Reproduction

Reproduction is a most essential part of life and is subject to dramatic evolutionary pressures. The resulting evolutionary conflicts have led to sex-specific and species-specific solutions which have led to a fascinating diversity of adaptations in all facets of the genesis of life, from gamete design and function via pregnancy to lactation. Currently, we investigate the following main topics of mammalian reproduction.

Functional analysis of the gonads and reproductive components

Understanding ovarian and testicular dynamics during ontogenesis and the annual cycles of breeding and non-breeding seasons is essential to understand gametogenesis and the endocrine control of reproduction. Down-stream events such as puberty, seasonal or non-seasonal sexual activities as well as the fading-out process during senescence help to elucidate species-specific reproductive strategies in general. These also help to identify reproductive failures caused by maladaptation to anthropogenic impacts (resilience). Therefore a particular interest focuses on those wildlife species that are highly endangered or threatened such as elephants, rhinos or carnivores.

Specifically in female mammals with a given gamete pool we study the molecular principles of oocyte-follicle interaction in order to understand how oocyte reserves are exploited after the primordial follicles have been activated.

Studying evolutionary adaptations of reproduction resulted in numerous discoveries of previously unknown peculiarities in many mammalian species, and many fascinating phenomena continue to be unexplained until today. For instance, the luteal function in elephants or the role of persisting corpora lutea in different lynx species remain to be explained.

Comparative gametogenesis and embryogenesis

Not only quantitative reproductive traits, but also the molecular equipment of gametes and the characteristics and physiological functions of their surrounding “supporter” cells such as the Sertoli and Leydig cells for spermatogonia and granulosa and the theca cells for the growing oocytes are governed by evolutionary adaptations. We therefore also study the differential gene expression pattern of spermatogenesis during puberty and in sexually mature individuals faced with dramatic seasonal changes.

In addition, we are very interested in sperm membrane interactions with the secretions of accessory sex glands (the seminal fluid) and their specific interactions with the female genital tract once the sperm cells have started their journey to the oocyte. Detailed analyses of all involved components permit the identification of key molecules which may be relevant to enhance the success of assisted reproduction efforts and which may be a useful indicator to help evaluate qualitative reproductive traits and individual health. Finally, we also study in-vitro feline embryo development and how differential gene expression patterns depend on the application of specific assisted reproduction techniques.

Modes of pregnancies and lactation

Two key traits of mammals are intra-uterine embryogenesis inside the female organism and lactation. An impressive variety of pregnancy modes have evolved in mammals. This diversity has also, in all likelihood, generated many species-specific embryogenesis patterns.

We investigate pregnancy-related molecular mechanisms, fetal development in relation to reproductive health and causes of embryonic failure such as resorption or abortion. The long-term monitoring of gestational events requires innovative tools such as species-specific endocrine tests based on steroid hormone metabolism or non-invasive imaging modalities such as ultrasonography. These tools allow intra-vitam investigations ranging from naked mole rats to elephants and from domestic cats to lions. These studies will in future be complemented by investigations into the function and endocrine control of lactation as a new strategic focus of the IZW.  

Feto-maternal interaction and intra-uterine conflicts

Until today, the main mechanisms of intra-uterine pregnancies are not fully understood. A conceptus is always an allograft which normally would be rejected by the maternal immune system owing to the presence of foreign (paternal) cell receptors.  Only the uterine environment with its capability to create a local, temporary immune tolerance allows the growing fetus to be protected until parturition.  However, the uterus is also a battlefield where embryos fight for limited resources, where maternal selection may take place during fertilisation (cryptic female choice) and where pathogens attempt to utilise the temporary weakness of the maternal immune system by passing through the placental barrier into the tolerated conceptus. These battlefields of evolutionary conflicts are thus of high interest to our understanding of the evolution of mammalian reproduction.

Paternal epigenetic effects

Heritable epigenetic changes, or transgenerational effects, are the result of the fixation of epigenetic markers in the genome of gametes as a result of environmental impacts. The best-studied epigenetic factor so far is the cytosine methylation in certain loci of the DNA, causing inactivation (methylation) or if reversed activation (demethylation) of genes without changing the sequence itself. Past research was focused on maternal epigenetics, neglecting the paternal influence on the next generation. Thus, we focus on the epigenetic memory of male germ cells.

In the wild guinea pig we test whether alterations of environmental conditions lead to changes in the methylation patterns in fathers. We also investigate whether those changes are also detectable in the male offspring, and thus paternally heritable. We further measure possible changes in embryonic gene expression as well as offspring development. We also study differential embryonic expression pattern that may be influenced by specific assisted reproduction techniques such as cell storage or in-vitro culture, with a focus on felid species.

Selected publications

Braun BC, Vargas A, Jewgenow K (2012) The molecular detection of relaxin and its receptor RXFP1 in reproductive tissue of Felis catus and Lynx pardinus during pregnancy. Reproduction 143: 399-410.

Braun BC, Zschockelt L, Dehnhard M, Jewgenow K (2012) Progesterone and estradiol in cat placenta-Biosynthesis and tissue concentration. J Steroid Biochem Mol Biol 132: 295-302.

Carnaby K, Painer J, Söderberg A, Gavier-Widèn D, Göritz F, Dehnhard M, Jewgenow K (2012) Histological and endocrine characterization of the annual luteal activity in Eurasian Lynx (Lynx lynx). Reproduction 144: 477-484.

Dehnhard M, Finkenwirth C, Crosier A, Penfold L, Ringleb J, Jewgenow K (2012) Using PGFM (13,14-dihydro-15-keto-prostaglandin F2α) as a non-invasive pregnancy marker for felids. Theriogenology 77: 1088-1099.

Fuchs B, Müller K, Paasch U, Schiller J (2012) Lysophospholipids: potential Markers of Diseases and Infertility? Mini Rev Med Chem 12: 1.

Hachen A, Jewgenow K, Braun BC (2012) Sequence analysis of feline oviductin and its expression during the estrous cycle in the domestic cat (Felis catus). Theriogenology 77: 539-549.

Hribal R, Jewgenow K, Braun B, Comizzoli P (2012) Influence of culture medium composition on relative mRNA Abundances in domestic cat embryos. Reprod Domest Anim.

Lüders I, Niemuller C, Rich P, Gray C, Hermes R, Göritz F, Hildebrandt TB (2012) Gestating for 22 months: luteal development and pregnancy maintenance in elephants. Proc R Soc Lond B 279: 3687-3696.

Saragusty J, Hermes R, Hofer H, Bouts T, Göritz F, Hildebrandt TB (2012) Male pygmy hippopotamus influence offspring sex ratio. Nature Commun 3: 697.

Schradin C, Eder S, Müller K (2012) Differential investment into testes and sperm production in alternative male reproductive tactics of the African striped mouse (Rhabdomys pumilio). Horm Behav 61: 686–695.

Weyrich A (2012) Preparation of genomic DNA from mamalian sperm. Current Protocols of Molecular Biology, Chapter: Unit 2.12: 1-3.

Yamamoto Y, Yamamoto T, Yuto N, Hildebrandt TB, Lüders I, Wibbelt G, Shiina O, Mouri Y, Sugimura K, Sakamoto S, Kaewmanee S, Nagaoka K, Watanabe G, Taya K (2012) The secretory pattern and source of immunoreactive prolactin in pregnant African (Loxodonta africana) and Asian (Elephas maximus) elephants. J Reprod Develop 58: 105-111.

Drews B, Harmann LM, Beehler LL, Bell B, Drews RF, Hildebrandt TB (2011) Ultrasonographic monitoring of fetal development in unrestrained bonobos (Pan paniscus) at the Milwaukee County Zoo. Zoo Biol 30: 241-253.

Hildebrandt TB, Lüders I, Hermes R, Göritz F, Saragusty J (2011) Reproductive cycle of the elephant. Anim Reprod Sci 124: 176-183.

Lüders I, Taya K, Watanabe G, Yamamoto Y, Yamamoto T, Kaewmanee S, Niemuller C, Gray C, Streich WJ, Hildebrandt TB (2011) Role of the double luteinizing hormone peak, luteinizing follicles, and the secretion of inhibin for dominant follicle selection in Asian elephants (Elephas maximus). Biol Reprod 85: 714-720.

Ringleb J, Waurich R, Wibbelt G, Streich WJ, Jewgenow K (2011) Prolonged storage of epididymal sperm does not affect the fertilization capacity of in vitro matured domestic cat (Felis catus) oocytes when using ICSI. Reprod Fertil Develop 23: 818-825.

Röllig K, Drews B, Göritz F, Hildebrandt TB (2011) The long gestation of the small naked mole-rat (Heterocephalus glaber RUPPELL, 1842) studied with ultrasound biomicroscopy and 3D-ultrasonography. PLoS ONE 6.

Roellig K, Menzies BR, Hildebrandt TB, Goeritz F (2011) The concept of superfetation: a critical review on a 'myth' in mammalian reproduction. Biol Rev 86: 77-95.

Rowe M, Czirjak GA, McGraw KJ, Giraudeau M (2011) Sexual ornamentation reflects antibacterial activity of ejaculates in mallards. Biol Lett 7: 740-742.

Schroeder K, Drews B, Roellig K, Menzies BR, Goeritz F, Hildebrandt TB (2011) In vivo tissue sampling of embryonic resorption sites using ultrasound guided biopsy. Theriogenology 76: 778-784.

Teuber K, Schiller J, Jakop U, Lüpold S, Orledge JM, Blount JD, Royle NJ, Hoodless A, Müller K (2011) MALDI-TOF mass 1 spectrometry as a simple tool to determine the phospholipid / glycolipid composition of sperm: pheasant spermatozoa as one selected example. Anim Reprod Sci 123: 270–278.

Finkenwirth C, Jewgenow K, Meyer HHD, Vargas A, Dehnhard M (2010) PGFM (13,14-dihydro-15-keto-PGF2a) in pregnant and pseudo-pregnant Iberian lynx: A new noninvasive pregnancy marker for felid species. Theriogenology 73: 530-540.

Roellig K, Goeritz F, Fickel J, Hermes R, Hofer H, Hildebrandt TB (2010) Superconception in mammalian pregnancy can be detected and increases reproductive output per breeding season. Nat Commun 1: 78.

Schon J, Blottner S, Gabler C, Fickel J (2010) Vascular endothelial growth factor A is a putative paracrine regulator in seasonally controlled spermatogenesis: Insights from a ruminant model, the roe deer. Growth Factors 28: 202-210.

Scolari S, Müller K, Bittman R, Herrmann A, Müller P (2010) Interaction of mammalian seminal plasma protein PDC-109 with cholesterol ? Implications for a putative CRAC domain. Biochem 49: 9027–9031.

Wagener A, Blottner S, Göritz F, Streich WJ, Fickel J (2010) Circannual changes in the expression of vascular endothelial growth factor in the testis of roe deer (Capreolus capreolus). Anim Reprod Sci 117: 275-278.

Waurich R, Ringleb J, Braun BC, Jewgenow K (2010) Embryonic gene activation in in vitro produced embryos of the domestic cat (Felis catus). Reproduction 140: 531-540.

Weyrich A, Mahr JA, Jauernig O, Göritz F, Fritzenkötter A, Blottner S, Fickel J (2010) Seasonal changes of gene expression in roe deer (Capreolus capreolus) testis measured by expression microarray analysis. Trends Anim Vet Sci J 1: 5-20

Braun BC, Müller K, Lopes CAP, Ringleb J, Jewgenow K (2009) The trefoil domain of porcine zona pellucida: a sperm receptor? Anim Reprod 6: 481-490.

Fuchs B, Jakop U, Göritz F, Hermes R, Hildebrandt T, Schiller J, Müller K (2009) MALDI-TOF "fingerprint" phospholipid mass spectra allow the differentiation between ruminantia and feloideae spermatozoa. Theriogenology 71: 568-575.

Göritz F, Dehnhard M, Hildebrandt TB, Naidenko S V, Vargas A, Martinez F, Lopez-Bao JV, Palomares F, Jewgenow K (2009) Non cat-like ovarian cycle in the eurasian and the Iberian lynx - Ultrasonographical and endocrinological analysis. Reprod Domest Anim 44: 87-91.

Hildebrandt TB, Drews B, Kurz J, Hermes R, Yang S, Göritz F (2009) Pregnancy monitoring in dogs and cats using 3D and 4D ultrasonography. Reprod Domest Anim 44: 125-128.

Jakop U, Fuchs B, Süß R, Wibbelt G, Braun B, Müller K, Schiller J (2009) The solubilisation of boar sperm membranes by different detergents - a microscopic, MALDI TOF MS, 31P NMR and PAGE study on membrane lysis, extraction efficiency, lipid and protein composition. Lipids Health Dis 8: 49.

Jewgenow K, Göritz F, Vargas A, Dehnhard M (2009) Seasonal profiles of ovarian activity in Iberian lynx (Lynx pardinus) based on urinary hormone metabolite analyses. Reprod Domest Anim 44: 92-97.

Lüders I, Hildebrandt TB, Pootoolal J, Rich P, Gray CS, Niemuller CA (2009) Ovarian ultrasonography correlated with fecal progestins and estradiol during the estrous cycle and early pregnancy in giraffes (Giraffa camelopardalis rothschildi). Biol Reprod 81: 989-995.

Lüders I, Niemuller C, Pootoolal J, Rich P, Gray C, Streich WJ, Hildebrandt TB (2009) Sonomorphology of the reproductive tract in male and pregnant and non-pregnant female Rothschild's giraffes (Giraffa camelopardalis rotschildi). Theriogenology 72: 22-31.

Saragusty J, Hermes R, Göritz F, Schmitt DL, Hildebrandt TB (2009) Skewed birth sex ratio and premature mortality in elephants. Anim Reprod Sci 115: 247-254.

Schon J, Neumann S, Wildt DE, Pukazhenthi BS, Jewgenow K (2009) Localization of oestrogen receptors in the epididymis during sexual maturation of the domestic cat. Reprod Domest Anim 44: 294-301.

Vogler BR, Blevins B, Göritz F, Hildebrandt TB, Dehnhard M (2009) Gonadal activity in male and female captive fossas (Cryptoprocta ferox) during the mating season. Reprod Domest Anim 44: 98-102.

Drews B, Hermes R, Göritz F, Gray C, Kurz J, Lueders I, Hildebrandt TB (2008) Early embryo development in the elephant assessed by serial ultrasound examinations. Theriogenology 69: 1120-1128.

Gabler C, Odau S, Müller K, Schon J, Bondzio A, Einspanier R (2008) Exploring cumulus-oocyte-complex-oviductal cell interactions: Gene profiling in the bovine oviduct. J Physiol Pharmacol 59: 29-42.

Müller K, Müller P, Pincemy G, Kurz A, Labbe C (2008) Characterization of sperm plasma membrane properties after cholesterol modification: Consequences for cryopreservation of rainbow trout spermatozoa. Biol Reprod 78: 390-399.

Schon J, Blottner S (2008) Estrogens are involved in seasonal regulation of spermatogenesis and sperm maturation in roe deer (Capreolus capreolus). Gen Comp Endocrinol 159: 257-263.

Fuchs B, Müller K, Göritz F, Blottner S, Schiller J (2007) Characteristic oxidation products of choline plasmalogens are detectable in cattle and roe deer spermatozoa by MALDI-TOF mass spectrometry. Lipids 42: 991-998.

Hildebrandt T, Drews B, Gaeth A P, Göritz F, Hermes R, Schmitt D, Gray C, Rich P, Streich WJ, Short R V, Renfree MB (2007) Foetal age determination and development in elephants. Proc R Soc Lond B 274: 323-331.

Blottner S, Schon J, Jewgenow K (2006) Seasonally activated spermatogenesis is correlated with increased testicular production of testosterone and epidermal growth factor in mink (Mustela vison). Theriogenology 66: 1593-1598.

Blottner S, Stuermer IW (2006) Reproduction of wild Mongolian gerbils bred in the laboratory with respect to generation and season 2. Spermatogenic activity and testicular testosterone concentration. Anim Sci 82: 389-395.

Blottner S, Wagener A, Schon J, Göritz F, Fickel J (2006) Reproductive fitness in roe bucks (Capreolus capreolus): seasonal timing of testis function. Eur J Wildlife Res 52: 9-13.

Göritz F, Neubauer K, Naidenko SV, Fickel J, Jewgenow K (2006) Investigations on reproductive physiology in the male Eurasian lynx (Lynx lynx). Theriogenology 66: 1751-1754.

Lemma A, Bekana M, Schwartz HJ, Hildebrandt T (2006) The effect of body condition on ovarian activity of free ranging tropical jennies (Equus asinus). J Vet Med Series A 53: 1-4.

Neubauer K, Jewgenow K, Fickel J (2006) Follicle-stimulating hormone receptor in felids: Intra- and interspecies variation. Theriogenology 66: 1737-1742.