshwater turtle (Mauremys reevesii) with temperature-dependent sex determination

The molecular mechanism of temperature-dependent sex determination (TSD) in reptiles has been drawn great interest from biologists for several decades. However, which genetic factors are essential for TSD remain elusive, especially for the female sex determination process. Cyp19a1, encodes an enzyme of aromatase catalyzing the conversion of testosterone to estrogen, has been confirmed to modulate steroid hormones involved in the sexual differentiation of many species, but whether it has a critical role in determining the gonadal sexual fate in TSD is still to be elucidated. Here, we identified that Cyp19a1 expression exhibited a temperature-dependent, sexually dimorphic expression pattern, preceding gonadal sex differentiation in a TSD turtle Mauremys reevesii. Cyp19a1 expression in gonads increased dramatically when embryos developed at high female-producing temperatures (FPT), but were extremely low throughout embryogenesis at low male-producing temperatures (MPT). Cyp19a1 expression increased rapidly in response to the temperature shift from MPT to FPT in developing gonads. The sexual phenotype of turtles was successfully reversed by aromatase inhibitor treatment at FPT, and by estrogen treatment at MPT, accompanied with the rapid upregulation of Cyp19a1. These results demonstrate that Cyp19a1 is essential for the female sex determination process in M. reevesii, indicating its vital role in the female pathway of TSD.

Comparison of Gonadal Transcriptomes Uncovers Reproduction-Related Genes with Sexually Dimorphic Expression Patterns in Diodon hystrix

Diodon hystrix is a new and emerging aquaculture species in south China. However, due to the lack of understanding of reproductive regulation, the management of breeding and reproduction under captivity remains a barrier for the commercial aquaculture of D. hystrix. More genetic information is needed to identify genes critical for gonadal development. Here, the first gonadal transcriptomes of D. hystrix were analyzed and 151.89 million clean reads were generated. All reads were assembled into 57,077 unigenes, and 24,574 could be annotated. By comparing the gonad transcriptomes, 11,487 differentially expressed genes were obtained, of which 4599 were upregulated and 6888 were downregulated in the ovaries. Using enrichment analyses, many functional pathways were found to be associated with reproduction regulation. A set of sex-biased genes putatively involved in gonad development and gametogenesis were identified and their sexually dimorphic expression patterns were characterized. The detailed transcriptomic data provide a useful resource for further research on D. hystrix reproductive manipulation.

CYP19A1 (aromatase) dominates female gonadal differentiation in chicken (Gallus gallus) embryos sexual differentiation

Cytochrome P450 Family 19 SubFamily A member 1 (CYP19A1) gene encodes an aromatase which regulates the sexual differentiation in vertebrates by initiating and maintaining 17β-Estradiol (E2) synthesis. Here, we described the spatiotemporal expression pattern of CYP19A1 and its functional role in the embryonic gonad development in amphoteric chickens (Gallus gallus). Results showed that CYP19A1 exhibited a sexually dimorphic expression pattern in female gonads early at embryonic day 5.5 (HH 28) and robustly expressed within the cytoplasm in ovarian medullas. Most importantly, we induced the gonadal sex reversal by ectopically delivering the aromatase inhibitor (AI) or estradiol (E2) into chicken embryos. To further explore the role of CYP19A1 in chicken embryonic sexual differentiation, we successfully developed an effective method to deliver lentiviral particles with CYP19A1 manipulation into chicken embryos via embryonic intravascular injection. The analysis of interference and overexpression of CYP19A1 provided solid evidences that CYP19A1 is both necessary and sufficient to initiate sex differentiation toward female in chicken embryos. Collectively, this work demonstrates that CYP19A1 is a crucial sex differentiation gene in the embryonic development, which provides a foundation for understanding the mechanism of sex determination and differentiation in chickens.